Abstract 4692: ARL4C, a novel ovarian cancer-related gene, its down-regulated predicts poor survival in ovarian cancer.

Abstract

Abstract Purpose: To identify the genes involved in ovarian cancer progression and elucidate their biological actions in ovarian cancer. Experimental Design: Comparative genomic hybridization (CGH) was employed to screen the chromosome fragments with different copy numbers between the ovarian cancer cell line HO-8910 and its highly metastatic cell subline HO-8910PM. Fluorescent in situ hybridization (FISH) via biotin-labeled BAC clone probes was used to validate the results of CGH. Using gene expression microarray, differentially expressed genes on the target chromosome fragment were compared between the two cell lines. Lentiviral-mediated transfection was used to investigate the effects of candidate gene over-expression or knockdown on colony formation, proliferation and motility of ovarian cancer cells. Two hundred twelve epithelial ovarian cancer samples were analyzed for mRNA expression of candidate gene using RT-PCR. Associations of the gene expression with clinicopathological factors, progression free and overall survival were evaluated. Results: Chromosome fragment 2q36.1-37.3 was found hemizygous deletion in HO-8910PM cells by CGH and FISH. Comparing gene expression data, we identified ARL4C, located on chromosome 2q37.1, to be down-regulated in the HO-8910PM cells, compared with the HO-8910 cells. Western blot showed ARL4C expression was low/null in most ovarian cancer cell lines, including the HO-8910PM cells. ARL4C over-expression or knockdown had no obvious effect on colony formation and cell proliferation, but negatively regulated cell motility. ARL4C over-expression suppressed ovarian cancer cells migration and invasion. Inversely, ARL4C knockdown promoted ovarian cancer cells migration. Clinicopathologic studies further supported the relevance of ARL4C in ovarian cancers. Patients with medium or high levels of ARL4C mRNA were at lower risk for death, compared to those with low levels (HR, 0.45; 95% C.I., 0.27-0.76; P=0.003 for mid levels; and HR, 0.58; 95% C.I., 0.35-0.96; P = 0.035 for high levels) after adjusting for age, disease stage, tumor grade, histologic type and residual tumor size. Kaplan-Meier survival analysis demonstrated similar results. Conclusions: ARL4C is a novel ovarian cancer related gene that inhibits cell motility. It seems to play a protective role in cancer progression and is an independent prognostic factor for patient with ovarian cancer. More studies are needed to further elucidate the molecular mechanisms of ARL4C in ovarian cancer progression. Citation Format: Dan Su, Shenhau Xu, Haiyan Xu, Yun Gao, Jianguo Feng, Min Luo, Lisha Ying, Nengming Lin, Dionyssios Katsaros, Herbert Yu. ARL4C, a novel ovarian cancer-related gene, its down-regulated predicts poor survival in ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4692. doi:10.1158/1538-7445.AM2013-4692