Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach

• Published in: Cellular oncology (Dordrecht) Vol. 47; no. 2; pp. 677 - 693
• Main Authors: Wei, Jingtao, Ji, Ke, Zhang, Yue, Zhang, Ji, Wu, Xiaojiang, Ji, Xin, Zhou, Kai, Yang, Xuesong, Lu, Hongfeng, Wang, Anqiang, Bu, Zhaode
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2024; Springer Nature B.V
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; c-Met protein; Cancer; Cancer Research; Cell activation; Chemoresistance; Chemotherapy; Copy number; Cytosine; ErbB-2 protein; Exome Sequencing; Female; Fibroblast growth factor receptor 2; Frameshift mutation; Gastric cancer; Gene amplification; Gene Expression Regulation, Neoplastic - drug effects; Gene frequency; Genomics; HGF gene; Humans; Lymphocytes; Male; Middle Aged; Mutation - genetics; Oncology; p53 Protein; Pathology; Retrospective Studies; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Therapeutic targets; Transcriptome - genetics; Transcriptomes; Transcriptomics; Transversion; Treatment Outcome; Hepatoid adenocarcinoma; Genome; Preoperative chemotherapy; Transcriptome
• ISSN: 2211-3428; 2211-3436
• DOI: 10.1007/s13402-023-00892-9

Purpose Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. Methods Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. Results A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53 . In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2 , FGFR2 , MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. Conclusion Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2 , FGFR2 , MET and HGF gene amplification may be potential therapeutic targets for HAS.