Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers

Front Immunol. 2024 Jun 18:15:1338162. doi: 10.3389/fimmu.2024.1338162. eCollection 2024.

Abstract

Introduction: Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched.

Methods: In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance.

Results: Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed PRICKLE3, TNFSFI0, ACSLl and EP300 as potential contributors to primary resistance, with SNWl, SENP2 and SMNDCl emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC.

Discussion: These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.

Keywords: SCLC; acquired resistance; chemotherapy resistance; gene expression; network analysis; primary resistance.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Drug Resistance, Neoplasm* / genetics
  • Etoposide / pharmacology
  • Etoposide / therapeutic use
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / blood
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Male
  • Middle Aged
  • Small Cell Lung Carcinoma* / blood
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / genetics
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • Etoposide

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Function China fund (No. 32070683) awarded to YC.