RBBP4 Enhances Platinum Chemo Resistance in Lung Adenocarcinoma

Biomed Res Int. 2021 Jan 9:2021:6905985. doi: 10.1155/2021/6905985. eCollection 2021.

Abstract

Background: The majority of lung cancers are adenocarcinomas, with the proportion being 40%. The patients are mostly diagnosed in the middle and late stages with metastasis and easy recurrence, which poses great challenge to the treatment and prognosis. Platinum-based chemotherapy is a primary treatment for adenocarcinoma, which frequently causes drug resistance. As a result, it is important to uncover the mechanisms of the chemoresponse of adenocarcinoma to platinum-based chemotherapy.

Methods: The genes from the dataset GSE7880 were gathered into gene modules with the assistance of weighted gene coexpression network analysis (WGCNA), the gene trait significance absolute value (|GS|), and gene module memberships (MM). The genes from hub gene modules were calculated with a protein-protein interaction (PPI) network analysis in order to obtain a screening map of hub genes. The hub genes with both a high |GS| and MM and a high degree were selected. Furthermore, genes in the hub gene modules also went through a Gene Ontology (GO) functional enrichment analysis.

Results: 11 hub genes in four hub gene modules (LY86, ACTR2, CDK2, CKAP4, KPNB1, RBBP4, SMAD4, MYL6, RPS27, TSPAN2, and VAMP2) were chosen as the significant hub genes. Through the GO function enrichment analysis, it was indicated that four modules were abundant in immune system functions (floralwhite), amino acid biosynthetic process (lightpink4), cell chemotaxis (navajowhite2), and targeting protein (paleturquoise). Four hub genes with the highest |GS| were verified by prognostic analysis.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / mortality
  • Antineoplastic Agents / pharmacology
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / mortality
  • Platinum Compounds / pharmacology*
  • Prognosis
  • Protein Interaction Maps / drug effects
  • Protein Interaction Maps / genetics
  • Retinoblastoma-Binding Protein 4* / genetics
  • Retinoblastoma-Binding Protein 4* / metabolism
  • Transcriptome / drug effects
  • Transcriptome / genetics

Substances

  • Antineoplastic Agents
  • Platinum Compounds
  • RBBP4 protein, human
  • Retinoblastoma-Binding Protein 4