Koren Ana, Rijavec Matija, Krumpestar Tomaž, Kern Izidor, Sadikov Aleksander, Čufer Tanja, Korošec Peter
University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia.
Faculty of Computer and Information Science, University of Ljubljana, 1000 Ljubljana, Slovenia.
Cancers (Basel). 2021 May 12;13(10):2309. doi: 10.3390/cancers13102309.
Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate , and mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS).
Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. , and mRNA expressions were measured using RT-qPCR.
The and mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both < 0.0001). and expression in tumours was positively correlated ( = 0.82; < 0.0001) and correlated well with HIF pathway downstream genes , and . Decreased and were associated with larger tumour size, higher tumour stage ( only) and squamous cell carcinoma. Patients with low and patients with low expression had shorter OS than patients with high ( = 0.02) and expression ( = 0.01). showed borderline independent prognostic values in multivariate analysis ( = 0.06). In contrast, we found no associations between expression and any of the observed parameters.
Our results show that reduced expression of and is associated with the development and progression of NSCLC. could be further assessed as a prognostic marker in NSCLC.
缺氧与包括肺癌在内的多种癌症类型的不良预后相关。脯氨酰羟化酶结构域蛋白（PHD）在细胞氧感应中起作用，对缺氧诱导因子（HIF）通路起负调节作用。我们的研究目的是评估非小细胞肺癌（NSCLC）患者原发性肿瘤和正常肺组织中 、 和 mRNA 的表达水平，并将其与 HIF 信号的选定调节因子、临床病理特征和总生存期（OS）相关联。
从 60 例行根治性手术的 NSCLC 患者中获取肿瘤组织样本。60 例中有 22 例获得了形态学上匹配的正常肺组织。使用 RT-qPCR 测量 、 和 mRNA 的表达。
与正常肺组织相比，原发性肿瘤中的 和 mRNA 水平显著降低（均 < 0.0001）。肿瘤中的 和 表达呈正相关（ = 0.82； < 0.0001），并与 HIF 通路下游基因 、 和 密切相关。 和 的降低与肿瘤体积较大、肿瘤分期较高（仅 ）和鳞状细胞癌相关。 和 表达低的患者的 OS 比 和 表达高的患者短（ = 0.02）和 表达高的患者短（ = 0.01）。在多变量分析中， 显示出临界独立预后价值（ = 0.06）。相比之下，我们发现 表达与任何观察到的参数之间均无关联。
我们的结果表明， 和 表达降低与 NSCLC 的发生和进展相关。 可作为 NSCLC 的预后标志物进一步评估。
