THSD7B Mutation Induces Platinum Resistance in Small Cell Lung Cancer Patients

Drug Des Devel Ther. 2022 Jun 3:16:1679-1695. doi: 10.2147/DDDT.S363665. eCollection 2022.

Abstract

Aim: Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort.

Patients and methods: We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis.

Results: The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance.

Conclusion: THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.

Keywords: chemotherapy resistance; gene mutation; platinum; prognosis; small cell lung cancer.

MeSH terms

  • Cisplatin / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • Platinum / pharmacology
  • Platinum / therapeutic use
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / genetics

Substances

  • Platinum
  • Cisplatin

Grants and funding

This work was supported by the Natural Science Foundation of Guangdong Province (Grant No. 2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (Grant No. 2019A030317020), Guangdong Undergraduate Training Program on Innovation and Entrepreneurship (Grant No. S202212121072) and the National Natural Science Foundation of China (Grant No. 81802257, 81871859, 81772457, 82172750 and 82172811).