Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

TY - JOUR

T1 - Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

AU - Oliveira-Ferrer, Leticia

AU - Goswami, Roshni

AU - Galatenko, Vladimir

AU - Ding, Yi

AU - Eylmann, Kathrin

AU - Legler, Karen

AU - Kürti, Sascha

AU - Schmalfeldt, Barbara

AU - Milde-Langosch, Karin

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Antigens, CD

KW - Biomarkers, Tumor

KW - Carcinoma

KW - Cell Adhesion Molecules

KW - Female

KW - Humans

KW - Lymphatic Metastasis

KW - Middle Aged

KW - Ovarian Neoplasms

KW - Protein Isoforms

KW - Journal Article

U2 - 10.1155/2018/6714287

DO - 10.1155/2018/6714287

M3 - SCORING: Journal article

C2 - 30050594

VL - 2018

SP - 6714287

JO - DIS MARKERS

JF - DIS MARKERS

SN - 0278-0240

ER -