Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach

• Published in: Cancer communications (London, England) England), 2022-10, Vol.42 (10), p.1032-1035
• Main Authors: Zhu, Mengxuan, Chen, Erbao, Yu, Shan, Xu, Chen, Yu, Yiyi, Cao, Xin, Li, Wei, Zhang, Pengfei, Wang, Yan, Lian, Baofeng, Zhang, Shuirong, Qu, Yueting, Huang, Lujia, Shi, Weiwei, Cui, Yuehong, Qian, Li, Liu, Tianshu
• Format: Article
• Language: English
• Subjects: Cell growth; Gallbladder; Gastric cancer; Genes; Letter to the Editor; Letters to the Editor; Liver cancer; Localization; Medical prognosis; Metastasis; Mutation; Survival analysis; Tumors
• ISSN: 2523-3548; 2523-3548
• DOI: 10.1002/cac2.12336

Abbreviations HAC hepatoid adenocarcinoma AFP α-fetoprotein HAS hepatoid adenocarcinoma of the stomach WES whole-exome sequencing AFPGC AFP-producing gastric cancer CNV copy number variation MUC19 mucin 19 KEGG Kyoto encyclopedia of genes and genomes TCGA the cancer genome atlas STAD stomach adenocarcinoma CRC colorectal cancer HCC hepatocellular carcinoma TMB tumor mutation burden NAB neoantigen burden OS overall survival GC gastric cancer DFS disease-free survival SEM standard error of mean Dear Editor, Hepatoid adenocarcinoma (HAC) is a rare pathological subtype of extrahepatic tumor, featured by hepatoid differentiation and α-fetoprotein (AFP)-production [ 1, 2]. Survival analysis of HAS and AFPGC patients showed patients with lower AFP (≤ 20 ng/mL) had a significantly better OS (Supplementary Figure S4B, P = 0.044). [...]both TMB and NAB tended to be negatively correlated with AFP, but the P values were not significant (Supplementary Figure S4C, D). Overexpression of MUC19 slightly increased cell proliferation in HGC27 cells, while it had no significant effect in SNU216 cells (Supplementary Figure S6D, E). [...]the elevated MUC19 significantly promoted cell invasion in both HGC27 and SNU216 cells (Supplementary Figure S6F, Figure 1I). Furthermore, Wnt antagonist XAV939 treatment partially reversed the MUC19-induced cell invasion, whereas AFP levels were not influenced (Supplementary Figure S7E-F). [...]we concluded that MUC19 contributed to the aggressive malignancy phenotypes of GC cells by activating the Wnt/β-catenin signaling pathway.