Deleted in malignant brain tumor 1 is a novel prognostic marker in colorectal cancer.

Abstract

The gene deleted in malignant brain tumor1 (DMBT1) encoding a large scavenger receptor cysteine-rich protein was originally identified based on its deletion in a brain tumor cell line. The DMBT1 protein is involved in mucosal immune defense, epithelial differentiation and tumor suppression. In the present study, the clinicopathologic significance of DMBT1 protein expression in stool and tissue samples of colorectal cancer(CRC) patients was evaluated. Western blot analysis of fecal DMBT1 was performed for patients with CRC(n=177), colorectal adenoma(n=61), inflammatory bowel diseases(IBDs;n=54) and healthy individuals as the control group(n=151). Immunohistochemical analysis of tissue expression of DMBT1 was performed in 385primary CRC tissues. Fecal DMBT1 expression was higher in CRC and IBD patients than in healthy controls or adenoma patients (P<0.0001), but not significantly different between IBD and CRC or between adenoma and healthy control groups. In CRC patients, fecal DMBT1 expression was not associated with the tumor stage or site. The sensitivity of fecal DMBT1 analysis for CRC was50%, while the specificity and positive predictive value were86.8 and81.3%, respectively. Immunohistochemical expression patterns of DMBT1 in CRC tissues varied from loss to overexpression. Loss of expression was observed in 4.7%(18outof385cases) and significantly associated with lymph node metastasis(P=0.016), distant metastasis(P=0.013), advanced stage(P=0.026), and higher histologic grade(P=0.033). In addition, DMBT1 loss was an independent poor prognostic factor for cancer-associated death (hazard ratio,2.272;P=0.015) and disease recurrence (hazard ratio,2.689;P=0.009). In conclusion, fecal DMBT1 has limited value as a diagnostic biomarker, while the tissue expression of DMBT1 may serve as an efficient prognostic marker for CRC. Furthermore, DMBT1 may have a role in the progression of CRC.