Prognostic model of lung adenocarcinoma constructed by the CENPA complex genes is closely related to immune infiltration

Pathol Res Pract. 2021 Dec:228:153680. doi: 10.1016/j.prp.2021.153680. Epub 2021 Nov 3.

Abstract

Background: Lung adenocarcinoma (LUAD) is still one of the primary malignant diseases leading to higher mortality worldwide. It has been previously reported that multiple genes in the CENPA-nucleosome associated complex (NAC) complex in lung cancer can be used as prognostic markers; however, there is lack of comprehensive research on the CENPA-NAC complex.

Methods: The hub genes of lung cancer were obtained by analyzing multiple gene expression omnibus (GEO) lung cancer datasets. The key genes of the CENPA-NAC complex in the evolution of LUAD were identified according to lung cancer data obtained from The Cancer Genome Atlas (TCGA) database, and the key genes were constructed as a survival prognostic model. The relationship between the model and immune cell infiltration was studied by the Tumor Immune Estimation Resource (TIMER) and single-sample gene set enrichment analysis (ssGSEA) studies.Droplet Digital polymerase chain reaction (ddPCR) was used to verify the effectiveness of the prognostic model to predict survival using clinical samples.

Results: A comprehensive study showed that CENPA, CENPH, CENPM, CENPN and CENPU were key genes in the development and evolution of LUAD. The constructed survival prognosis model was an independent risk factor for LUAD and can be used to assess the survival of LUAD patients. The risk score was closely related to the infiltration of multiple immune cells. The independent cohorts GSE31210 and GSE50081 further confirmed the validity of the prognostic model, and finally, the model was validated with clinical samples.

Conclusions: In conclusion, the results of the present study showed that CENPA, CENPH, CENPM, CENPN, and CENPU are a group of potential prognostic markers in LUAD. The constructed model has been confirmed to be applicable in the clinical setting in evaluating the survival of patients with LUAD, and providing more evidence on immunotherapy for LUAD.

Keywords: CENPA-NAC complex; CENPA/H/M/N/U; DdPCR; Immune infiltration; Lung adenocarcinoma; Prognostic model.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology*
  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor*
  • Centromere Protein A / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Gene Regulatory Networks
  • Histones / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology*
  • Male
  • Middle Aged
  • Nucleosomes
  • Prognosis
  • Rabbits
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Nucleosomes