{"version":"6.9","hitCount":9,"resultList":{"result":[{"id":"PPR1221412","source":"PPR","doi":"10.64898/2026.03.02.709044","title":"Proteomics-Enhanced AI-Digital Pathology in Metastatic Mucinous Colorectal Carcinoma: A Case Report","authorString":"Fülöp L, Szigeti B, Guedes J, Woldmar N, Oskolás H, Marko-Varga M, Appelqvist R, Wieslander E, Pawlowski K, Szadai L, Christersson L, Malm J, Németh IB, Szasz MA, Gil J, Marko-Varga G.","authorList":{"author":[{"fullName":"Fülöp L","firstName":"Livia","lastName":"Fülöp","initials":"L"},{"fullName":"Szigeti B","firstName":"Balázs","lastName":"Szigeti","initials":"B"},{"fullName":"Guedes J","firstName":"Jéssica","lastName":"Guedes","initials":"J"},{"fullName":"Woldmar N","firstName":"Nicole","lastName":"Woldmar","initials":"N"},{"fullName":"Oskolás H","firstName":"Henriett","lastName":"Oskolás","initials":"H"},{"fullName":"Marko-Varga M","firstName":"Matilda","lastName":"Marko-Varga","initials":"M"},{"fullName":"Appelqvist R","firstName":"Roger","lastName":"Appelqvist","initials":"R"},{"fullName":"Wieslander E","firstName":"Elisabet","lastName":"Wieslander","initials":"E"},{"fullName":"Pawlowski K","firstName":"Krysztof","lastName":"Pawlowski","initials":"K"},{"fullName":"Szadai L","firstName":"Leticia","lastName":"Szadai","initials":"L","authorId":{"type":"ORCID","value":"0000-0002-3605-839X"}},{"fullName":"Christersson L","firstName":"Lukas","lastName":"Christersson","initials":"L"},{"fullName":"Malm J","firstName":"Johan","lastName":"Malm","initials":"J"},{"fullName":"Németh IB","firstName":"István Balázs","lastName":"Németh","initials":"IB"},{"fullName":"Szasz MA","firstName":"Marcell","lastName":"Szasz","initials":"MA"},{"fullName":"Gil J","firstName":"Jeovanis","lastName":"Gil","initials":"J"},{"fullName":"Marko-Varga G","firstName":"György","lastName":"Marko-Varga","initials":"G"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0002-3605-839X"}]},"pubYear":"2026","abstractText":"Mucinous colorectal carcinoma (CRC) is a distinct histomorphological subtype characterized by abundant extracellular mucin that may promote immune evasion and chemoresistance. We describe a metastatic mucinous CRC case integrating digital pathology and proteomics to investigate disease progression and therapy resistance. Formalin-fixed paraffin-embedded samples from the primary tumor, peritoneal metastasis, and hepatoduodenal ligament metastasis of a 56-year-old patient were analyzed. Whole-slide imaging with QuPath-based AI enabled detailed histological annotation, while data-independent acquisition mass spectrometry identified over 6,000 proteins. Digital pathology revealed extensive mucin pools, architectural evolution from heterogeneous glandular patterns in the primary tumor to cribriform morphology in advanced metastases, and immune cell exclusion from mucin-rich regions. Proteomics revealed metabolic reprogramming, suppressed antigen presentation, and stage-specific activation of inflammatory, angiogenic, EMT, and PI3K/AKT/mTOR–MYC signaling pathways, consistent with proliferative and therapy-resistant phenotypes.Integration of AI-assisted histopathology with spatial proteomics highlighted the mucin barrier as a key mediator of immune evasion and chemoresistance. These findings support a personalized therapeutic framework targeting mucin-associated mechanisms alongside pathway-directed inhibitors, suggesting that spatial multi-omics may guide precision management strategies for aggressive mucinous colorectal cancer.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2026},"grantsList":{"grant":[{"grantId":"FBKS-2025-18 - (671)","agency":"Berta Kamprad Foundation, Lund, Sweden","orderIn":0}]},"fullTextUrlList":{"fullTextUrl":[{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.64898/2026.03.02.709044"}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"Y","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2026-05-19","firstIndexDate":"2026-05-19","firstPublicationDate":"2026-03-04"},{"id":"PPR944052","source":"PPR","doi":"10.1101/2024.11.20.624298","title":"Signaling downstream of tumor-stroma interaction regulates mucinous colorectal adenocarcinoma apicobasal polarity","authorString":"Pasquier N, Isomursu A, Hamidi H, Mathieu JR, Härkönen J, Follain G, Desterke C, Fusilier Z, Solis J, Belaya I, Kankaanpää P, Barresi V, Cartry J, Bedja S, Jaulin F, Ivaska J.","authorList":{"author":[{"fullName":"Pasquier N","firstName":"Nicolas","lastName":"Pasquier","initials":"N"},{"fullName":"Isomursu A","firstName":"Aleksi","lastName":"Isomursu","initials":"A","authorId":{"type":"ORCID","value":"0000-0001-6006-9163"}},{"fullName":"Hamidi H","firstName":"Hellyeh","lastName":"Hamidi","initials":"H","authorId":{"type":"ORCID","value":"0000-0003-4841-8927"}},{"fullName":"Mathieu JR","firstName":"Jacques R.R.","lastName":"Mathieu","initials":"JR","authorId":{"type":"ORCID","value":"0009-0005-2239-6303"}},{"fullName":"Härkönen J","firstName":"Jouni","lastName":"Härkönen","initials":"J"},{"fullName":"Follain G","firstName":"Gautier","lastName":"Follain","initials":"G","authorId":{"type":"ORCID","value":"0000-0003-0495-9529"}},{"fullName":"Desterke C","firstName":"Christophe","lastName":"Desterke","initials":"C","authorId":{"type":"ORCID","value":"0000-0001-7679-2524"}},{"fullName":"Fusilier Z","firstName":"Zoé","lastName":"Fusilier","initials":"Z"},{"fullName":"Solis J","firstName":"Junel","lastName":"Solis","initials":"J","authorId":{"type":"ORCID","value":"0000-0003-0972-5262"}},{"fullName":"Belaya I","firstName":"Irina","lastName":"Belaya","initials":"I"},{"fullName":"Kankaanpää P","firstName":"Pasi","lastName":"Kankaanpää","initials":"P"},{"fullName":"Barresi V","firstName":"Valeria","lastName":"Barresi","initials":"V"},{"fullName":"Cartry J","firstName":"Jérôme","lastName":"Cartry","initials":"J"},{"fullName":"Bedja S","firstName":"Sabrina","lastName":"Bedja","initials":"S"},{"fullName":"Jaulin F","firstName":"Fanny","lastName":"Jaulin","initials":"F"},{"fullName":"Ivaska J","firstName":"Johanna","lastName":"Ivaska","initials":"J"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0001-6006-9163"},{"type":"ORCID","value":"0000-0001-7594-0679"},{"type":"ORCID","value":"0000-0001-7679-2524"},{"type":"ORCID","value":"0000-0003-0495-9529"},{"type":"ORCID","value":"0000-0003-0972-5262"},{"type":"ORCID","value":"0000-0003-4841-8927"},{"type":"ORCID","value":"0009-0005-2239-6303"}]},"dataLinksTagsList":{"dataLinkstag":["altmetrics"]},"pubYear":"2024","abstractText":"Mucinous colorectal carcinoma (MUC CRC) dissemination into the tumor stroma and metastasis to multiple organs, including the peritoneum, is associated with poor prognosis. Disseminating MUC CRCs exhibit either a conventional ‘apical-in’ or an inverted ‘apical-out’ polarity phenotype that influence patient outcome. Identifying the mechanisms controlling MUC CRC polarity is critical to understand disease progression. Here, we analyze patient-derived MUC CRC xenografts, with apical-in or apical-out polarity, ex vivo or within collagen gels to mimic the peritumoral stroma. Single-cell analyses reveal α2β1-integrin as a key collagen-binding receptor in these models. Collagen–α2β1-integrin interaction activates Src and ERK/MAPK signaling and upregulates the expression of SorLA, an endosomal sorting receptor. SorLA supports apical-in polarity and carcinoma-stroma interactions by promoting integrin recycling to the plasma membrane and HER2/HER3 expression through a positive feedback mechanism. Accordingly, we observe positive correlation between HER2, HER3 and SorLA in patient samples with the highest HER2 expression in apical-in-presenting tissues. Treatment of tumor spheres with clinically relevant HER2/HER3-targeting antibodies reverts sphere polarity and impedes collagen remodeling and adhesion to mouse peritoneum. This SorLA—integrin—HER2/HER3 signaling axis may represent a basis for MUC CRC-patient stratification and shed light on other carcinomas with similar apical-out phenotypes.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2024},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.biorxiv.org/content/biorxiv/early/2024/11/21/2024.11.20.624298.full.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.1101/2024.11.20.624298"}]},"commentCorrectionList":{"commentCorrection":[{"id":"42401587","source":"MED","reference":"Nature communications. \n 2026 Jul;:","type":"Preprint of","note":"Link created based on a title-first author match","orderIn":10001}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"N","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"Y","license":"cc by-nc-nd","hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2024-11-23","firstIndexDate":"2024-11-23","firstPublicationDate":"2024-11-21"},{"id":"PPR801524","source":"PPR","doi":"10.1101/2024.02.01.578409","title":"Single-cell multi-omics reveals insights into differentiation of rare cell types in mucinous colorectal cancer","authorString":"Ladaika CA, Ghobashi AH, Boulton WC, Miller SA, O’Hagan HM.","authorList":{"author":[{"fullName":"Ladaika CA","firstName":"Christopher","lastName":"Ladaika","initials":"CA"},{"fullName":"Ghobashi AH","firstName":"Ahmed","lastName":"Ghobashi","initials":"AH"},{"fullName":"Boulton WC","firstName":"William","lastName":"Boulton","initials":"WC"},{"fullName":"Miller SA","firstName":"Samuel","lastName":"Miller","initials":"SA","authorId":{"type":"ORCID","value":"0000-0002-0106-663X"}},{"fullName":"O’Hagan HM","firstName":"Heather","lastName":"O’Hagan","initials":"HM"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0002-0106-663X"}]},"pubYear":"2024","abstractText":"Neuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EECs), the neuroendocrine cell of the normal colon epithelium, as compared to non-mucinous CRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. Here, single cell multi-omics was used to uncover epigenetic alterations that accompany EEC differentiation, identify STAT3 as a novel regulator of EEC specification, and discover a rare cancer-specific cell type with enteric neuron-like characteristics. Further experiments demonstrated that lysine-specific demethylase 1 (LSD1) and CoREST2 mediate STAT3 demethylation and regulate STAT3 chromatin binding. Knockdown of CoREST2 in an orthotopic xenograft mouse model resulted in decreased primary tumor growth and lung metastases. In culmination, these results provide rationale for new LSD1 inhibitors that target the interaction between LSD1 with STAT3 or CoREST2, which may improve clinical outcomes for patients with mCRC.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2024},"fullTextUrlList":{"fullTextUrl":[{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.1101/2024.02.01.578409"}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"Y","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2024-02-07","firstIndexDate":"2024-02-07","firstPublicationDate":"2024-02-05"},{"id":"PPR709776","source":"PPR","doi":"10.21203/rs.3.rs-3212530/v1","title":"Clinical Treatment Of Colorectal Mucinous Adenocarcinoma Could Be Discriminate From Adenocarcinoma: Genesis And Immune Microenvironment Differences On Transcript Level","authorString":"Liu J, Qiu S, Fu X, Zhou B, Zu R, Lv Z, Li Y, Yang L, Zhou Z.","authorList":{"author":[{"fullName":"Liu J","firstName":"Jianbo","lastName":"Liu","initials":"J"},{"fullName":"Qiu S","firstName":"Siyuan","lastName":"Qiu","initials":"S"},{"fullName":"Fu X","firstName":"Xiaorui","lastName":"Fu","initials":"X"},{"fullName":"Zhou B","firstName":"Bin","lastName":"Zhou","initials":"B"},{"fullName":"Zu R","firstName":"Ruijuan","lastName":"Zu","initials":"R"},{"fullName":"Lv Z","firstName":"Zhaoying","lastName":"Lv","initials":"Z"},{"fullName":"Li Y","firstName":"Yuan","lastName":"Li","initials":"Y"},{"fullName":"Yang L","firstName":"Lie","lastName":"Yang","initials":"L"},{"fullName":"Zhou Z","firstName":"Zongguang","lastName":"Zhou","initials":"Z"}]},"pubYear":"2023","abstractText":"

Background:

Mucinous adenocarcinoma (MC) of colorectal cancer (CRC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. Current treatment of colorectal MC isn't precise enough and the molecular characteristics remain unclear. The study aims to explore the difference between MC and AD of CRC on transcriptome level, for possibility of treating colorectal MC precisely. Methods We accessed the data of CRC patients from The Cancer Genome Atlas (TCGA) database, then we performed differential analysis and weighted gene co-expression network analysis (WGCNA) to identify the differential hub RNAs between colorectal MC and AD. Functional enrichment analysis, RNAs co-expression networks, risk score based on least absolute shrinkage and selection operator (LASSO) regression model and validation in Gene Expression Omnibus (GEO) database, survival analysis were also performed. Finally, differential hub lncRNAs and hub RNA of significant module were validated by quantitative real time PCR (qRT-PCR) among different colon cancer cell lines. Results In total, we found 1680 differential expressed RNAs (DERs) and 4 significant modules (darkred, magenta, lightstellblue1, tan) comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). From the functional enrichment analysis and RNAs co-expression networks, the darkred module was considered as a mucin-associated module, while some others may be associated with unique immune progress. Construction of logistic regression model and calculation of risk score based on differential hub RNAs in darkred module showed acceptable result in both TCGA and GEO data. Survival analysis suggested that many differential hub RNAs were positive and correlated with better survival. Finally, 8 differential hub RNAs in the darkred module (CTD-2547H18.1, CTD-2589M5.4, RP11-234B24.2, LA16c-321D4.2, LINC00261, RP11-25K19.1, COLCA1 and CAPN9) were validated by qRT-PCR. Except for LA16c-321D4.2 and COLCA1, all other RNAs showed higher expression levels in mucin-producing colorectal cell lines (Ls174T, HT-29 and T84). Conclusion This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research into the application of immunotherapy to colorectal MC is needed.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"Research Square","yearOfPublication":2023},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.researchsquare.com/article/rs-3212530/latest.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.21203/rs.3.rs-3212530/v1"}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"Y","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","license":"cc by","versionList":{"version":[{"id":"PPR709776","source":"PPR","firstPublishDate":"2023-08-23","versionNumber":1,"pubTypeList":{"pubType":["preprint"]},"hasEvaluations":"N"}]},"versionNumber":1,"hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2023-08-29","firstIndexDate":"2023-08-31","firstPublicationDate":"2023-08-23"},{"id":"PPR912172","source":"PPR","doi":"10.1101/2024.09.16.613285","title":"Glycosite Mapping and in situ Mass Spectrometry Imaging of MUC2 Glycopeptides via On-slide Digestion with Mucinase StcE","authorString":"Lowery SC, Tran IP, Grimsley G, Stubler R, Mahoney KE, Lucas TM, Charkoftaki G, Santos-Neto A, Varki N, Vasiliou V, Drake RR, Malaker SA.","authorList":{"author":[{"fullName":"Lowery SC","firstName":"Sarah","lastName":"Lowery","initials":"SC","authorId":{"type":"ORCID","value":"0000-0002-1196-5313"}},{"fullName":"Tran IP","firstName":"Isabella","lastName":"Tran","initials":"IP"},{"fullName":"Grimsley G","firstName":"Grace","lastName":"Grimsley","initials":"G"},{"fullName":"Stubler R","firstName":"Rachel","lastName":"Stubler","initials":"R","authorId":{"type":"ORCID","value":"0000-0003-1487-1715"}},{"fullName":"Mahoney KE","firstName":"Keira","lastName":"Mahoney","initials":"KE","authorId":{"type":"ORCID","value":"0000-0003-4561-9838"}},{"fullName":"Lucas TM","firstName":"Taryn","lastName":"Lucas","initials":"TM","authorId":{"type":"ORCID","value":"0000-0002-1697-0939"}},{"fullName":"Charkoftaki G","firstName":"Georgia","lastName":"Charkoftaki","initials":"G","authorId":{"type":"ORCID","value":"0000-0003-2302-8914"}},{"fullName":"Santos-Neto A","firstName":"Alvaro","lastName":"Santos-Neto","initials":"A"},{"fullName":"Varki N","firstName":"Nissi","lastName":"Varki","initials":"N","authorId":{"type":"ORCID","value":"0000-0001-9839-1254"}},{"fullName":"Vasiliou V","firstName":"Vasilis","lastName":"Vasiliou","initials":"V","authorId":{"type":"ORCID","value":"0000-0003-2552-3118"}},{"fullName":"Drake RR","firstName":"Richard","lastName":"Drake","initials":"RR"},{"fullName":"Malaker SA","firstName":"Stacy","lastName":"Malaker","initials":"SA","authorId":{"type":"ORCID","value":"0000-0003-2382-5067"}}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0001-9839-1254"},{"type":"ORCID","value":"0000-0002-1196-5313"},{"type":"ORCID","value":"0000-0002-1697-0939"},{"type":"ORCID","value":"0000-0003-1487-1715"},{"type":"ORCID","value":"0000-0003-2302-8914"},{"type":"ORCID","value":"0000-0003-2382-5067"},{"type":"ORCID","value":"0000-0003-2552-3118"},{"type":"ORCID","value":"0000-0003-4561-9838"}]},"dataLinksTagsList":{"dataLinkstag":["altmetrics"]},"pubYear":"2024","abstractText":"Many cancers are characterized by altered mucin expression and glycosylation, although the mechanistic relationship between tumor glycosylation and disease progression is not well-defined. Herein, our goal was to map specific mucin glycoforms in diseased tissue, enabling correlation of the tumor glycan profile with malignant features. To this end, we developed a workflow implementing on-tissue digestion with mucinase StcE, followed by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography coupled to mass spectrometry (LC-MS). To optimize our workflow, we analyzed four different mucinous carcinomas derived from colon, esophageal, and salivary gland tissue. Using this technique, we deduced the spatial distribution of StcE-generated O-glycopeptides within mucinous tumors using MALDI-IMS. Subsequent LC-MS analyses revealed the identity of different species detected in imaging experiments, in addition to comprehensively characterizing the mucinome and proteome of each tissue. Our coupled MS approach unveiled a striking mucin 2 (MUC2) expression pattern in two colorectal mucinous adenocarcinomas, in which different glycoforms clearly stratified regions within the tumor. Notably, our LC-MS experiments obtained near-complete sequence coverage over the mucin domains of MUC2, enabling glycoproteomic mapping of this canonical mucin in unprecedented depth. MUC2 glycosylation was dominated by the T and Tn antigens, with surprisingly little sialylation detected. However, O-glycans containing mono- and di-O-acetylated sialic acid were detected in low abundance. Finally, we obtained spectral evidence for an endogenous O-acetylated GalNAc, an O-glycan structure not previously reported in the literature. Overall, this proof-of-concept work underscores the potential of this technique to generate new research avenues in oncology and beyond.

Significance Statement

Aberrant mucin expression and glycosylation are hallmarks of cancer, but how these changes promote malignant processes are not well understood. Solid tumors are highly heterogeneous in their cellular and molecular composition, and many advanced spatial techniques have emerged in recent years to study the tumor microenvironment (TME) for better understanding disease progression. Spatially resolved glycoprotein analyses typically detect either the protein or glycan components, but not both. We developed a workflow using a dual mass spectrometry approach to map the location of intact glycopeptides in mucinous tumors, enabled by on-tissue digestion with the mucin-specific protease StcE. Future applications of this method on larger patient cohorts will enhance our understanding of glycans in malignancy, identify disease biomarkers, and define therapeutic targets.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2024},"fullTextUrlList":{"fullTextUrl":[{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.1101/2024.09.16.613285"}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":3,"hasData":"N","hasReferences":"N","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"Y","license":"cc by-nc-nd","hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2024-09-21","firstIndexDate":"2024-09-21","firstPublicationDate":"2024-09-20"},{"id":"PPR674705","source":"PPR","doi":"10.21203/rs.3.rs-3033737/v1","title":"Transcriptomic Landscape Of Colorectal Mucinous Adenocarcinoma Has Similarity With Intestinal Goblet Cells Differentiation","authorString":"Liu J, Qiu S, Fu X, Zhou B, Zu R, Lv Z, Li Y, Yang L, Zhou Z.","authorList":{"author":[{"fullName":"Liu J","firstName":"Jianbo","lastName":"Liu","initials":"J"},{"fullName":"Qiu S","firstName":"Siyuan","lastName":"Qiu","initials":"S"},{"fullName":"Fu X","firstName":"Xiaorui","lastName":"Fu","initials":"X"},{"fullName":"Zhou B","firstName":"Bin","lastName":"Zhou","initials":"B"},{"fullName":"Zu R","firstName":"Ruijuan","lastName":"Zu","initials":"R"},{"fullName":"Lv Z","firstName":"Zhaoying","lastName":"Lv","initials":"Z"},{"fullName":"Li Y","firstName":"Yuan","lastName":"Li","initials":"Y"},{"fullName":"Yang L","firstName":"Lie","lastName":"Yang","initials":"L"},{"fullName":"Zhou Z","firstName":"Zongguang","lastName":"Zhou","initials":"Z"}]},"pubYear":"2023","abstractText":"

Background:

Mucinous adenocarcinoma (MC) of colorectal cancer (CRC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. Current treatment of colorectal MC isn't precise enough and the molecular characteristics remain unclear. Methods We accessed the data of CRC patients from The Cancer Genome Atlas (TCGA) database, then we performed differential analysis and weighted gene co-expression network analysis (WGCNA) to identify the differential hub RNAs between colorectal MC and AD. Functional enrichment analysis, RNAs co-expression networks, risk score based on least absolute shrinkage and selection operator (LASSO) regression model and validation in Gene Expression Omnibus (GEO) database, survival analysis were also performed. Finally, differential hub lncRNAs and hub RNA of significant module were validated by quantitative real time PCR (qRT-PCR) among different colon cancer cell lines. Results In total, we found 1680 differential expressed RNAs (DERs) and 4 significant modules (darkred, magenta, lightstellblue1, tan) comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). From the functional enrichment analysis and RNAs co-expression networks, the darkred module was considered as a mucin-associated module, while others may be associated with other features of colorectal MC. Construction of logistic regression model and calculation of risk score based on differential hub RNAs in darkred module showed acceptable result in both TCGA and GEO data. Survival analysis suggested that many differential hub RNAs were positive and correlated with better survival. Finally, 8 differential hub RNAs in the darkred module (CTD-2547H18.1, CTD-2589M5.4, RP11-234B24.2, LA16c-321D4.2, LINC00261, RP11-25K19.1, COLCA1 and CAPN9) were validated by qRT-PCR. Except for LA16c-321D4.2 and COLCA1, all other RNAs showed higher expression levels in mucin-producing colorectal cell lines (Ls174T, HT-29 and T84). Conclusion The study strengthens the findings of distinct molecular features between MC and AD in CRC and identifies potential marker RNAs making colorectal MC unique from AD. The genesis of colorectal MC may be related to the differentiation fate of intestinal goblet cells.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"Research Square","yearOfPublication":2023},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.researchsquare.com/article/rs-3033737/latest.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.21203/rs.3.rs-3033737/v1"}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"N","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","license":"cc by","versionList":{"version":[{"id":"PPR674705","source":"PPR","firstPublishDate":"2023-06-12","versionNumber":1,"pubTypeList":{"pubType":["preprint"]},"hasEvaluations":"N"}]},"versionNumber":1,"hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2023-06-14","firstIndexDate":"2023-06-14","firstPublicationDate":"2023-06-12"},{"id":"PPR523941","source":"PPR","doi":"10.21203/rs.3.rs-1861874/v1","title":"Establishment and validation of a postoperative predictive model for patients with colorectal mucinous adenocarcinoma","authorString":"Wang P, Song Q, Lu M, Xia Q, Wang Z, Zhao Q, Ma X.","authorList":{"author":[{"fullName":"Wang P","firstName":"Pengchao","lastName":"Wang","initials":"P"},{"fullName":"Song Q","firstName":"Qingyu","lastName":"Song","initials":"Q"},{"fullName":"Lu M","firstName":"Ming","lastName":"Lu","initials":"M"},{"fullName":"Xia Q","firstName":"Qingcheng","lastName":"Xia","initials":"Q"},{"fullName":"Wang Z","firstName":"Zijun","lastName":"Wang","initials":"Z"},{"fullName":"Zhao Q","firstName":"Qinghong","lastName":"Zhao","initials":"Q"},{"fullName":"Ma X","firstName":"Xiang","lastName":"Ma","initials":"X"}]},"pubYear":"2022","abstractText":"

Background:

The aim of this study was to develop comprehensive and effective nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) rates in patients with colorectal mucinous adenocarcinoma (CRMA). MethodsA total of 4711 CRMA patients who underwent radical surgery between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomized into development (n=3,299) and validation (n=1,412) cohorts at a ratio of 7:3 for model development and validation. OS and CSS nomograms were developed using the prognostic factors from the development cohort after multivariable Cox regression analysis. The performance of the nomograms was evaluated using Harrell’s concordance index (C-index), calibration diagrams, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).ResultsThe study included 4,711 patients. Multivariate Cox regression analysis demonstrated that age, tumor size, grade, pT stage, pN stage, M stage, carcinoembryonic antigen, perineural invasion, tumor deposits, regional nodes examined, and chemotherapy were correlated with OS and CSS. Marital status was independently related to OS. In the development and validation cohorts, the C-index of OS was 0.766 and 0.744, respectively, and the C-index of CSS was 0.826 and 0.809, respectively. Calibration curves and ROC curves showed predictive accuracy. DCA showed that the nomograms had excellent potency over the 8th edition of TNM staging system with higher clinical net benefits. Significant differences in OS and CSS were observed among low-, medium-, and high-risk groups.ConclusionsNomograms were developed for the first time to predict personalized 1-, 3-, and 5-year OS and CSS in CRMA postoperative patients. External and internal validation confirmed the excellent discrimination and calibration ability of the nomograms. The nomograms can help clinicians design personalized treatment strategies and assist with clinical decisions.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"Research Square","yearOfPublication":2022},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.researchsquare.com/article/rs-1861874/latest.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.21203/rs.3.rs-1861874/v1"}]},"commentCorrectionList":{"commentCorrection":[{"id":"36192778","source":"MED","reference":"World journal of surgical oncology. \n 2022 Oct;20(1):330","type":"Preprint of","note":"Link created based on a title-first author match","orderIn":10001}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"N","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","license":"cc by","versionList":{"version":[{"id":"PPR523941","source":"PPR","firstPublishDate":"2022-07-26","versionNumber":1,"pubTypeList":{"pubType":["preprint"]},"hasEvaluations":"N"}]},"versionNumber":1,"hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2022-07-27","firstIndexDate":"2022-07-27","firstPublicationDate":"2022-07-26"},{"id":"PPR178802","source":"PPR","doi":"10.21203/rs.3.rs-21102/v2","title":"Survival after Curative Resection for Stage I Colorectal Mucinous Adenocarcinoma","authorString":"Huang L, Luo S, Lai S, Cai Y, Liu Z, Hu H, Zeng Z, Xian CJ, Dong J, Wang L, Kang L.","authorList":{"author":[{"fullName":"Huang L","firstName":"Liang","lastName":"Huang","initials":"L"},{"fullName":"Luo S","firstName":"Shuangling","lastName":"Luo","initials":"S"},{"fullName":"Lai S","firstName":"Sicong","lastName":"Lai","initials":"S"},{"fullName":"Cai Y","firstName":"Yonghua","lastName":"Cai","initials":"Y"},{"fullName":"Liu Z","firstName":"Zhanzhen","lastName":"Liu","initials":"Z"},{"fullName":"Hu H","firstName":"Huanxin","lastName":"Hu","initials":"H"},{"fullName":"Zeng Z","firstName":"Ziwei","lastName":"Zeng","initials":"Z"},{"fullName":"Xian CJ","firstName":"Cory","lastName":"Xian","initials":"CJ"},{"fullName":"Dong J","firstName":"Jianghui","lastName":"Dong","initials":"J"},{"fullName":"Wang L","firstName":"Liping","lastName":"Wang","initials":"L","authorId":{"type":"ORCID","value":"0000-0001-9355-1167"}},{"fullName":"Kang L","firstName":"Liang","lastName":"Kang","initials":"L"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0001-9355-1167"}]},"pubYear":"2020","abstractText":"Abstract

Background: The prognostic value of the mucinous adenocarcinoma histotype on the early stages especially for stage I colorectal cancer (CRC) is still unclear. This study determined the clinicopathologic characteristics and long-term outcome of stage I colorectal mucinous adenocarcinomas (MAC). Methods: Among the total of 503 patients with stage I CRC (56 having MAC and 447 having non-MAC) who underwent radical resection, the correlation between clinicopathological factors and MAC was analyzed. Multivariate analysis was performed to determine whether mucinous histotype itself was an independent prognostic impact in stage I patients. Results: MACs were observed more frequently located in the colon than rectum (p=0.046), more frequently displayed the microsatellite instability (MSI) phenotype (p=0.023) and had a greater frequency of T2 stage (p=0.001). The rate of recurrence was 13.5% and the cancer-specific mortality was 4.3% among all stage I CRC patients. There was no difference in disease-free survival and overall survival between MACs and non-MACs. On multivariate analysis, older age (p=0.030，hazard ratio: 2.62), rectal cancer (p=0.025, hazard ratio: 5.42), lymphovascular invasion (LVI) (p<0.001, hazard ratio: 9.74), and microsatellite stability (MSS) phenotypes (p=0.023, hazard ratio: 4.21) were independently associated to poor survival of stage I CRC. A high carcinoembryonic antigen (CEA) level (p=0.031, hazard ratio: 1.95), rectal cancer (p=0.045, hazard ratio: 1.64), LVI (p=0.002, hazard ratio: 3.95) and MSS phenotypes (p=0.012, hazard ratio: 2.98) were independently related to short disease-free survival of stage I CRC.Conclusions: Compared with non-MAC, MAC patients had more T2 patients and more MSI phenotypes in stage I CRC at presentation, but the mucinous histology is not a significant predictor of recurrence and prognosis in stage I CRC.

","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"Research Square","yearOfPublication":2020},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.researchsquare.com/article/rs-21102/v2.pdf?c=1631858367000"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.21203/rs.3.rs-21102/v2"}]},"commentCorrectionList":{"commentCorrection":[{"id":"35436867","source":"MED","reference":"BMC gastroenterology. 2022 Apr;22(1):192","type":"Preprint of","note":"CrossRef Pre-print loader","orderIn":10001}]},"isOpenAccess":"N","inEPMC":"N","inPMC":"N","hasPDF":"N","hasBook":"N","hasSuppl":"N","citedByCount":0,"hasData":"N","hasReferences":"N","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"N","license":"cc by","versionList":{"version":[{"id":"PPR147303","source":"PPR","firstPublishDate":"2020-04-08","versionNumber":1,"pubTypeList":{"pubType":["preprint"]},"hasEvaluations":"N"},{"id":"PPR178802","source":"PPR","firstPublishDate":"2020-06-22","versionNumber":2,"pubTypeList":{"pubType":["preprint"]},"hasEvaluations":"N"}]},"versionNumber":2,"hasEvaluations":"N","authMan":"N","epmcAuthMan":"N","nihAuthMan":"N","hasTMAccessionNumbers":"N","dateOfCreation":"2020-06-23","firstIndexDate":"2020-06-23","firstPublicationDate":"2020-06-22"},{"id":"PPR588446","source":"PPR","fullTextIdList":{"fullTextId":["PPR588446"]},"doi":"10.1101/2022.12.22.521159","title":"Mutation-induced phenotypic plasticity drives formation of a pro-metastatic tumour-intrinsic niche","authorString":"Bugter JM, El Bouazzaoui L, Küçükköse E, Mills ML, Hong Y, Sprangers J, Jordens I, Kokkinidi D, Plugge S, Venhuizen A, Bosman S, Hageman J, Fenderico N, Gilroy K, Montiel Gonzalez D, van Boxtel R, Suijkerbuijk SJ, Tejpar S, Campbell AD, Sansom OJ, Snippert HJ, Kranenburg O, Maurice MM.","authorList":{"author":[{"fullName":"Bugter JM","firstName":"Jeroen","lastName":"Bugter","initials":"JM","authorId":{"type":"ORCID","value":"0000-0001-9920-2937"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"El Bouazzaoui L","firstName":"Layla","lastName":"El Bouazzaoui","initials":"L","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"},{"affiliation":"Department of Surgical Oncology, Lab Translational Oncology, UMC Utrecht, the Netherlands"}]}},{"fullName":"Küçükköse E","firstName":"Emre","lastName":"Küçükköse","initials":"E","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Surgical Oncology, Lab Translational Oncology, UMC Utrecht, the Netherlands"}]}},{"fullName":"Mills ML","firstName":"Megan","lastName":"Mills","initials":"ML","authorId":{"type":"ORCID","value":"0000-0001-6683-433X"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Oncology, Katholieke Universiteit Leuven, Belgium"}]}},{"fullName":"Hong Y","firstName":"Yourae","lastName":"Hong","initials":"Y","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Sprangers J","firstName":"Joep","lastName":"Sprangers","initials":"J","authorId":{"type":"ORCID","value":"0000-0001-7865-2816"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Jordens I","firstName":"Ingrid","lastName":"Jordens","initials":"I","authorId":{"type":"ORCID","value":"0000-0003-3599-7931"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Kokkinidi D","firstName":"Danai","lastName":"Kokkinidi","initials":"D","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Princes Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands"}]}},{"fullName":"Plugge S","firstName":"Susanna","lastName":"Plugge","initials":"S","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Princes Maxima Centre for Pediatric Oncology, Utrecht, the Netherlands"}]}},{"fullName":"Venhuizen A","firstName":"Anton","lastName":"Venhuizen","initials":"A","authorId":{"type":"ORCID","value":"0000-0002-3197-1307"},"authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, The Netherlands"}]}},{"fullName":"Bosman S","firstName":"Sabine","lastName":"Bosman","initials":"S","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Department of Oncology, Katholieke Universiteit Leuven, Belgium"}]}},{"fullName":"Hageman J","firstName":"Joris","lastName":"Hageman","initials":"J","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Fenderico N","firstName":"Nicola","lastName":"Fenderico","initials":"N","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Division of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, The Netherlands"}]}},{"fullName":"Gilroy K","firstName":"Kathryn","lastName":"Gilroy","initials":"K","authorAffiliationDetailsList":{"authorAffiliation":[{"affiliation":"Oncode Institute and Centre for Molecular Medicine, UMC Utrecht, the Netherlands"}]}},{"fullName":"Montiel Gonzalez D","firstName":"Diego","lastName":"Montiel Gonzalez","initials":"D"},{"fullName":"van Boxtel R","firstName":"Ruben","lastName":"van Boxtel","initials":"R"},{"fullName":"Suijkerbuijk SJ","firstName":"Saskia J.E.","lastName":"Suijkerbuijk","initials":"SJ"},{"fullName":"Tejpar S","firstName":"Sabine","lastName":"Tejpar","initials":"S"},{"fullName":"Campbell AD","firstName":"Andrew","lastName":"Campbell","initials":"AD"},{"fullName":"Sansom OJ","firstName":"Owen","lastName":"Sansom","initials":"OJ"},{"fullName":"Snippert HJ","firstName":"Hugo J.G.","lastName":"Snippert","initials":"HJ"},{"fullName":"Kranenburg O","firstName":"Onno","lastName":"Kranenburg","initials":"O"},{"fullName":"Maurice MM","firstName":"Madelon","lastName":"Maurice","initials":"MM"}]},"authorIdList":{"authorId":[{"type":"ORCID","value":"0000-0001-6683-433X"},{"type":"ORCID","value":"0000-0001-7865-2816"},{"type":"ORCID","value":"0000-0001-9920-2937"},{"type":"ORCID","value":"0000-0002-3197-1307"},{"type":"ORCID","value":"0000-0002-8983-9464"},{"type":"ORCID","value":"0000-0003-3599-7931"}]},"dataLinksTagsList":{"dataLinkstag":["altmetrics","supporting_data"]},"pubYear":"2022","abstractText":"Colorectal cancer (CRC) progression is characterised by a remarkable increase in plasticity and cellular heterogeneity 1,2 . The ability of cells to shift states and adopt mixed lineage potential exacerbates during metastasis and associates with poor patient survival 3 . How these atypical differentiated states emerge and drive cancer progression however has remained unclear. Here, we investigate this issue for BRAF-mutant CRC that commonly arise via the serrated pathway 4 and are linked to poor prognosis via incompletely understood progression steps. Using patient-derived organoids, gene editing and murine tumour models, we show that mutations in RNF43, a regulator of WNT receptor abundance 5 , endow BRAF-mutant CRC with metastatic capacity by driving a non-dividing tumour-intrinsic niche cell (TINC) state that provides growth factor self-sufficiency to the cancer tissue. TINCs are enriched in RNF43 -mutant, mucinous and metastatic samples of human CRC, and ablation of TINCs lead to re-acquired external growth factor dependency during CRC organoid outgrowth. Together, our findings uncover a mechanism by which tumours leverage cellular plasticity to mediate self-organised stem– and niche-cell interactions. Our results argue that formation of a tumour-intrinsic niche is a prerequisite for BRAF-mutant CRC seeding to distant organs and that interference with niche formation may help avoid metastatic relapse.","pubTypeList":{"pubType":["Preprint"]},"bookOrReportDetails":{"publisher":"bioRxiv","yearOfPublication":2022},"grantsList":{"grant":[{"grantId":"91218050","agency":"ZonMw","orderIn":0}]},"fullTextUrlList":{"fullTextUrl":[{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Unpaywall","url":"https://www.biorxiv.org/content/biorxiv/early/2023/04/15/2022.12.22.521159.full.pdf"},{"availability":"Free","availabilityCode":"F","documentStyle":"doi","site":"DOI","url":"https://doi.org/10.1101/2022.12.22.521159"},{"availability":"Open access","availabilityCode":"OA","documentStyle":"html","site":"Europe_PMC","url":"https://europepmc.org/article/PPR/PPR588446"},{"availability":"Open access","availabilityCode":"OA","documentStyle":"pdf","site":"Europe_PMC","url":"https://europepmc.org/api/fulltextRepo?pprId=PPR588446&type=FILE&fileName=EMS158981-pdf.pdf&mimeType=application/pdf"}]},"isOpenAccess":"Y","inEPMC":"Y","inPMC":"N","hasPDF":"Y","hasBook":"N","hasSuppl":"Y","citedByCount":0,"hasData":"Y","hasReferences":"Y","hasTextMinedTerms":"Y","hasDbCrossReferences":"N","hasLabsLinks":"Y","license":"cc by-nc-nd","hasEvaluations":"N","authMan":"N","epmcAuthMan":"Y","nihAuthMan":"N","manuscriptId":"EMS158981","hasTMAccessionNumbers":"Y","tmAccessionTypeList":{"accessionType":["doi"]},"dateOfCreation":"2022-12-24","firstIndexDate":"2022-12-24","fullTextReceivedDate":"2023-04-18","firstPublicationDate":"2022-12-23"}]}}