Molecular Markers for Long-term Survival in Stage IIIA (N2) NSCLC Patients

Cancer Genomics Proteomics. 2022 Jan-Feb;19(1):94-104. doi: 10.21873/cgp.20306.

Abstract

Background: Survival rates among non-small cell lung cancer (NSCLC) stage IIIA (N2) patients are generally low and depend on the treatment.

Patients and methods: We aimed to identify predictive markers for long term survival in responders and non-responders to chemotherapy, analyzing tumour and non-tumour samples by microarray (n=35) and whole exome sequencing (WES, n=25).

Results: WES data showed correlation of overall survival of all patients with rs9905892 in the SLFN12L gene. High frequency of mutations (4/6, 66.7%) was identified in members of SWI/SNF complex in responder patients and in patients that were alive after seven years. Microarray data for immune components showed that VISTA (VSIR) was down-regulated in tumoral tissue.

Conclusion: Our research suggests that mutations in SWI/SNF complex associate with long term survival after multimodal treatment, while down-regulation of VISTA might indicate its immunomodulatory role in NSCLC stage III (N2) patients.

Keywords: NSCLC; Whole-exome sequencing; platinum sensitivity.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • B7 Antigens / genetics
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Chemoradiotherapy
  • Chemotherapy, Adjuvant
  • Drug Resistance, Neoplasm / genetics
  • Exome Sequencing
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Pneumonectomy
  • Retrospective Studies
  • Risk Assessment / methods
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • B7 Antigens
  • Biomarkers, Tumor
  • VSIR protein, human