Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm

Katsukura, Nobuhiro; Watanabe, Sho; Shirasaki, Tetsuya; Hibiya, Shuji; Kano, Yoshihito; Akahoshi, Keiichi; Tanabe, Minoru; Kirimura, Susumu; Akashi, Takumi; Kitagawa, Masanobu; Okamoto, Ryuichi; Watanabe, Mamoru; Tsuchiya, Kiichiro

doi:10.1111/cas.14755

Cited by 5 publications

(1 citation statement)

References 38 publications

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“…The yet unknown factors associated with the intestinal pathway induction might in the near future help to guide the development of targeted strategies. Moreover, new markers of the intestinal pathway have been recently reported such as GPA33 [108], which is already evaluated in colorectal cancer for targeted cytotoxic delivery or photoimmunotherapy [109,110].…”

Section: Future Therapeutic Strategiesmentioning

confidence: 99%

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Mas

Lupinacci

Cros

et al. 2021

IJMS

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Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. However, IPMNs and IPMCs include distinct subtypes of precursor (gastric, pancreato-biliary, intestinal) and invasive (tubular, colloid) lesions, also associated to specific characteristics. Notably, consistent data have shown intestinal IPMNs and associated colloid carcinomas, defining the “intestinal pathway”, to be associated with less aggressive features. Genomic specificities have also been uncovered, such as mutations of the GNAS gene, and recent data provide more insights into the mechanisms involved in IPMCs carcinogenesis. This review synthetizes available data on clinical-pathological features and outcomes associated with IPMCs and their subtypes. We also describe known genomic hallmarks of these lesions and summarize the latest data about molecular processes involved in IPMNs initiation and progression to IPMCs. Finally, potential implications for clinical practice and future research strategies are discussed.

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Section: Future Therapeutic Strategiesmentioning

confidence: 99%

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Mas

Lupinacci

Cros

et al. 2021

IJMS

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A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer

Wu,

Liu,

Wang

et al. 2024

Environmental Toxicology

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BackgroundThe metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI.MethodsGenes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein–protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription–quantitative real‐time PCR (RT‐qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes.ResultsThis study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune‐related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells.ConclusionWe distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

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Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics

Deng,

Marino,

Clarke

et al. 2024

Cell Reports Methods

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Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm

Cited by 5 publications

References 38 publications

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer

Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics

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