Abstract 4925: Plasma levels of cartilage oligomeric matrix protein (COMP), are significantly increased in patients with colorectal cancer

Abstract

Abstract Introduction: Cartilage Oligomeric Matrix Protein (COMP) is a member of the thrombospondin family of extracellular calcium-binding proteins that plays role in the assembly of extracellular matrix. COMP maintains the structural integrity of cartilage through its interaction with a number of extracellular matrix proteins. COMP has a unique binding site for Vitamin D, indicating that it may also participate in storage and delivery of cell-signaling molecules. An expression array analysis of colorectal cancer samples vs normal tissue has noted overexpression of COMP mRNA. This study was undertaken to assess preoperative blood levels of COMP in the setting of colorectal cancer(CRC). Our hypothesis is that plasma levels of COMP may be elevated due to tumor overexpression and that this protein may have potential as a diagnostic marker for colorectal cancer. Method: Patients (pts) undergoing elective colorectal resection for CRC or benign colonic pathology (BCP) that had been prospectively enrolled in an IRB approved tissue and data bank for whom adequate PreOp plasma samples were available were studied. Demographic, clinical, and pathologic data were collected. Plasma COMP levels were determined via ELISA in duplicate and are reported as median +95%CI (ng/ml). Tissue expression levels were determined in paired tumor and normal tissue samples of a subpopulation of study pts by QRT-PCR .The candidacy of COMP as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Wilcoxon/Kruskal-Wallis test was used for statistical analysis, (significance p<0.05). Results: A total of 151 CRC (73%colon, 27%rectal) and 73 BCP pats (Adenoma 21%, diverticulitis 57%, other 22%) were studied. The male/female ratios were similar. The CRC stage distribution was: Stage 1, 22%; Stage 2, 32%; Stage 3, 31%; and Stage 4, 15%. The median plasma COMP levels were significantly higher in the CRC pts (209.2,CI: 187.8,234) vs. the BCP pats(129.6,CI: 110.7,149.2; P = < 0.0001). The plasma COMP levels were significantly higher in Stage III pts. (p = 0.001) and in Stage II+III pats. (p = 0.03) compared to Stage I pts. The AUC value for the ROC curve was 0.781 (sensitivity 53%, specificity 93%). Increased expression of COMP was noted in 59% of the CRC tissue samples tested (10/17) vs. paired normal tissue samples. Conclusion: The CRC median plasma COMP level was 61% higher than the median BCP result and the Stage 3 median level 50% higher than the median Stage I level. In general, plasma COMP levels increased with advancing cancer stage. The AUC results suggest COMP may have value as a CRC prognostic marker, perhaps, in combination with other protein markers to increase the sensitivity. Tissue expression analysis suggests that the most likely source of the added COMP in the plasma is the tumor itself. Further study with larger populations of control and CRC pts is warranted. Citation Format: Hmc Shantha Kumara, Hiromichi Miyagaki, Xiaohong Yan, Linda Njoh, Vesna Cekic, Nipa D. Gandhi, Melissa M. Alvarez-Downing, Richard L. Whelan. Plasma levels of cartilage oligomeric matrix protein (COMP), are significantly increased in patients with colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4925.