Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study)
Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study)
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DOI：
10.1016/j.trsl.2021.07.002
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发表时间：
2021-11-02
影响因子：
7.8
通讯作者：
Russo, Giorgio Ivan
中科院分区：
文献类型：
--
作者：
Broggi, Giuseppe;LO Giudice, Arturo;Russo, Giorgio Ivan
在过去的几年里，许多研究强调了糖尿病和高血糖可能与前列腺癌(PC)的发生和进展有关的假说。本研究旨在探讨雄激素受体(AR)、前列腺特异性膜抗原(PSMA)、Ki-67、胰岛素受体(IR)α和β、胰岛素生长因子-1(IGF-1)受体在PC患者组织中的表达及其与糖尿病的关系。我们回顾收集了2010-2020年间360例前列腺癌根治术或良性前列腺增生症(BPH)手术患者的数据。我们构建了用于免疫组织化学(IHC)分析的组织芯片。在最终队列(76例BPH和284例PC)中，57例(15.8%)合并糖尿病，17例(22.37%)合并BPH，40例(14.08%)合并PC(P=0.08)。PC组IR-a表达高于BPH组(95.96%vs4.04%；P0.01)。我们发现，AR与国际泌尿病理学会(ISUP)评分0.05的风险增加有关。最后，胰岛素样生长因子-1受体可预测糖尿病合并PC患者的ISUP4(OR：16.5；P=0.017)。在目前的研究中，我们强调了前列腺癌患者如何在组织中有不同的蛋白质表达。这种表达，特别是与IGF-1R相关的表达，与糖尿病患者更大的肿瘤侵袭性有关。我们认为这些结果归因于胰岛素信号的改变，从而决定了更大的有丝分裂活性，这可能会影响肿瘤的进展。(《翻译研究》2021；238：25-35)
In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR) a and beta, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. We constructed tissue microarray for immunohistochemistry (IHC) analysis. In the final cohort (76 BPH and 284 PC), 57 (15.8%) patients had diabetes, 17 (22.37%) in BPH and 40 (14.08%) in PC (P = 0.08). IR-a was more expressed in patients with PC compared to the BPH Group (95.96% vs 4.04%; P 0.01). We found that AR was associated with increased risk of International Society of Urological Pathology (ISUP) score 0.05). Finally, IGF-1 receptor was predictive of ISUP 4 (OR: 16.5; P =0.017) in patients with PC and diabetes. In the present study we highlighted how prostate cancer patients have a different protein expression in the tissue. This expression, and in particular that relating to IGF-1 R, is associated with greater tumor aggressiveness in those patients with diabetes. We suppose that these results are attributable to an alteration of the insulin signal which therefore determines a greater mitogenic activity that can influence tumor progression. (Translational Research 2021; 238:25-35)