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

Lung Cancer. 2023 Jul:181:107255. doi: 10.1016/j.lungcan.2023.107255. Epub 2023 May 20.

Abstract

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 frequency 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.

Keywords: EGFR; Genetic characteristics; Lung cancer; Microsatellite Instability-High (MSI-H); Microsatellite Stability (MSS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / metabolism
  • Cohort Studies
  • Colorectal Neoplasms* / pathology
  • Genomics
  • Humans
  • Lung Neoplasms*
  • Microsatellite Instability
  • Mutation
  • Prognosis
  • Receptor, Transforming Growth Factor-beta Type II / genetics

Substances

  • B7-H1 Antigen
  • Receptor, Transforming Growth Factor-beta Type II