RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with radiotherapy response of nasopharyngeal carcinoma and prognosis of head and neck cancer

Cancer Biol Ther. 2020;21(2):139-146. doi: 10.1080/15384047.2019.1670521. Epub 2019 Nov 7.

Abstract

Radiotherapy is the main treatment for nasopharyngeal carcinoma (NPC); however, radioresistance limits the therapeutic efficacy and prognosis of patients with NPC. Here, we plan to identify the genes involved in radiotherapy response. Peripheral blood mononuclear cells (PBMC) from three paired NPC patients with pre-radiotherapy and post-radiotherapy were extracted. Next-generation deep sequencing was then performed to identify the PBMCs transcripts profiles in response to radiotherapy. Data of gene chip GSE48501 was obtained from Gene Expression Omnibus (GEO) database. The gene integration of differentially expressed genes identified from RNA-Seq data and gene chip was performed using "RobustRankAggreg" package. RNA-Seq data from 44 normal and 519 Head and neck squamous cell carcinoma (HNSCC) tissues (downloaded from TCGA) was integrated into the analysis to further support our study. Cox regression was used to identify risk factors impacting survival. Total of 45 genes were identified to be associated with radiotherapy response. Significantly enriched Gene Ontology (GO) terms and pathways were enriched. Univariate and multivariate analysis suggested the dysregulated genes, CHAC2, CLEC9A, GNG10, JCHAIN, KLRB1, NOG, OLR1, PRELID2, SYT1, VWCE, ZNF443 were associated with survival in HNSCC patients. Our data provide an overview of the profiles of radiotherapy-associated genes, which will facilitate future investigations into the function of radiotherapy resistance.

Keywords: Biomarker; Circulating cell; Head and neck cancer; Nasopharyngeal carcinoma; RNA-Seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Case-Control Studies
  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / radiation effects
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy
  • Prognosis
  • RNA-Seq / methods
  • Radiation Tolerance / genetics*
  • Radiotherapy / methods
  • Survival Rate
  • Transcriptome / radiation effects*

Substances

  • Biomarkers, Tumor

Grants and funding

This work was supported by the National Natural Science Foundation of China (81872200, 31900558), the Natural Science Foundation of Hubei Province (2018CFB510), the Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (ZNPY2018090, ZNPY2017029), and the Fundamental Research Funds for the Central Universities (2042019kf0139, 2042018kf0091).