Involvement of miR-29b signaling in the sensitivity to chemotherapy in patients with ovarian carcinoma

• Published in: Human pathology 2014-06, Vol.45 (6), p.1285-1293
• Main Authors: Dai, Furong, Zhang, Yi, Chen, Yuxiang, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - mortality; ATG9A; Autophagy; Autophagy-Related Proteins; Cancer therapies; Chemotherapy; Confidence intervals; Disease-Free Survival; Drug Resistance, Neoplasm - genetics; Female; Gene expression; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Kinases; MAPK10; Mcl1; Medical prognosis; Membrane Proteins - genetics; Metastasis; MicroRNAs - genetics; miR-29b; Mitogen-Activated Protein Kinase 10 - genetics; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Overall survival; Pathology; Progression-free survival; Proportional Hazards Models; Proteins; Real-Time Polymerase Chain Reaction; Signal Transduction; Vesicular Transport Proteins
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2014.02.008

Summary Although the molecular mechanisms driving chemoresistance and relapse of ovarian cancer have been widely studied, the key molecules have not been identified. In this study, the expression of miR-29b messenger RNA (mRNA) and its targeted genes, myeloid cell leukemia sequence 1 , mitogen-activated protein kinase 10 ( MAPK10 ), and autophagy-related protein 9A ( ATG9A ), were investigated in ovarian carcinomas, and their associations with clinicopathological characteristics and survival of patients with ovarian cancer were analyzed. The protein expression of MCL1, MAPK10, and ATG9A was measured using immunohistochemistry. miR-29b mRNA and ATG9A gene mRNA levels were measured by real-time polymerase chain reaction. Results demonstrated that the percentage of MCL1, MAPK10, and ATG9A protein–positive cases were significantly higher, whereas miR-29b was significantly lower in ovarian serous, mucinous, and clear cell carcinomas than that in normal tissues. MAPK10 was significantly associated with higher histopathologic grading. The percentage of positive myeloid cell leukemia sequence 1, ATG9A, and MAPK10 protein expression and low miR-29b mRNA expression were significantly higher in cases with clinical stage III and IV ovarian cancer than in cases with clinical stage II ovarian cancer. High ATG9A protein and low miR-29b mRNA expression were significantly associated with relapse. Univariate Kaplan-Meier analysis showed a negative correlation between MAPK10 or ATG9A protein expression and overall as well as progression-free survival, whereas a positive correlation was observed between miR-29b mRNA expression and overall as well as progression-free survival. Multivariate Cox regression analysis showed that elevated MAPK10 or ATG9A protein and lowered miR-29b mRNA expression in ovarian carcinoma was an independent poor prognostic predictor. Our study suggested that miR-29b mRNA, MAPK10 protein expression, and ATG9A protein expression are closely related to chemosensitivity of ovarian carcinoma.