Microarray‐based identification of genes associated with prognosis and drug resistance in ovarian cancer. Issue 4 (18th October 2018)

• Record Type: Journal Article
• Authors: Yin, Fuqiang; Yi, Shang; Wei, Luwei; Zhao, Bingbing; Li, Jinqian; Cai, Xiangxue; Dong, Caihua; Liu, Xia
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 4(2019)
• Page Start: 6057
• Page End: 6070
• Publication Date: 2018-10-18
• Subjects: disease‐free survival (DFS) -- drug resistance -- ovarian cancer (OC) -- overall survival (OS) -- PDIA4 -- prognosis; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27892
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: The outcome for patients with ovarian cancer (OC) is poor because of drug resistance. Therefore, identification of factors that affect drug resistance and prognosis in OC is needed. In the present study, we identified 131 genes significantly dysregulated in 90 platinum‐resistant OC tissues compared with 197 sensitive tissues, of which 30 were significantly associated with disease‐free survival (DFS; n = 16), overall survival (OS; n = 6), or both (n = 8) in 489 OC patients of the The Cancer Genome Atlas cohort. Of these 30 genes, 17 were significantly upregulated and 13 were downregulated in the 90 resistant tissues, and with one exception, all of the up‐/downregulated genes in resistant tissues were predictors of shorter DFS or/and OS. LAX1, MECOM, and PDIA4 were independent risk factors for DFS, and KLF1, SLC7A11, and PDIA4 for OS; combining these genes provided more accurate predictions for DFS and OS than any of the genes used individually. We further verified downregulation of PDIA4 protein in 51 specimens of patients with OC (24 drug resistant's and 27 sensitive's), which confirmed that downregulated PDIA4 predicted DFS and OS. PDIA4 also consistently predicted OS in a larger sample of 1656 patients with OC. These 30 genes, particularly the PDIA4, could be therapeutic targets or biomarkers for managing OC. Abstract : 1. Thirty genes were first identified to be significantly dysregulated in platinum‐resistant ovarian cancer (OC) tissues, and all these genes with changed expression in resistant tissues (up‐ or downregulated) predicted shorter disease‐free survival or/and overall survival. 2. PDIA4 was an independent risk factor for both disease‐free survival (DFS) and overall survival (OS), and its combination with LAX1/MECOM and KLF1/SLC7A11 provided more accurate predictions for DFS and OS than any of the genes used individually. 3. PDIA4 was consistently downregulated in drug‐resistant tissues, and low expression of the gene consistently predicted poor DFS and OS in The Cancer Genome Atlas cohort and lab‐collected 51 specimens of patients with OC, and also consistently predicted OS in a larger sample of 1656 patients with OC, which was a collection of 14 independent microarrays.