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Updated: Dec 27, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant
Ziyu Li1, Xiangyu Gao1, Xinxin Peng2
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Abstract:
Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.
Insights
Biomarkers for gastric cancer neoadjuvant chemotherapy are lacking. This study identifies genetic markers like C10orf71 mutations linked to resistance, and MYC/MDM2 amplifications affecting response, paving the way for precision medicine.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Neoadjuvant chemotherapy is crucial for gastric cancer but underused due to a lack of patient selection biomarkers and resistance understanding.
- Identifying predictive biomarkers is essential to optimize neoadjuvant chemotherapy efficacy in gastric cancer patients.
Purpose of the Study:
- To identify genomic biomarkers associated with response and resistance to neoadjuvant chemotherapy in gastric cancer.
- To explore the impact of neoadjuvant chemotherapy on tumor genetics and the tumor microenvironment.
Main Methods:
- Whole-genome, whole-exome, and RNA sequencing were performed on 84 clinical samples from 35 gastric cancer patients.
- Tumor samples included matched pre- and posttreatment specimens, with patient responses rigorously defined.
Main Results:
- Nonresponse tumors showed increased microsatellite instability and mutation burden.
- C10orf71 mutations were linked to treatment resistance; MYC amplification correlated with sensitivity, while MDM2 amplification indicated resistance.
- Neoadjuvant chemotherapy altered tumor-immune signaling and the microenvironment.
Conclusions:
- Genomic alterations, including C10orf71 mutations and MYC/MDM2 amplifications, serve as potential biomarkers for predicting neoadjuvant chemotherapy response in gastric cancer.
- Understanding these genetic drivers and treatment-induced microenvironmental changes is key for developing personalized neoadjuvant treatment strategies.
