Retinoic acid-related orphan receptor C isoform 2 expression and its prognostic significance for non-small cell lung cancer

J Cancer Res Clin Oncol. 2016 Jan;142(1):263-72. doi: 10.1007/s00432-015-2040-0. Epub 2015 Aug 30.

Abstract

Background: Retinoic acid-related orphan receptor C isoform 2 (RORC2) is regarded as a pathogenic factor for autoimmune and inflammatory diseases and tumours. Previous studies have primarily focused on RORC2 expression in IL-17-producing immune cells but not in carcinoma cells; thus, little is known about the roles of RORC2 in the progression of human non-small cell lung cancer (NSCLC). In this study, we analysed the expression of RORC2 and its participation in tumour progression in NSCLC.

Methods: RORC2 expression in NSCLC and adjacent normal lung tissues was assessed via quantitative real-time PCR (qRT-PCR) and immunohistochemistry. RORC2 expression in NSCLC cell lines was examined by qRT-PCR, Western blotting and flow cytometry. The effects of inhibiting RORC2 activity on the proliferation of NSCLC cells were evaluated. The prognostic value of RORC2 for NSCLC was revealed based on Kaplan-Meier analysis.

Results: High RORC2 expression was observed in lung cancer tissues and was significantly related to age (p = 0.013) and regional lymph node metastasis (p = 0.009). RORC2 expression was higher in the A549, H460, SPC-A1 and H1299 cell lines than in a control cell line. In addition, cell proliferation was decreased in NSCLC cells upon the blocking of RORC2 activity using a specific inhibitor. High RORC2 expression correlated with worse overall survival (p = 0.030).

Conclusions: Our study suggests that RORC2 is expressed by lung cancer cells and greatly contributes to tumour cell proliferation and overall survival in NSCLC. These findings strongly imply that RORC2 is associated with tumour progression.

Keywords: Cell proliferation; Non-small cell lung cancer; Prognosis; RORC2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / metabolism
  • Carcinoma, Adenosquamous / mortality
  • Carcinoma, Adenosquamous / secondary
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / secondary
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
  • Prognosis
  • Protein Isoforms
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Protein Isoforms
  • RNA, Messenger
  • RORC protein, human