Expression of Indoleamine 2,3-Dioxygenase Induced by IFN-γ and TNF-α as Potential Biomarker of Prostate Cancer Progression.
Expression of Indoleamine 2,3-Dioxygenase Induced by IFN-γ and TNF-α as Potential Biomarker of Prostate Cancer Progression.
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DOI：
10.3389/fimmu.2018.01051
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发表时间：
2018
影响因子：
7.3
通讯作者：
Provenzano M
中科院分区：
文献类型：
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作者：
Banzola I;Mengus C;Wyler S;Hudolin T;Manzella G;Chiarugi A;Boldorini R;Sais G;Schmidli TS;Chiffi G;Bachmann A;Sulser T;Spagnoli GC;Provenzano M
炎症被认为在前列腺癌（PCa）的发病和进展中发挥重要作用。前列腺切除标本的组织学分析揭示了这种恶性肿瘤早期病变的局灶性炎症。我们探讨了炎症刺激在 PCa 特异性、肿瘤源性可溶性因子 (PCa-TDSF) 释放中的作用，据报道，这些因子是 PCa 发病的介质，例如吲哚胺 2,3-双加氧酶 (IDO) 和白细胞介素 (IL)-6。通过用 IFN-γ 或 TNF-α 刺激已建立的细胞系（CA-HPV-10 和 PC3），“体外”测试了 PCa-TDFS 的炎症驱动的产生和功能。与良性前列腺增生 (BPH) 标本相比，研究了接受根治性前列腺切除术的 PCa 患者肿瘤组织中编码 IDO、IL-6、IFN-γ、TNF-α 及其受体的基因的表达。 IFN-γ和TNF-α治疗导致已建立的细胞系中诱导IDO和IL-6基因表达和释放，这表明这些细胞因子诱导PCa-TDSF可能导致癌症进展为无法治疗的表型。基于生化复发时间的分析揭示了 IDO 而不是 IL-6 基因表达在预测 PCa 患者无复发生存 (RFS) 方面的预后价值。此外，一项基于尿液的 mRNA 生物标志物研究揭示了存在前列腺癌风险的男性尿液中 IDO 基因表达的诊断潜力。
Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6. Inflammation-driven production and functions of PCa-TDFSs were tested “in vitro” by stimulating established cell lines (CA-HPV-10 and PC3) with IFN-γ or TNF-α. Expression of genes encoding IDO, IL-6, IFN-γ, TNF-α, and their receptors was investigated in tumor tissues of PCa patients undergoing radical prostatectomy, in comparison with benign prostatic hyperplasia (BPH) specimens. IFN-γ and TNF-α-treatment resulted in the induction of IDO and IL-6 gene expression and release in established cell lines, suggesting that the elicitation of PCa-TDSFs by these cytokines might contribute to progression of cancer into an untreatable phenotype. An analysis based on timing of biochemical recurrence revealed the prognostic value of IDO but not IL-6 gene expression in predicting recurrence-free survival in patients (RFS) with PCa. In addition, a urine-based mRNA biomarker study revealed the diagnostic potential of IDO gene expression in urines of men at risk of PCa development.