Estrogen-related receptor alpha copy number variation is associated with ovarian cancer histological grade.

AIM: Copy number variations (CNVs) are related to the genetic and phenotypic diversity of cancers and identifying genetic alterations could improve treatment strategies. Here, we used The Cancer Genome Atlas (TCGA) to explore associations between estrogen-related receptor alpha (ESRRA) CNVs and histological grade in patients with ovarian cancer (OC). METHODS: Gene expression data and clinical information of 620 OC patients were obtained from The Cancer Genome Atlas）TCGA and associations between ESRRA CNVs and clinical characteristics were evaluated. Multivariate logistic regression analyses to obtain odds ratios (ORs) using a 95% confidence interval (CI) were performed, adjusting for race, age, histological grade, and tumor size. RESULTS: ESRRA CNVs were associated with histological grade (OR 0.6235 [95% CI, 0.3593-0.8877]; p < 0.05) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) CNVs (OR -0.6298 [95% CI, -0.9011 to -0.3585]; p < 0.05). In multivariate analyses, ESRRA CNVs remained significantly associated with histological grade (OR 0.6492 [95% CI, 0.3549-0.9435]; p < 0.05) and PPARGC1A CNVs (OR -0.6236 [95% CI, -0.9269 to 0.3203]; p < 0.05). CONCLUSION: There was a significant association between ESRRA CNVs in patients with OC and histological grade of the cancer.

Immunohistochemical Analysis of PGC-1α and ERRα Expression Reveals Their Clinical Significance in Human Ovarian Cancer.

PURPOSE: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and estrogen-related receptor alpha (ERRα) play a vital role in various human cancers. The purpose of this study was to investigate whether the PGC-1α/ERRα axis could serve as an effective prognostic marker in ovarian cancer (OC). PATIENTS AND METHODS: We investigated the expression of both PGC-1α and ERRα in 42 ovarian cancer and 31 noncancerous ovarian samples by immunohistochemistry (IHC). The relationship between the expression of PGC-1α and ERRα in OC and the clinical characteristics of patients was evaluated. In addition, data from the Human Protein Atlas (HPA) database were collected to validate the prognostic significance of PGC-1α and ERRα mRNA expression in OC. RESULTS: PGC-1α and ERRα showed notably higher expression in OC tissues than in noncancerous tissues (P=0.0059, P=0.002). Moreover, in patients with OC, high ERRα and PGC-1α/ERRα expression significantly correlated with tumor differentiation (P=0.027; P=0.04), lymph node status (P=0.023; P=0.021), CA125 (P=0.036; P=0.021), and HE4 (P=0.021; P=0.05), while high PGC-1α expression was only significantly associated with tumor differentiation (P=0.029). The combined analysis of high PGC-1α and ERRα expression revealed a tendency towards poor cancer-specific survival (P=0.1276). CONCLUSION: PGC-1α and ERRα are overexpressed in OC and might be significant prognostic factors for this cancer.