Identification of 4-lncRNA prognostic signature in head and neck squamous cell carcinoma

J Cell Biochem. 2019 Jun;120(6):10010-10020. doi: 10.1002/jcb.28284. Epub 2018 Dec 11.

Abstract

Deregulated long noncoding RNAs (lncRNA) have been critically implicated in tumorigenesis and serve as novel diagnostic and prognostic biomarkers. Here we sought to develop a prognostic lncRNA signature in patients with head and neck squamous cell carcinoma (HNSCC). Original RNA-seq data of 499 HNSCC samples were retrieved from The Cancer Genome Atlas database, which was randomly divided into training and testing set. Univariate Cox regression survival analysis, robust likelihood-based survival model and random sampling iterations were applied to identify prognostic lncRNA candidates in the training cohort. A prognostic risk score was developed based on the Cox coefficient of four individual lncRNA imputed as follows: (0.14546 × expression level of RP11-366H4.1) + (0.27106 × expression level of LINC01123) + (0.54316 × expression level of RP11-110I1.14) + (-0.48794 × expression level of CTD-2506J14.1). Kaplan-Meier analysis revealed that patients with high-risk score had significantly reduced overall survival as compared with those with low-risk score when patients in training, testing, and validation cohorts were stratified into high- or low-risk subgroups. Multivariate survival analysis further revealed that this 4-lncRNA signature was a novel and important prognostic factor independent of multiple clinicopathological parameters. Importantly, ROC analyses indicated that predictive accuracy and sensitivity of this 4-lncRNA signature outperformed those previously well-established prognostic factors. Noticeably, prognostic score based on quantification of these 4-lncRNA via qRT-PCR in another independent HNSCC cohort robustly stratified patients into subgroups with high or low survival. Taken together, we developed a robust 4-lncRNA prognostic signature for HNSCC that might provide a novel powerful prognostic biomarker for precision oncology.

Keywords: The Cancer Genome Atlas (TCGA); head neck squamous cell carcinoma (HNSCC); long noncoding RNA (lncRNA); prognostic biomarker; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / mortality
  • Databases, Nucleic Acid*
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / mortality
  • Humans
  • RNA, Long Noncoding* / biosynthesis
  • RNA, Long Noncoding* / genetics
  • RNA, Neoplasm* / biosynthesis
  • RNA, Neoplasm* / genetics
  • Survival Rate

Substances

  • RNA, Long Noncoding
  • RNA, Neoplasm