Abstract
Prostate cancer remains the most common non-cutaneous malignancy among men in the United States. To discover potential serum-based biomarkers for high-risk prostate cancer, we performed a high-multiplex immunoassay utilizing patient-matched pre-operative and post-operative serum samples from ten men with high-grade and high-volume prostate cancer. Our study identified six (CASP8, MSLN, FGFBP1, ICOSLG, TIE2 and S100A4) out of 174 proteins that were significantly decreased after radical prostatectomy. High levels of CASP8 were detected in pre-operative serum samples when compared to post-operative serum samples and serum samples from patients with benign prostate hyperplasia (BPH). By immunohistochemistry, CASP8 protein was expressed at higher levels in prostate cancer tissues compared to non-cancerous and BPH tissues. Likewise, CASP8 mRNA expression was significantly upregulated in prostate cancer when compared to benign prostate tissues in four independent clinical datasets. In addition, mRNA levels of CASP8 were higher in patients with recurrent prostate cancer when compared to patients with non-recurrent prostate cancer and high expression of CASP8 was associated with worse disease-free survival and overall survival in renal cancer. Together, our results suggest that CASP8 may potentially serve as a biomarker for high-risk prostate cancer and possibly renal cancer.
Highlights
Prostate cancer remains the most common non-cutaneous malignancy among men in the United States
CASP8, S100A4, MSLN, FGFBP1, ICOSLG, and TIE2 were found significantly decreased after radical prostatectomy (Fig. 1B–E)
By performing a screen for proteins in pre-operative and post-operative serum from men with high-risk prostate cancer, we identified CASP8, MSLN, FGFBP1, ICOSLG, TIE2, and S100A4 proteins as candidate biomarkers for high-risk prostate cancer
Summary
Prostate cancer remains the most common non-cutaneous malignancy among men in the United States. To discover potential serum-based biomarkers for high-risk prostate cancer, we performed a high-multiplex immunoassay utilizing patient-matched pre-operative and post-operative serum samples from ten men with high-grade and high-volume prostate cancer. To identify new biomarkers for high-risk prostate cancer, we compared protein levels in pre-operative to post-operative serum samples from ten men with highgrade and high-volume prostate cancer by a high-multiplex immunoassay. We utilized pre-operative and post-operative serum from patients with high-risk prostate cancer (Gleason grade 4 + 5) to identify prostate cancer specific biomarkers and minimize changes in serum proteins due to patient heterogeneity including genetic background, age, pre-operative PSA levels, and other underlying medical conditions. Our study identified CASP8 as a promising protein biomarker for detection of high-risk prostate cancer and potentially renal cancer
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