Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery

<p>Abstract</p> <p>Background</p> <p>There is an important need for the identification of novel serological biomarkers for the early detection of cancer. Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics.</p> <p>Methods</p> <p>Previous studies have focused on either gene or protein expression databases for the identification of candidates. We developed a strategy that mines six publicly available gene and protein databases for tissue-specific proteins, selects proteins likely to enter the circulation, and integrates proteomic datasets enriched for the cancer secretome to prioritize candidates for further verification and validation studies.</p> <p>Results</p> <p>Using colon, lung, pancreatic and prostate cancer as case examples, we identified 48 candidate tissue-specific biomarkers, of which 14 have been previously studied as biomarkers of cancer or benign disease. Twenty-six candidate biomarkers for these four cancer types are proposed.</p> <p>Conclusions</p> <p>We present a novel strategy using bioinformatics to identify tissue-specific proteins that are potential cancer serum biomarkers. Investigation of the 26 candidates in disease states of the organs is warranted.</p

Expression of redox pathway enzymes in human prostatic tissue.

OBJECTIVE: To evaluate the involvement of thioredoxin reductase (TxnR), thioredoxin (Trx) and peroxiredoxins (Prdx) in prostate cancer (PCa) and to assess the potential prognostic importance of these redox-regulated pathways. STUDY DESIGN: Expression of the isoforms TxnR2, Trx1 and Prdx2 was studied by immunohistochemistry on tissue microarrays (TMAs). In a prognostic TMA, 294 primary cases of PCa with a median follow-up of 49 months were stained for Trx1 and Prdx2. Another TMA containing benign prostatic tissue, atrophy, high grade prostatic intraepithelial neoplasia (HGPIN) and PCa from 40 patients was stained with all 3 antibodies. RES ULTS: All 3 proteins showed similar expression patterns, with the highest immunoreactivity in HGPIN followed by atrophy, PCa and benign tissue. TxnR2, Trx1 and Prdx2 were overexpressed in HGPIN and PCa compared with benign tissue (p < 0.001), and Trx1 and Prdx2 were also overexpressed in HGPIN compared with PCa (p < 0.001). Trx1 and Prdx2 did not correlate with biochemical recurrence. CONCLUSION: This study demonstrates up-regulation of the redox pathway proteins in PCa and its precursor lesions. The pathogenetic role of the redox system remains to be investigated