A telomerase regulation-related lncRNA signature predicts prognosis and immunotherapy response for gastric cancer

J Cancer Res Clin Oncol. 2023 Jan;149(1):135-146. doi: 10.1007/s00432-022-04456-6. Epub 2022 Nov 5.

Abstract

Background: Telomeres are involved in the development and progression of gastric cancer (GC). However, the association of telomerase regulation-related lncRNAs with prognosis and immunotherapy responsiveness in gastric cancer is unclear.

Methods: This study systematically evaluated the relationship between lncRNAs co-expressed with 67 telomerase regulatory genes and gastric cancer prognosis. The risk scores of the samples were calculated based on telomerase regulation-related lncRNAs with prognostic value, and the samples were classified into high-/low-risk groups. The prognostic value of risk groups was then evaluated, a GC prognostic prediction model based on risk groups and clinical characteristics was established, and the prediction accuracy of the model was clarified by receiving operating characteristic (ROC) curves and calibration curves. Finally, the value of risk grouping in GC immunotherapy sensitivity was predicted by comparing MSI status and tumor mutation load between the high- and low-risk groups.

Results: We identified 13 lncRNAs with prognostic value co-expressed with telomerase regulatory genes and observed that the prognosis of the low-risk group was significantly better than that of the high-risk group. Meanwhile, a GC overall survival (OS) prediction model based on risk grouping and clinical characteristics was developed, and ROC curves and calibration curves confirmed the good predictive ability of the model. In addition, the low-risk group exhibited a higher tumor mutation load and MSI-H, suggesting a possible benefit of immunotherapy.

Conclusion: We found that telomerase regulation-related lncRNAs have prognostic value in GC patients and contribute to the exploration of more effective immunotherapeutic strategies.

Keywords: Gastric cancer; Immunotherapy; Long non-coding RNA; Prognosis; Telomerase.

MeSH terms

  • Humans
  • Immunotherapy
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / therapy
  • Telomerase* / genetics

Substances

  • RNA, Long Noncoding
  • Telomerase