SIGIRR/TIR8, an important regulator of TLR4 and IL-1R-mediated NF-κB activation, predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas.
SIGIRR/TIR8, an important regulator of TLR4 and IL-1R-mediated NF-κB activation, predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas.
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DOI：
10.1016/j.humpath.2015.07.015
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发表时间：
2015-11
期刊：
影响因子：
3.3
通讯作者：
Ricke WA
中科院分区：
文献类型：
--
作者：
Bauman TM;Becka AJ;Sehgal PD;Huang W;Ricke WA
单个IG IL-1相关受体（SIGIRR）是Toll样受体（TLR）4和IL-1介导的活化B细胞核因子κ轻链增强子（NF-κB）活化的负调节因子。本研究的目的是定性和定量测定SIGIRR蛋白在人前列腺组织中的表达，并将SIGIRR表达与临床参数相关联。使用免疫组织化学和多光谱成像在腺前列腺组织中定量SIGIRR表达，并评价其与良性前列腺增生（BPH）和前列腺癌（PCa）的临床病理特征的关系。低Gleason评分（≤6和3+4）和高Gleason评分（4+3和≥8）亚组用于患者结局。SIGIRR主要在前列腺上皮细胞的细胞质和细胞核中表达，在间质中几乎没有表达。与正常前列腺相比，前列腺增生、高级别前列腺上皮内瘤变（HGPIN）、前列腺癌和转移瘤的胞浆SIGIRR表达相似。在转移样品中发现核表达减少（p=0.04）。SIGIRR表达的变化与Gleason评分、病理分期、肿瘤体积、手术切缘状态或血清前列腺特异性抗原（PSA; p>0.05）无关。在单变量分析中，细胞核（p =0.96）和细胞质（p=0.89）SIGIRR表达与患者结局无关，但在低Gleason评分患者分析中，细胞质SIGIRR高表达与单变量（p=0.01）和多变量（HR 2.31 [95%CI 1.05-5.06] p=0.04）分析中的生化复发相关。类似地，在仅低分期（pT 2）肿瘤的多变量分析中，SIGIRR独立预测生化复发（p=0.009）。我们得出的结论是，SIGIRR可以预测低格里森评分和低病理分期前列腺癌患者的生化复发。
Single Ig IL-1-related receptor (SIGIRR) is a negative regulator of toll-like receptor (TLR) 4 and IL-1 mediated activation of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). The purpose of this study was to qualitatively and quantitatively determine SIGIRR protein expression in human prostate tissues and associate SIGIRR expression with clinical parameters. SIGIRR expression was quantified in glandular prostate tissue using immunohistochemistry and multispectral imaging, and expression was evaluated in relation to clinico-pathological features of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Subgroupings of low Gleason score (≤6 and 3+4) and high Gleason score (4+3 and ≥8) were used for patient outcomes. SIGIRR was predominantly expressed in the cytoplasm and nucleus of the prostatic epithelium with little expression within the stroma. Compared to normal prostate, cytoplasmic SIGIRR expression was similar in BPH, high-grade prostatic intraepithelial neoplasia (HGPIN), PCa, and metastases. A decrease in nuclear expression was found in metastasis samples (p=0.04). Changes in SIGIRR expression were not associated with Gleason score, pathologic stage, tumor volume, surgical margin status, or serum prostate-specific antigen (PSA; p>0.05). Nuclear (p=0.96) and cytoplasmic (p=0.89) SIGIRR expression were not related to patient outcomes in univariable analysis, but in analysis of patients with low Gleason scores, high cytoplasmic SIGIRR expression was associated with biochemical recurrence in both univariable (p=0.01) and multivariable (HR 2.31 [95% CI 1.05–5.06] p=0.04) analysis. Similarly, in multivariable analysis of only low stage (pT2) tumors, SIGIRR independently predicted biochemical recurrence (p=0.009). We conclude that SIGIRR predicts biochemical recurrence in patients with low Gleason score and low pathological stage prostate cancer.