A innovative prognostic symbol based on neutrophil extracellular traps (NETs)-related lncRNA signature in non-small-cell lung cancer

Aging (Albany NY). 2021 Jul 13;13(13):17864-17879. doi: 10.18632/aging.203289. Epub 2021 Jul 13.

Abstract

Neutrophil extracellular traps (NETs) are closely related to cancer progression. NETs-related lncRNAs play crucial roles in non-small-cell lung cancer (NSCLC) but there have been no systematic studies regarding NETs-related long noncoding RNA (lncRNA) signatures to forecast the prognosis of NSCLC patients. It's essential to build commensurate NETs-related lncRNA signatures. The expression profiles of prognostic mRNAs and lncRNAs and relevant clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The NETs-related genes came from the results of our transcriptome RNA microarray data. The co-expression network of lncRNAs and NETs-related genes was structured to confirm NETs-related lncRNAs. The 19 lncRNAs correlated with overall survival (OS) were selected by exploiting univariate Cox regression (P < 0.05). Lasso regression and multivariate Cox regression (P < 0.05) were utilized to develop a 12-NETs-related lncRNA signature. We established a risk score based on the signature, which suggested that patients in the high-risk group displayed significantly shorter OS than patients in the low-risk group (P < 0.0001, P = 0.0023 respectively in the two cohorts). The risk score worked as an independent predictive factor for OS in both univariate and multivariate Cox regression analyses (HR> 1, P< 0.001). Additionally, by RT-qPCR, we confirmed that NSCLC cell lines have higher levels of the three adverse prognostic NETs-related lncRNAs than normal lung cells. The expression of lncRNAs significantly increases after NETs stimulation. In short, the 12 NETs-related lncRNAs and their model could play effective roles as molecular markers in predicting survival for NSCLC patients.

Keywords: lncRNA; neutrophil extracellular traps; non-small-cell lung cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Computational Biology
  • Extracellular Space / chemistry*
  • Extracellular Traps / chemistry*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Neutrophils / chemistry*
  • Predictive Value of Tests
  • Prognosis*
  • RNA, Long Noncoding / analysis*
  • Risk Assessment
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding