Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

Abstract

BackgroundProstate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value.Methodology/Principal FindingsWe first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7–8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men.Conclusion/SignificanceSPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA.

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“…Up-regulation of genes coding for ECM proteins was also a feature in BM-MSC exposed to MLL/ENL+FLT3-ITD leukemia (both Trp53 wt and Trp53 -/-), with BMP1, SPON2, and TGM2 being the most prominent. SPON2 and its translational product, Spondin-2, have been found to be up-regulated in many types of cancer [37][38][39], and its expression is a prognostic factor in prostate and colorectal cancer [40,41]. In breast cancer, expression of TGM2 in tumor stroma is an independent risk factor for breast cancer patients at high risk of recurrence [42].…”

The molecular signature of AML mesenchymal stromal cells reveals candidate genes related to the leukemogenic process

“…In this study, the WNT pathway could regulate BMP4 expression. BMP4 is a protein secreted into the bone marrow microenvironment, and decreased BMP4 expression may result a disruption of HSC function [20].…”

“…CCL2 and MMP16 were selected because they are related to the bone marrow microenvironment and to AML [17,18]. BMP4 and SSP1 genes are important for the development and maintenance of HSCs [15,19], and SPOND2 and CLDN1 were chosen because they are related to neoplasia [20,21]. The RT-qPCR results presented in Fig.…”

Anterior gradient 2: A novel sensitive tumor marker for metastatic oral cancer

“…For instance, SPON2 is a cell adhesion protein, which has been shown to improve cell migration and invasion as well as act as a diagnostic biomarker for human liver carcinoma and prostate cancer [36,37]. TXNIP is a thioredoxin binding protein that generates oxidative stress for regulation of anti-proliferation and the cell cycle in leukemia cells [37,38].…”