Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer

Abstract

Ovarian cancer is the leading cause of death among malignancies of the female reproductive system. The 5-year survival rates of ovarian cancer (OC) patients are very poor as a result of recurrent disease and emergence of drug resistance; thus, studies to find predictive markers and factors for drug resistance are ongoing. In the present study, based on the microarrays from The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) profiles covering 1648 OC patients, 11 out of 136 genes that were found to be significantly dysregulated in OC were associated with overall survival (OS) in 489 OC patients of the TCGA cohort. Of these genes, CRISP3, LYVE1, OVGP1 and BCHE were identified as independent prognostic factors, with decreased expression of the first three genes predicting shorter OS, and decreased BCHE predicting longer OS. OVGP1, BCHE and further two genes, CKAP2 and CLDN10, were consistently and remarkably associated with OS when the number of patients increased from 489 to 1583, with increased CKAP2 and decreased CLDN10 predicted shorter OS; combining the four genes provided better predictions. Associations among the four genes with OS in subgroups of OC were further verified. Downregulation of OVGP1 was significantly associated with shorter OS in all subgroups of OC patients, including subgroups of 752 patients treated with chemotherapy regimens containing taxol, 763 with both platin and taxol, 1364 with platin, 371 patients with grade 1-2 disease, 968 with grade 3 disease, 1148 with stage III-IV disease, and 439 with TP53 mutations. In addition, CKAP2 expression was significantly associated with shorter OS in 515 OC patients who had low CA125 levels. Furthermore, comprehensive analyses that including RT-qPCR, bioinformatics analysis and clinical data revealed an association of CKAP2, BCHE, CLDN10 and OVGP1 with drug resistance in OC. The genes identified in the present study might be prognostic factors as well as potential therapeutic targets in the treatment of OC.

Development and validation of hub genes for lymph node metastasis in patients with prostate cancer

“…A recent study revealed that high expression of CKAP2L promoted the invasion of lung cancer through MAPK signalling pathway and was associated with poor prognosis . In addition, the oncogenic nature of CKAP2, which is an important paralog of CKAP2L, has also been illustrated in ovarian cancer, glioma and breast cancer . CKAP2L is a promising candidate gene that may affect the tumorigenesis and lymph node metastasis of PCa; however, more studies are required to confirm it.…”

Microarray‐based identification of genes associated with prognosis and drug resistance in ovarian cancer

“…24 The use of those large datasets may reveal genes that should be investigated more closely and that may eventually lead to new drug treatments and discovery of new biomarkers. Similarly, using the data of Oncomine, TCGA, and GEO profiles, we identified four genes that are significantly associated with drug resistance and prognosis in OC, 16 six that are associated with OC progression, 11,12 and 11 that are associated with tumor progression and prognosis in hepatocellular carcinoma. They found that the high expression of ABCA1, ABCA6, ABCA8, and ABCA9, and the low expression of ABCA5 was associated with shorter survival in patients with OC; and the combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with a particularly poor outcome.…”

“…They found that the high expression of ABCA1, ABCA6, ABCA8, and ABCA9, and the low expression of ABCA5 was associated with shorter survival in patients with OC; and the combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with a particularly poor outcome. Similarly, using the data of Oncomine, TCGA, and GEO profiles, we identified four genes that are significantly associated with drug resistance and prognosis in OC, 16 six that are associated with OC progression, 11,12 and 11 that are associated with tumor progression and prognosis in hepatocellular carcinoma. 26 Therefore, the large data set from the TCGA cohort and the GEO profiles were used to identify genes associated with both drug resistance and prognosis in OC.…”

“…6 Various factors contribute to drug resistance and can predict prognosis in OC, including microRNAs, long noncoding RNAs, epigenetic changes, and so on. 10 We previously reviewed 25 oncogenes 11,12 and 15 tumor suppressor genes, 13 and identified several genes (such as NEK11 and TRPC1) 11,12,[14][15][16] that are associated with drug resistance or/ and prognosis in OC. For example, at least 30 genes that affect the regulation of DNA repair/damage, cell cycle, and apoptosis are associated with drug resistance or prognosis in OC.…”

Dexmedetomidine mediates microRNA-185 to suppress ovarian cancer growth via inhibiting the SOX9/Wnt/β-catenin signaling pathway

“…Despite the efficient surgical debulking and the application of different anticancer drug combinations, the overall 5-year survival rate of advanced OC patients was less than 40% with only modest improvement over decades (Gao and Liu, 2017;Varughese and Cocco, 2011). Investigating biomarkers enabling early diagnosis of OC and developing novel therapies continue to be fundamental goals for researchers in the field of OC.…”