Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study

作者：Tian, Jie; Wang, Hongdan; Lu, Conghua; Liu, Lan; Zhang, Xianquan; Xie, Yunbo; Li, Rutian; Lv, Xin; Fu, Dan; Zhang, Ling; Fang, Xisheng; Wang, Xuming; Hu, Jing; Liu, Xinyi; Huang, Xiaochun; Zhao, Qian; Luo, Nuo; Tang, Huan; Zhong, Zhaoyang^*; He, Yong^*; Li, Li^*

来源：Lung Cancer, 2023, 181: 107255.

DOI：10.1016/j.lungcan.2023.107255

• Microsatellite Instability-High (MSI-H)
• Microsatellite Stability (MSS)
• Lung cancer
• Genetic characteristics
• EGFR

Background: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported.Methods: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression.Results: Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation fre-quency than in MSS.Conclusion: The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.

• 单位
  南京大学; y; 中国科学院研究生院; 1; 南昌大学