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

Abstract

The gene deleted in malignant brain tumor 1 (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 385 primary 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 was 50%, while the specificity and positive predictive value were 86.8 and 81.3%, respectively. Immunohistochemical expression patterns of DMBT1 in CRC tissues varied from loss to overexpression. Loss of expression was observed in 4.7% (18 out of 385 cases) 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.

The protective role of DMBT1 in cervical squamous cell carcinoma

“…Besides, down‐expressed DMBT1 in invasive cholangiocarcinoma demonstrated the late stage of cholangiocarcinogenesis . In another study, LOH on marker D10S209 near the DMBT1 loci was observed to be a significantly poor prognostic factor, and DMBT1 loss in colorectal cancer was an independent unfavorable prognostic factor for cancer‐associated death and disease recurrence . Moreover, CSCC patients with positive DMBT1 expression had apparently higher 5‐year survival rate than those with negative DMBT1 expression in our study, suggesting that DMBT1 may not only participate in the progression of CSCC, but affect the prognosis of CSCC.…”

“…26 In another study, LOH on marker D10S209 near the DMBT1 loci was observed to be a significantly poor prognostic factor, 27 and DMBT1 loss in colorectal cancer was an independent unfavorable prognostic factor for cancer-associated death and disease recurrence. 28 Moreover, CSCC patients with positive DMBT1 expression had apparently higher 5-year survival rate than those with negative DMBT1 expression in our study, suggesting that DMBT1 may not only participate in the progression of CSCC, but affect the prognosis of CSCC. It was worth noting that the 5-year survival for stage II patients was indeed lower than expectation, which may be affected the multiple factors, including the small sample size (n = 37), severe stage (stage IIB: n = 27, stage IIA: n = 11), DMBT1 expression (negative: n = 36; positive: n = 1), and so on.…”

Immunohistochemical Localization of Deleted in Malignant Brain Tumors 1 in Normal Human Tissues

“…18 Loss of DMBT1 is associated with an increased risk of Crohn’s disease, metastasis, and cancer-associated death. 19–21 High expression of DMBT1 promotes apoptosis of cancer cells in vitro and inhibits tumor progression in vivo. 22…”

Anti-proliferative mechanism of Huaier extract in human thyroid carcinoma cells

“…Speci cally, DMBT1 was the most downregulated transcript, with a 133.4784-fold reduction, and ZNF780B was the most upregulated transcript, with the greatest fold change of 1657.641. Additionally, it has been reported that the overexpression of DMBT1 is related to biliary carcinoma [23] and colorectal cancer [24]. Moreover, ZNF780B expression has been correlated with hepatocellular carcinoma [25] and primary osteoarthritis [26].…”