RORα and REV-ERBα are Associated With Clinicopathological Parameters and are Independent Biomarkers of Prognosis in Gastric Cancer

Technol Cancer Res Treat. 2021 Jan-Dec:20:15330338211039670. doi: 10.1177/15330338211039670.

Abstract

Retinoid-related orphan receptor alpha (RORα) and nuclear receptor subfamily 1 group D member 1 (REV-ERBα) play critical roles in many human cancers. Whether RORα and REV-ERBα expression levels are associated with clinical characteristics are poorly understood, and they may be independent predictors of overall survival (OS) and progression-free survival (PFS) in gastric cancer (GC). This study aimed to investigate the correlation of RORα and REV-ERBα expression levels with clinicopathological parameters, OS, and PFS in GC. Immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were employed to assess the expression levels of RORα and REV-ERBα, which were downregulated in GC tissues compared with normal gastric tissues (P < .001; P < .001) and were associated with several clinicopathological parameters, including histological grade (P = .032; P < .001), preoperative carcinoembryonic antigen (CEA) levels (P = .004; P < .001), and tumor-node-metastasis (TNM) stage (P = .015; P < .001). Additionally, low RORα and REV-ERBα expression levels were associated with poor OS and PFS in GC patients, respectively (P < .001; P = .001). Furthermore, univariate Cox regression model analysis showed that histological grade (P < .001; P < .001), preoperative CEA levels (P < .001; P = .001), TNM stage (P < .001; P < .001), lymph node metastasis (P = .002; P = .002), RORα expression levels (P = .001; P < .001), and REV-ERBα expression levels (P < .001; P = .001) were associated with OS and PFS in GC. Multivariate Cox regression model analysis indicated that RORα expression levels and REV-ERBα expression levels are independent factors of OS and PFS in GC. Besides, RORα and REV-ERBα expression may be positively correlated (χ2 = 6.835; P = .009), and GC patients with both high RORα and REV-ERBα expression levels had the best prognosis. In conclusion, RORα and REV-ERBα may coparticipate in tumor activities and show potential to estimate the prognosis of GC.

Keywords: RORα; biomarkers; gastric cancer; prognosis; rEV-ERBα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoembryonic Antigen / blood
  • Down-Regulation
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics*
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics*
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism*
  • Progression-Free Survival
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Survival Rate

Substances

  • Carcinoembryonic Antigen
  • NR1D1 protein, human
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • RORA protein, human