Veneris Jennifer Taylor, Huang Lei, Churpek Jane E, Conzen Suzanne D, Fleming Gini F
Department of Medicine, Section of Hematology-Oncology, The University of Chicago, Chicago, Illinois, USA
Center for Research Informatics, The University of Chicago, Chicago, Illinois, USA.
Int J Gynecol Cancer. 2019 Feb;29(2):357-364. doi: 10.1136/ijgc-2018-000101. Epub 2019 Jan 25.
High glucocorticoid receptor (GR) protein expression is associated with decreased progression-free survival in ovarian cancer patients and decreased sensitivity to chemotherapy in preclinical models. Prior studies suggest wild type promotes GR activation. The objective of this study was to characterize the relationship of tumor GR gene expression to outcome in ovarian cancer, and to evaluate the relationship of GR expression with BRCA status.
Whole exome and whole genome sequencing, gene expression, and clinical data were obtained for high-grade serous ovarian cancers in The Cancer Genome Atlas. Cases with pathogenic somatic or germline or mutations were identified and classified as BRCA mutated. High or low glucocorticoid receptor expression was defined as expression above or below median of the / C1 () gene level. Overall survival was estimated by the Kaplan-Meier method and compared by Cox regression analysis.
Combined germline DNA sequencing and tumor microarray expression data were available for 222 high-grade serous ovarian cancer cases. Among these, 47 had a deleterious germline and/or somatic mutation in or . In multivariate analysis, high glucocorticoid receptor gene expression was associated with decreased overall survival among ovarian cancer patients, independently of BRCA mutation status. No correlation of gene expression with BRCA mutation status or or mRNA level was observed.
Increased GR gene expression is associated with decreased overall survival in ovarian cancer patients, independently of BRCA mutation status. High-grade serous ovarian cancers with high GR expression and wild type BRCA have a particularly poor outcome.
高糖皮质激素受体（GR）蛋白表达与卵巢癌患者无进展生存期缩短及临床前模型中化疗敏感性降低相关。既往研究表明野生型促进GR激活。本研究的目的是明确肿瘤GR基因表达与卵巢癌预后的关系，并评估GR表达与BRCA状态的关系。
获取癌症基因组图谱中高级别浆液性卵巢癌的全外显子组和全基因组测序、基因表达及临床数据。鉴定出具有致病性体细胞或种系或突变的病例，并分类为BRCA突变型。高或低糖皮质激素受体表达定义为高于或低于/C1（）基因水平中位数的表达。采用Kaplan-Meier法估计总生存期，并通过Cox回归分析进行比较。
共有222例高级别浆液性卵巢癌病例可获得种系DNA测序和肿瘤微阵列表达数据。其中，47例在或中有有害的种系和/或体细胞突变。在多变量分析中，高糖皮质激素受体基因表达与卵巢癌患者总生存期缩短相关，与BRCA突变状态无关。未观察到基因表达与BRCA突变状态或或mRNA水平的相关性。
GR基因表达增加与卵巢癌患者总生存期缩短相关，与BRCA突变状态无关。GR高表达且BRCA野生型的高级别浆液性卵巢癌预后尤其差。
