Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients.

Leticia Oliveira-Ferrer,Roshni Goswami,Karen Legler,Yi Ding,Vladimir Galatenko,Barbara Schmalfeldt,Sascha Kürti,Karin Milde-Langosch,Kathrin Eylmann

doi:10.1155/2018/6714287

Abstract

The underlying mechanisms of ovarian cancer (OvCa) dissemination are still poorly understood, and novel molecular markers for this cancer type are urgently needed. In search of adhesion molecules with prognostic relevance in OvCa, we compared tumors with good outcome (alive > 3 years) and those with poor outcome (dead < 2 years) within data from The Cancer Genome Atlas (TCGA). The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) turned out as the only gene with differential expression in these groups. In order to further investigation on its role in OvCa, we analyzed CEACAM1 mRNA levels extracted from TCGA microarray data (n = 517) as well as CEACAM1 protein expression by Western blot analysis in a cohort of 242 tumor samples. Further, CEACAM1 localization in tumour tissue was evaluated by immunohistochemistry and CEACAM1 splice variants by RT-PCR in representative tumours. In Kaplan–Meier analysis, high CEACAM1 mRNA levels significantly correlated with longer survival (p = 0.008). By Western blot analysis in the second cohort, similar associations of high CEACAM1 protein levels with longer recurrence-free survival (RFS, p = 0.035) and overall survival (OAS, p = 0.004) were observed. In multivariate Cox regression analysis including clinical prognostic parameters, CEACAM1 mRNA or protein expression turned out as independent prognostic markers. Stratified survival analysis showed that high CEACAM1 protein expression was prognostic in node-negative tumors (p = 0.045 and p = 0.0002 for DFS and OAS) but lost prognostic significance in node-positive carcinomas. Similarly, high CEACAM1 mRNA expression did not show prognostic relevance in tumors with lymphatic invasion (L1) but was associated with longer survival in cases without lymphovascular involvement. Further analysis showed a predominance of 4S and 4L isoforms and mostly membraneous CEACAM1 localization in ovarian tumours. Our results suggest that CEACAM1 might be an independent favorable prognostic marker in OvCa, especially in the subgroup of patients with solely intraperitoneal metastasis.

Highlights

Epithelial ovarian carcinoma (EOC) is the gynecologic tumor with the highest mortality
Our results suggest that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) might be an independent favorable prognostic marker in ovarian cancer (OvCa), especially in the subgroup of patients with solely intraperitoneal metastasis
Li et al have recently shown a membrane-associated CEACAM1 staining in primary lowgrade adenocarcinomas, whereas in high-grade adenocarcinomas and metastatic lesions CEACAM1 were mainly localized in the cytoplasm

Summary

Introduction

Epithelial ovarian carcinoma (EOC) is the gynecologic tumor with the highest mortality. The specific role of concrete isoforms has been studied by different groups in melanoma and colon cancer [15,16,17]. Li et al have recently shown a membrane-associated CEACAM1 staining in primary lowgrade adenocarcinomas, whereas in high-grade adenocarcinomas and metastatic lesions CEACAM1 were mainly localized in the cytoplasm. These data suggest a tumor suppressor function of membranous CEACAM1, while cytoplasmic CEACAM1 might be involved in tumor progression and metastasis [18]. In order to deeply evaluate the relevance of CEACAM1 for ovarian cancer progression, we analyzed its predictive and prognostic value at both the mRNA and protein level in two well-characterized ovarian cancer cohorts

Material and Methods

Results

Discussion

Conclusion