Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels  

作　　者：Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo 

机构地区：[1]Department of Pathology,Institute of Systems Biomedicine,School of Basic Medical Sciences Peking University,Peking University Third Hospital,Peking University Health Science Center,Beijing 100191,China [2]Department of General Surgery,Peking University Third Hospital,Beijing 100191,China [3]Department of Medical Genetics,Department of Biochemistry and Biophysics,School of Basic Medical Sciences Peking University,Peking University Health Science Center,Beijing 100191,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第4期1344-1360,共17页世界胃肠肿瘤学杂志（英文版）（电子版）

摘　　要：BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete.AIM To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients.METHODS Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic analyses.Subse-quent validations were conducted through spatial transcriptomics and immuno-histochemistry.The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data types.RESULTS CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness.MUC5AC-high cells were found to promote CCA progression through WNT signaling.MUC5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral treatments.MUC13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor immunity.MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils.Utilizing the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple cohorts.CCA samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer prognosis.CONCLUSION Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关 键 词：MUCIN CHOLANGIOCARCINOMA Single-cell RNA sequencing Spatial transcriptomics PROGNOSIS 

分 类 号：R735.8[医药卫生—肿瘤]