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

Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay.
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通过高型免疫测定法发现了CASP8作为高风险前列腺癌的潜在生物标志物。

DOI:
10.1038/s41598-021-87155-5
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发表时间:
2021-04-07
期刊:
影响因子:
4.6
通讯作者:
Stoyanova T
Stoyanova T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu S;Garcia-Marques F;Zhang CA;Lee JJ;Nolley R;Shen M;Hsu EC;Aslan M;Koul K;Pitteri SJ;Brooks JD;Stoyanova T

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前列腺癌仍然是美国男性中最常见的非皮肤恶性肿瘤。为了发现高风险前列腺癌的潜在血清生物标志物,我们利用来自 10 名患有高级别和高容量前列腺癌的男性的患者匹配的术前和术后血清样本进行了高多重免疫测定。我们的研究确定了 174 种蛋白质中的 6 种(CASP8、MSLN、FGFBP1、ICOLSG、TIE2 和 S100A4)在根治性前列腺切除术后显着减少。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。通过免疫组织化学分析,与非癌组织和 BPH 组织相比,CASP8 蛋白在前列腺癌组织中表达水平较高。同样,在四个独立的临床数据集中,与良性前列腺组织相比,前列腺癌中的 CASP8 mRNA 表达显着上调。此外,与非复发性前列腺癌患者相比,复发性前列腺癌患者的 CASP8 mRNA 水平较高,并且 CASP8 的高表达与肾癌较差的无病生存期和总生存期相关。总之,我们的结果表明 CASP8 可能作为高风险前列腺癌和肾癌的生物标志物。
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.
前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
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