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- Title
Mutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment.
- Authors
Yu, Pengfei; Hu, Can; Ding, Guangyu; Shi, Xiaoliang; Xu, Jingli; Cao, Yang; Chen, Xiangliu; Wu, Wei; Xu, Qi; Fang, Jingquan; Huang, Xingmao; Yuan, Shaohua; Chen, Hui; Wang, Zhizheng; Huang, Ling; Pang, Fei; Du, Yian; Cheng, Xiangdong
- Abstract
Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo. 'Gastric cancer metastasis to the ovary is difficult to treat and is not fully understood. Here, the authors characterized mutations in a cohort of matched primary and metastatic disease, and found mutations, including in CLDN18, could predict treatment response to paclitaxel.
- Subjects
TUMOR markers; STOMACH cancer; PACLITAXEL; METASTASIS; OVARIAN follicle; TREATMENT failure; MOLECULAR evolution
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48144-0