High Expression Levels of AGGF1 and MFAP4 Predict Primary Platinum-Based Chemoresistance and are Associated with Adverse Prognosis in Patients with Serous Ovarian Cancer

Primary platinum-based chemoresistance occurs in approximately one-third of patients with serous ovarian cancer (SOC); however, traditional clinical indicators are poor predictors of chemoresistance. So we aimed to identify novel genes as predictors of primary platinum-based chemoresistance. Gene expression microarray analyses were performed to identify the genes related to primary platinum resistance in SOC on two discovery datasets (GSE51373, GSE63885) and one validation dataset (TCGA). Univariate and multivariate analyses with logistic regression were performed to evaluate the predictive values of the genes for platinum resistance. Machine learning algorithms (linear kernel support vector machine and artificial neural network) were applied to build prediction models. Univariate and multivariate analyses with Cox proportional hazards regression and log-rank tests were used to assess the effects of these gene signatures for platinum resistance on prognosis in two independent datasets (GSE9891, GSE32062). AGGF1 and MFAP4 were found highly expressed in patients with platinum-resistant SOC and independently predicted platinum resistance. Platinum resistance prediction models based on these targets had robust predictive power (highest AUC: 0.8056, 95% CI: 0.6338-0.9773; lowest AUC: 0.7245, 95% CI: 0.6052-0.8438). An AGGF1- and MFAP4-centered protein interaction network was built, and hypothetical regulatory pathways were identified. Enrichment analysis indicated that aberrations...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research