P-Cadherin (CDH3) is overexpressed in colorectal tumors and has potential as a serum marker for colorectal cancer monitoring
H.M.C. Shantha Kumara1, Geoffrey A. Bellini1, Otavia L. Caballero2,5, Sonali A.C. Herath1, Tao Su3, Aqeel Ahmed3, Linda Njoh1, Vesna Cekic1, Richard L. Whelan1,4
1 Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai Roosevelt Hospital Center, New York, NY, USA
2 Ludwig Institute for Cancer Research Ltd, New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering, New York, NY, USA
3 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA
4Icahn School of Medicine at Mount Sinai, New York, NY, USA
5 Current address: Orygen Biotecnologia, S.A., São Paulo, Brazil
Correspondence to:
Richard L. Whelan, email: [email protected]
Keywords: CDH3, colorectal cancer, immunotherapy target
Received: August 23, 2017 Accepted: September 29, 2017 Published: October 21, 2017
Abstract
Introduction: Placental-Cadherin (CDH3) is a cell adhesion molecule vital to cellular localization and tissue integrity. It is highly expressed in the placenta (PLC)and is overexpressed by many types of cancer. P-cadherin levels in colorectal cancer (CRC) remains poorly characterized. This study’s purpose was to determine P-cadherin expression in CRC and normal tissues and to assess plasma CDH3 levels in order to determine the relationship, if any, between cancer stage, P-cadherin expression and plasma CDH3 levels. Methods: An IRB approved plasma, tumor, and prospective data bank was utilized. CRC patients for whom tumor and normal colon tissue samples were available were enrolled. Tumor samples were OCT embedded and stored at -80C°. Total purified RNA was isolated from tissue samples and cDNA synthesized. CDH3 expression was analyzed by quantitative PCR (QPCR) using the SYBR Green platform. Tumor expression levels were determined and compared to levels in normal colonic tissue and PLC. Expression in 22 different normal tissues was also assessed by RT-PCR. Plasma CDH3 levels were determined via ELISA in patients for whom preoperative blood samples were available. Results: A total of 77 paired CRC and normal colon specimens (36 M/ 41 F, age 67.3±14.5) were assessed (82% colon, 18% rectal; Cancer Stage 2, 44; Stage 3, 33). All tested tumors had CDH3 expression levels over 0.1% of the PLC level and tumor to normal colon ratios greater than 1. CDH3 expression was noted in 14/22 normal organ tissues. There was a positive correlation between tumor CDH3 QPCR and preoperative CDH3 blood levels (n=57, P= 0.038). Expression levels were significantly higher in rectal vs. colon tumors (p=0.019). Conclusion: CDH3 expression was elevated in CRC tumors as compared to normal tissue. CDH3 was expressed by numerous normal organs and, thus, is not a viable vaccine target, however, the correlation between plasma and tumor CDH3 levels suggests CDH3 may have value as a diagnostic or prognostic marker.
