北肿团队:哪种胃癌适合新辅助化疗?
创作:Lexi 审核:Lexi 03月02日
  • 对35例胃癌(GC)患者的84个临床样本(包括治疗前后匹配肿瘤样本)进行全基因组、全外显子组和RNA测序;
  • 对新辅助化疗非反应性的肿瘤,其微卫星不稳定性和突变负担增加;
  • 通过比较反应/非反应性肿瘤、治疗前/后样本,发现C10orf71基因突变与耐药有关,并得到药物反应数据的证实,或通过抑制细胞周期实现;
  • MYC扩增与新辅助治疗敏感性正相关,MDM2扩增与之相反;
  • 新辅助化疗重塑GC细胞免疫信号,并改变其免疫微环境。
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Lexi
虽然新辅助化疗的益处已被证实,但由于缺乏患者选择的生物标志物和对耐药机制的了解,其在胃癌治疗中的应用还很不足。来自北京大学肿瘤医院季加孚和The University of Texas MD Anderson Cancer Center的Han Liang研究团队最新发表在Science advances的研究,通过分析胃癌患者临床样本发现,对新辅助化疗非反应性的肿瘤,其微卫星不稳定性和突变负担增加。对新辅助化疗是否敏感或与C10orf71基因突变、MYC和MDM2扩增相关。该研究为开发精确的新辅助治疗方案提供了重要基础。
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Science advances [IF:13.116]

Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy

胃癌分子特征的多组学特性与新辅助化疗的反应相关

10.1126/sciadv.aay4211

02-26, Article

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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.

First Authors:
Ziyu Li,Xiangyu Gao,Xinxin Peng,Mei-Ju May Chen,Zhe Li

Correspondence Authors:
Han Liang,Jiafu Ji

All Authors:
Ziyu Li,Xiangyu Gao,Xinxin Peng,Mei-Ju May Chen,Zhe Li,Bin Wei,Xianzi Wen,Baoye Wei,Yu Dong,Zhaode Bu,Aiwen Wu,Qi Wu,Lei Tang,Zhongwu Li,Yiqiang Liu,Li Zhang,Li Zhang,Lianhai Zhang,Fei Shan,Ji Zhang,Xiaojiang Wu,Xin Ji,Ke Ji,Xiaolong Wu,Jinyao Shi,Xiaofang Xing,Jianmin Wu,Guoqing Lv,Lin Shen,Xuwo Ji,Han Liang,Jiafu Ji

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