Dataset Information

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

ABSTRACT: 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 of extracellular matrix may play important roles in platinum resistance in SOC. High AGGF1 and MFAP4 expression levels were also related to shorter recurrence-free and overall survival in patients with SOC after adjustment for other clinical variables. Therefore, AGGF1 and MFAP4 are potential predictive biomarkers for response to platinum-based chemotherapy and survival outcomes in SOC.

SUBMITTER: Zhao H

PROVIDER: S-EPMC6360311 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Zhao Haiyue H Sun Qian Q Li Lisong L Zhou Jinhua J Zhang Cong C Hu Ting T Zhou Xuemei X Zhang Long L Wang Baiyu B Li Bo B Zhu Tao T Li Hong H

Journal of Cancer 20190101 2

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). Univar ...[more]

PMID: 30719133

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Project description:BackgroundPrimary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients.MethodsIn this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan-Meier.ResultsIn advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60-97.00%, 46.40-89.30% and 0.774-0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression.ConclusionsAs a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.

Dataset Information

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

Publications

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

Similar Datasets

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