Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

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.

A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients

“…Due to its inhibitory functions in immune cells including T and NK cells, in addition to being expressed on tumor cells, CEACAM1 makes a promising target for immunotherapy [41]. High expression of CEACAM1 correlates with better prognosis in advanced ovarian cancer patients, suggesting a tumor suppressor function in ovarian cancer [42]. In the current study plasma levels of CEACAM1 were lower in patients with cancer compared to benign tumors, supporting the role of CEACAM1 as a tumor suppressor.…”

Up‐regulation of microRNA‐30b/30d cluster represses hepatocyte apoptosis in mice with fulminant hepatic failure by inhibiting CEACAM1

“…25 Another essential finding in our study illuminated that reduction of miR-30b and miR-30d, and elevation of CEACAM1 indicated a poor prognosis of FHF. Similar to this finding, CEACAM1 has been reported to be a prognostic marker of node-negative ovarian cancer, 26 oral squamous cell carcinoma and carcinoma in situ, 27 and high CEACAM1 expression was inversely related to overall and disease-specific five-year survival. The prognostic role of miR-30b has been verified in NSCLC.…”

Combined inhibition of PD-1/PD-L1, Lag-3, and Tim-3 axes augments antitumor immunity in gastric cancer–T cell coculture models

“…Expression of each inhibitory ligand was assessed by the TPS. TPS ≥ 10% was used for PD-L1 and standardized at ≥ 25% for MHC class II (25% used in [ 21 ]), CEACAM-1 (20–30% used in [ 22 , 23 ]) and LSECtin (no report on TPS).…”