Dipeptidyl peptidase 10, a novel prognostic marker in colorectal cancer

Abstract

Purpose: The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood.

Materials and methods: The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes.

Results: DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008).

Conclusion: DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.

Keywords: Colorectal cancer; dipeptidyl peptidase 10; prognosis; progression.

Fig. 1

Immunohistochemistry of DPPIV in primary colorectal cancers (×200). (A) Normal crypt epithelium did not express DPPIV protein. (B) Some colorectal cancers showed intraluminal expression of DPPIV. (C) Rare colorectal cancers showed focal cytoplasmic expression of DPPIV. DPPIV, dipeptidyl peptidase IV.

Fig. 2

Immunohistochemistry of DPP10 in primary colorectal cancers (×200). (A) Normal crypt epithelium showed mild DPP10 expression in cytoplasm. (B) Most colorectal cancers retained DPP10 expression. (C) Some colorectal cancers showed loss of DPP10 expression. DPP, dipeptidyl peptidase.

Fig. 3

Kaplan-Meier survival curves according to the DPP10 expression in 383 colorectal cancer patients. Loss of DPP10 expression in primary tumor was significantly associated with worse cancer-specific (A) and progression-free (B) survival. DPP, dipeptidyl peptidase.

Fig. 4

Western blot of DPP10 in 10 colorectal cancer patients with synchronous liver metastasis. (A) Western blotting of matched normal colon, primary colorectal cancer, and liver metastasis from 10 selected patients showed variable expression of DPP10. (B) Level of expression of DPP10 in primary colorectal cancer was significantly decreased. N, normal; T, tumor; DPP, dipeptidyl peptidase; OD, optical density.