Elevated AKIP1 expression is associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma

Abstract

A-kinase-interacting protein 1 (AKIP1), as a recently discovered oncoprotein, promotes cell malignant behaviors in gynecological malignancies. To the best of our knowledge, no study reports its clinical value in patients with endometrial carcinoma. The present study aimed to explore the association between AKIP1 expression and clinical features and survival in patients with endometrial carcinoma, and to assess the effect of AKIP1 knockdown on the regulation of chemosensitivity in vitro. The tumor and adjacent tissue specimens from 101 patients with endometrial carcinoma were retrieved for AKIP1 protein expression analysis using an immunohistochemistry (IHC) assay. Meanwhile, specimens from 54 patients with endometrial carcinoma were analyzed for AKIP1 mRNA expression using reverse transcription-quantitative PCR. Furthermore, an in vitro experiment was conducted in the Ishikawa cell line to determine the effect of AKIP1 modification on the chemosensitivity of cisplatin and paclitaxel. AKIP1 IHC score (P<0.001) and mRNA expression levels (P<0.001) were increased in tumor tissues compared with those in adjacent tissues. Moreover, increased AKIP1 IHC score was associated with lymphovascular invasion (P=0.007), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.002) and shorter overall survival (OS) time (P=0.035) in the patients with endometrial carcinoma. Meanwhile, upregulated AKIP1 mRNA expression levels were associated with lymphovascular invasion (P=0.020) and advanced FIGO stage (P=0.027) in the patients with endometrial carcinoma. Multivariate Cox regression showed that tumor AKIP1 protein expression (high vs. low) independently predicted a shorter OS time (P=0.036). Silencing of AKIP1 decreased Ishikawa cell viability when treated with 5, 10, 20 and 40 µM cisplatin (all P<0.05) and decreased the half maximal inhibitory concentration value of cisplatin (P=0.003), whereas its effect on paclitaxel chemosensitivity was less obvious. Overall, elevated AKIP1 expression was associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma.