Prognostic Significance of CD26 in Patients with Colorectal Cancer

Abstract

BackgroundCD26, dipeptidyl peptidase IV, was discovered firstly as a membrane-associated peptidase on the surface of leukocyte. We previously demonstrated that a subpopulation of CD26+ cells were associated with the development of distant metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC). In order to understand the clinical impact of CD26, the expression was investigated in CRC patient's specimens. This study investigated the prognostic significance of tumour CD26 expression in patients with CRC. Examination of CD26+ cells has significant clinical impact for the prediction of distant metastasis development in colorectal cancer, and could be used as a selection criterion for further therapy.MethodsTumour CD26 expression levels were studied by immunohistochemistry using Formalin-fixed paraffin embedded (FFPE) tissues in 143 patients with CRC. Tumour CD26 expression levels were correlated with clinicopathological features of the CRC patients. The prognostic significance of tumour tissue CD26 expression levels was assessed by univariate and multivariate analyses.ResultCD26 expression levels in CRC patients with distant metastasis were significantly higher than those in non-metastatic. High expression levels of CD26 were significantly associated with advanced tumour staging. Patients with a high CD26 expression level had significantly worse overall survival than those with a lower level (p<0.001).ConclusionsThe expression of CD26 was positively associated with clinicopathological correlation such as TNM staging, degree of differentiation and development of metastasis. A high CD26 expression level is a predictor of poor outcome after resection of CRC. CD26 may be a useful prognostic marker in patients with CRC.

Emergence of CD26+ Cancer Stem Cells with Metastatic Properties in Colorectal Carcinogenesis

“…We have also shown that CD26+ correlates with the clinical stage on immunohistochemistry [4]. This study shows that confirmed or suspected stage IV primary tumors have a relatively large CD26+ subpopulation, while in stage I to III disease there is no apparent trend of the CD26+ population increasing with the increase of the disease stage.…”

The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity

“…Beyond diabetes, the role of DPP4 has been widely studied in several types of cancer, including CRC. The expression of DPP4 correlated with the populations of cancer stem cells and poor survival in human CRC (Lam et al, 2014;Pang et al, 2010). DPP4 has peptidase activity and is able to cleave and degrade many biologically active peptides (Tanaka et al, 1992).…”

“…Our current data also support an emerging anticancer strategy and suggest that pharmacological induction of ferroptosis may be effective in genotype-selected subgroups of CRC patients. In particular, the presence of two genotypes associated with poor prognosis in CRC-namely, TP53 mutation/ deletion (Fearon, 2011) combined with DPP4 overexpression (Lam et al, 2014) -is likely to characterize a target population that would profit from treatment with erastin and perhaps other yet-to-be-developed ferroptosis inducers. Identification and characterization of unknown nuclear localization signals in DPP4 could be important in understanding the locationdependent role of DPP4 in ferroptosis.…”

A poor prognosis in human hepatocellular carcinoma is associated with low expression of DPP4

“…However, there is variability between various forms of cancers regarding the efficacy of DPP4 (8). DPP4 is upregulated in many aggressive types of T-cell malignancies (9), esophageal adenocarcinoma (10), lung adenocarcinoma (11), thyroid carcinoma (12), and prostate cancer (13), and a high level of DPP4 is indicative of poor prognosis for papillary thyroid carcinoma (14), urothelial carcinoma (15), and colorectal cancer (16). In contrast, DPP4 is downregulated in tissues of liver cirrhosis (17), endometrial adenocarcinoma tissues (18), and a low serum level of DPP4 was related to a poor prognosis for patients who have esophageal squamous cell carcinoma (19).…”