Prognostic role of serum AZGP1, PEDF and PRDX2 in colorectal cancer patients

Abstract

This study was designed to develop novel and better reliable serum prognostic biomarkers for colorectal cancer (CRC). A 50 sample set including CRC, adenoma and healthy control sera was used to identify the serum proteins involved in CRC carcinogenesis using serum proteomic approach. Alpha-2-glycoprotein 1, zinc-binding (AZGP1), pigment epithelium derived factor (PEDF) and peroxiredoxin 2 (PRDX2) were selected as good candidates. Two independent cohorts of 868 individuals were enrolled. The expression of selected proteins in serum from cohort 1 (n = 534) was quantified with enzyme-linked immunosorbent assays. CRC sera of this cohort (n = 405) were assigned to training and test sets, which were used to identify and verify the prognostic markers. The prognostic values of identified proteins were further validated in cohort 2 (n = 334) using quantitative reverse transcription PCR and immunohistochemical staining. Our data showed that the elevated AZGP1 and decreased PEDF and PRDX2 expressions in CRC serum and tissues were correlated with liver metastases. In the training set, higher AZGP1 and lower PEDF levels in sera were significantly associated with a poorer overall survival (OS), higher AZGP1 was also associated with a poorer disease-free survival (DFS). This association was verified in the testing set and further validated in patients in cohort 2. Patients with lower PEDF or PRDX2 levels in their CRC tissues had a significantly poorer DFS or OS than patients with high levels of these proteins in cohort 2. Univariate and multivariate analyses indicated that the prognostic performance of serum AZGP1 and PEDF was independent of other clinicopathological factors. We propose that they may serve as prognostic markers and potential therapeutic targets in CRC.

Reduction of AZGP1 predicts poor prognosis in esophageal squamous cell carcinoma patients in Northern China

“…In the past, a number of studies confirmed that AZGP1 downregulation was relevant to poor prognosis, which has been identified as a predictor of prognosis in various malignant tumors 24,27–30. In lung adenocarcinoma and prostate cancer, patients with low levels of AZGP1 were reported to be associated with worse survival than those with high levels of AZGP1 26,31.…”

Alpha-2-Glycoprotein 1(AZGP1) Regulates Biological Behaviors of LoVo Cells by Down-Regulating mTOR Signaling Pathway and Endogenous Fatty Acid Synthesis

“…Moreover, a gene silencing study clearly showed that AZGP1 might act as a novel tumor suppressor gene in pancreatic cancer [11]. Interestingly, high-level expression of AZGP1 has been associated with poor prognosis and could potentially be potential a marker for the diagnosis of colorectal cancer [12], [13]. However, the underlying mechanism of AZGP1 remains unknown.…”

“…Moreover, AZGP1 has been identified as a prognostic marker for prostate cancer [7], breast cancer [8], [9], and gastric cancer [10], and it acts as a novel tumor suppressor in pancreatic cancer [11]. Recently researchers have identified that AZGP1 could also be a potential marker for diagnosis and prognosis of colorectal cancer [12], [13]. However, the role of AZPG1 in colorectal cancer is currently unknown.…”

The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development

“…In this manner, Prx2 plays a role in cytokine mediated inflammatory signaling. The serum levels of Prx2 in colorectal cancer are correlated with the survival of patients [105]. In human papillomavirus (HPV) related cervical cancer, increased expression of Prx2 is proposed to mediate the carcinogenesis in cervical tissue [106; 107].…”