TY - JOUR
T1 - Identification and validation of potential prognostic and predictive miRNAs of epithelial ovarian cancer
AU - Prahm, Kira Philipsen
AU - Høgdall, Claus
AU - Karlsen, Mona Aarenstrup
AU - Christensen, Ib Jarle
AU - Novotny, Guy Wayne
AU - Høgdall, Estrid
PY - 2018/11
Y1 - 2018/11
N2 - BACKGROUND: Ovarian cancer is the leading cause of death by gynecologic cancers in the Western world. The aim of the study was to identify microRNAs (miRNAs) associated with prognosis and/or resistance to chemotherapy among patients with epithelial ovarian cancer.METHODS: Using information from the Pelvic Mass Study we identified a cohort of women with epithelial ovarian cancer. Tumor tissues were then collected and analyzed by global miRNA microarrays. MiRNA profiling was then linked to survival and time to progression using Cox proportional-hazards regression models. Logistic regression models were used for the analysis of resistance to chemotherapy. Our results were validated using external datasets retrieved from the NCBI Gene Expression Omnibus database.RESULTS: A total of 197 patients with epithelial ovarian cancer were included for miRNA microarray analysis. In multivariate analyses we identified a number of miRNAs significantly correlated with overall survival (miR-1183 (HR: 1.42, 95% CI:1.17-1.74, p = 0.0005), miR-126-3p (HR: 1.38, 95% CI:1.11-1.71, p = 0.0036), time to progression (miR-139-3p (HR: 1.48, 95% CI: 1.13-1.94, p = 0.0047), miR-802 (HR: 0.48, 95% CI: 0.29-0.78, p = 0.0035)), progression free survival (miR-23a-5p (HR:1.32, 95% CI:1.09-1.61, p = 0.004), miR-23a-3p (HR:1.70, 95% CI:1.15-2.51, p = 0.0074), miR-802 (HR: 0.48, 95% CI: 0.29-0.80, p = 0.0048)), and resistance to chemotherapy (miR-1234 (HR: 0.26, 95% CI: 0.11-0.64, p = 0.003)). A few miRNAs identified in our training cohort, were validated in external cohorts with similar results.CONCLUSION: Eight miRNAs were identified as significant predictors of overall survival, progression free survival, time to progression, and chemotherapy resistance. A number of these miRNAs were significantly validated using external datasets. Inter-platform and inter-laboratory variations may have influence on the ability to compare and reproduce miRNA results. The use of miRNAs as potential markers of relapse and survival in ovarian cancer warrants further investigation.
AB - BACKGROUND: Ovarian cancer is the leading cause of death by gynecologic cancers in the Western world. The aim of the study was to identify microRNAs (miRNAs) associated with prognosis and/or resistance to chemotherapy among patients with epithelial ovarian cancer.METHODS: Using information from the Pelvic Mass Study we identified a cohort of women with epithelial ovarian cancer. Tumor tissues were then collected and analyzed by global miRNA microarrays. MiRNA profiling was then linked to survival and time to progression using Cox proportional-hazards regression models. Logistic regression models were used for the analysis of resistance to chemotherapy. Our results were validated using external datasets retrieved from the NCBI Gene Expression Omnibus database.RESULTS: A total of 197 patients with epithelial ovarian cancer were included for miRNA microarray analysis. In multivariate analyses we identified a number of miRNAs significantly correlated with overall survival (miR-1183 (HR: 1.42, 95% CI:1.17-1.74, p = 0.0005), miR-126-3p (HR: 1.38, 95% CI:1.11-1.71, p = 0.0036), time to progression (miR-139-3p (HR: 1.48, 95% CI: 1.13-1.94, p = 0.0047), miR-802 (HR: 0.48, 95% CI: 0.29-0.78, p = 0.0035)), progression free survival (miR-23a-5p (HR:1.32, 95% CI:1.09-1.61, p = 0.004), miR-23a-3p (HR:1.70, 95% CI:1.15-2.51, p = 0.0074), miR-802 (HR: 0.48, 95% CI: 0.29-0.80, p = 0.0048)), and resistance to chemotherapy (miR-1234 (HR: 0.26, 95% CI: 0.11-0.64, p = 0.003)). A few miRNAs identified in our training cohort, were validated in external cohorts with similar results.CONCLUSION: Eight miRNAs were identified as significant predictors of overall survival, progression free survival, time to progression, and chemotherapy resistance. A number of these miRNAs were significantly validated using external datasets. Inter-platform and inter-laboratory variations may have influence on the ability to compare and reproduce miRNA results. The use of miRNAs as potential markers of relapse and survival in ovarian cancer warrants further investigation.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Ovarian Epithelial/genetics
KW - Databases, Nucleic Acid
KW - Disease-Free Survival
KW - Female
KW - Gene Expression Profiling
KW - Humans
KW - MicroRNAs/biosynthesis
KW - Middle Aged
KW - Oligonucleotide Array Sequence Analysis
KW - Ovarian Neoplasms/genetics
KW - RNA, Neoplasm/biosynthesis
KW - Survival Rate
U2 - 10.1371/journal.pone.0207319
DO - 10.1371/journal.pone.0207319
M3 - Journal article
C2 - 30475821
SN - 1932-6203
VL - 13
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 11
M1 - e0207319
ER -
