Platinum Drug Sensitivity Polymorphisms in Stage III Non-small Cell Lung Cancer With Invasion of Mediastinal Lymph Nodes

Cancer Genomics Proteomics. 2020 Sep-Oct;17(5):587-595. doi: 10.21873/cgp.20215.

Abstract

Background/aim: Patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients.

Patients and methods: Whole-exome sequencing (WES) was performed on samples from 11 patients with no response after induction chemotherapy and 6 patients with documented pathological response, admitted to the Hotel Dieu Hospital, Paris or Allegemeines Krakenhaus University, Vienna.

Results: A higher alternative allele frequency was found on SENP5, rs63736860, rs1602 and NCBP2, rs553783 in the non-responder group, and on RGP1, rs1570248, SLFN12L, rs2304968, rs9905892, and GBA2, rs3833700 in the responder group.

Conclusion: These polymorphisms contribute to inter-individual sensibility to chemotherapy response. Interrogation of these genetic variations may have potential applicability when deciding the treatment strategy for patients with stage III NSCLC (N2).

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

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Carboplatin / pharmacology
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemotherapy, Adjuvant / methods
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Exome Sequencing
  • Female
  • Humans
  • Induction Chemotherapy / methods
  • Lung / diagnostic imaging
  • Lung / drug effects
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Lymphatic Metastasis / therapy*
  • Male
  • Mediastinum / diagnostic imaging
  • Mediastinum / pathology
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging
  • Pneumonectomy
  • Polymorphism, Single Nucleotide
  • Precision Medicine / methods
  • Prospective Studies
  • Thoracoscopy
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Carboplatin
  • Cisplatin