Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients

作者全名："Peng, Linglong; Li, Yang; Gu, Haitao; Xiang, Ling; Xiong, Yongfu; Wang, Rong; Zhou, He; Wang, Jijian"

作者地址："[Peng, Linglong; Li, Yang; Gu, Haitao; Wang, Jijian] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Chongqing 400010, Peoples R China; [Xiang, Ling] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Nutr, Chongqing 400010, Peoples R China; [Xiong, Yongfu] North Sichuan Med Coll, Affiliated Hosp, Dept Hepatobiliary Surg, Chengdu 637000, Sichuan, Peoples R China; [Wang, Rong] Sun Yat Sen Univ, Affiliated Hosp 5, Canc Ctr, Dept Oncol, Zhuhai 519000, Peoples R China; [Zhou, He] North Sichuan Med Coll, Affiliated Hosp, Dept Gastrointestinal Surg, Chengdu 637000, Sichuan, Peoples R China"

通信作者："Wang, JJ (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Chongqing 400010, Peoples R China."

来源：AGING-US

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000635686000005

JCR分区：Q2

影响因子：5.2

年份：2021

卷号：13

期号：6

开始页：9043

结束页：9055

文献类型：Article

关键词：colon cancer; mucin 4; tumor mutation burden; tumor-infiltrating immune cells; prognosis

摘要："At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer."

基金机构："Key Medical Research Project of Chongqing Health Planning Commission, China [2017ZDXM012]; Free Exploring Basic Research Project of Science and Technology of Sichuan province, China [21YYJC2058]; Nanchong City [19SHZ0290]; North Sichuan Medical College, Sichuan, China [19SHZ0290]"

基金资助正文："This work was supported by the Key Medical Research Project of Chongqing Health Planning Commission, China [grant number 2017ZDXM012 (to Jijian Wang) ] . The Free Exploring Basic Research Project of Science and Technology of Sichuan province, China [grant number 21YYJC2058 (to He Zhou) ] ; and The Cooperation Project Between Nanchong City and North Sichuan Medical College, Sichuan, China [grant number 19SHZ0290 (to Yongfu Xiong) ] ."