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通过高多重免疫分析发现 CASP8 作为高危前列腺癌的潜在生物标志物。

Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay.

机构信息

Department of Radiology, Stanford University, Stanford, CA, USA.

Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, USA.

出版信息

Sci Rep. 2021 Apr 7;11(1):7612. doi: 10.1038/s41598-021-87155-5.

DOI:10.1038/s41598-021-87155-5
PMID:33828176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8027881/
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.

摘要

在美国，前列腺癌仍然是男性中最常见的非皮肤恶性肿瘤。为了发现高危前列腺癌的潜在血清生物标志物，我们利用 10 名患有高级别和大容量前列腺癌的男性患者的术前和术后配对血清样本进行了高多重免疫测定。我们的研究从 174 种蛋白质中鉴定出了六种（CASP8、MSLN、FGFBP1、ICOSLG、TIE2 和 S100A4），这些蛋白质在根治性前列腺切除术后显著减少。与术后血清样本和良性前列腺增生（BPH）患者的血清样本相比，术前血清样本中检测到高水平的 CASP8。通过免疫组织化学，与非癌组织和 BPH 组织相比，前列腺癌组织中 CASP8 蛋白表达水平更高。同样，在四个独立的临床数据集，与良性前列腺组织相比，前列腺癌中 CASP8mRNA 的表达显著上调。此外，与无复发生存和总生存率相关的是，与无复发性前列腺癌患者相比，复发性前列腺癌患者的 CASP8mRNA 水平更高，并且肾细胞癌中 CASP8 的高表达与无复发生存和总生存率相关。总之，我们的研究结果表明，CASP8 可能是高危前列腺癌和可能的肾癌的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/115442fa0889/41598_2021_87155_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/522db9f9b684/41598_2021_87155_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/64dfe41d7c04/41598_2021_87155_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/1c12918fa268/41598_2021_87155_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/115442fa0889/41598_2021_87155_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/522db9f9b684/41598_2021_87155_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/64dfe41d7c04/41598_2021_87155_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/1c12918fa268/41598_2021_87155_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5550/8027881/115442fa0889/41598_2021_87155_Fig4_HTML.jpg

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