Pavlakis Dimitrios, Kampantais Spyridon, Gkagkalidis Konstantinos, Gourvas Victoras, Memmos Dimitrios, Tsionga Aikaterini, Dimitriadis Georgios, Vakalopoulos Ioannis
1st Urologic Department, Gennimatas General Hospital, 37782Aristotle University of Thessaloniki, Thessaloniki, Greece.
Saint Luke's Private Hospital of Thessaloniki, Thessaloniki, Greece.
Technol Cancer Res Treat. 2021 Jan-Dec;20:1533033821990010. doi: 10.1177/1533033821990010.
One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer.
The immunohistochemical expression of HIF-1a, HIF-2a and their regulators, prolyl hydroxylase domain (PHD)1, PHD2 and PHD3 and factor inhibiting HIF (FIH), was assessed on a tissue microarray. This was constructed from radical prostatectomy specimens, involving both tumor and corresponding adjacent non-tumoral prostate tissues from 50 patients with localized or locally advanced prostate cancer.
In comparison with non-tumoral adjacent tissue, HIF-1a exhibited an equal or lower expression in 86% of the specimens (P = 0.017), while HIF-2a was overexpressed in 52% (P = 0.032) of the cases. HIF-1a protein expression was correlated with HIF-2a (P < 0.001), FIH (P = 0.004), PHD1 (P < 0.001), PHD2 (P < 0.001) and PHD3 (P = 0.035). HIF-2a expression was positively correlated with Gleason score (P = 0.017) and International Society of Urological Pathologists (ISUP) grade group (P = 0.022).
The findings of the present study suggest a key role for HIF-2a in prostate cancer, as HIF-2a expression was found to be correlated with Gleason score and ISUP grade of the patients. However, further studies are required to validate these results and investigate the potential value of HIF-2a as a therapeutic target in prostate cancer.
肿瘤微环境中对缺氧反应的主要因素之一是缺氧诱导因子（HIF）途径。尽管其在其他实体瘤，尤其是肾细胞癌中的作用已得到充分阐明，但在前列腺癌中仍不清楚。本研究的目的是调查该途径中主要蛋白的表达，并确定结果与前列腺癌患者临床病理结果的相关性。
在组织芯片上评估HIF-1α、HIF-2α及其调节因子脯氨酰羟化酶结构域（PHD）1、PHD2和PHD3以及抑制HIF（FIH）的免疫组化表达。该组织芯片由前列腺癌根治术标本构建而成，涉及50例局限性或局部晚期前列腺癌患者的肿瘤组织及相应的相邻非肿瘤性前列腺组织。
与非肿瘤性相邻组织相比，86%的标本中HIF-1α表达相同或更低（P = 0.017），而52%的病例中HIF-2α过表达（P = 0.032）。HIF-1α蛋白表达与HIF-2α（P < 0.001）、FIH（P = 0.004）、PHD1（P < 0.001）、PHD2（P < 0.001）和PHD3（P = 0.035）相关。HIF-2α表达与Gleason评分（P = 0.017）和国际泌尿病理学家协会（ISUP）分级组（P = 0.022）呈正相关。
本研究结果表明HIF-2α在前列腺癌中起关键作用，因为发现HIF-2α表达与患者的Gleason评分和ISUP分级相关。然而，需要进一步研究来验证这些结果，并研究HIF-2α作为前列腺癌治疗靶点的潜在价值。
