Pol Arch Intern Med. 2017 Nov 30;127(11):758-764. doi: 10.20452/pamw.4115. Epub 2017 Sep 30.
INTRODUCTION Signal transducer and activator of transcription (STAT) proteins are critically involved in tumorigenesis in various cancers, including lung cancer. OBJECTIVES The aim of the study was to analyze the immunoexpression levels of 3 STAT proteins: STAT3, STAT5, and STAT6 in their phosphorylated forms (pSTATs), STAT inhibitors PIAS3 and SOCS3, and additionally cyclooxygenase 2 (COX‑2), as potential diagnostic and prognostic markers in lung cancer. PATIENTS AND METHODS The study included 71 patients diagnosed with non- small-cell lung cancer (NSCLC). The immunoexpression levels of the proteins were assessed in lung tissue samples, using an enzyme‑linked immunosorbent assay. Tumors were staged using the postoperative TNM classification. RESULTS All studied STATs were overexpressed in 54% to 55% of NSCLC specimens. Significantly higher STAT3 and STAT6 immunoexpression levels were observed in squamous cell carcinoma. Significant differences between NSCLC samples and controls were found for STAT5. Significantly higher STAT5 levels were observed in pT2 tumors. The COX‑2 overexpression was observed in 55% of NSCLC specimens and was significantly higher in T2 tumors. STAT inhibitors were underexpressed in 56% to 58% of NSCLC specimens. The PIAS3 immunoexpression was significantly lower in non-squamous cell carcinoma. The SOCS3 level was significantly lower in smaller tumors (pT1). Negative correlations between STAT5 and PIAS3 levels, as well as between STAT6 and SOCS levels, and a positive correlation between STAT5 and COX-2 levels were observed. CONCLUSIONS The deregulated expression of the studied pSTATs and their inhibitors may be involved in the development and progression of lung cancer. The observed differences between the histotypes suggest the potential usefulness of STAT proteins as diagnostic markers. Our results may contribute to the search for targets in lung cancer therapy.
信号转导子和转录激活子（STAT）蛋白在各种癌症的肿瘤发生中起着至关重要的作用，包括肺癌。目的：本研究旨在分析 3 种磷酸化形式（pSTATs）的 STAT 蛋白（STAT3、STAT5 和 STAT6）、STAT 抑制剂 PIAS3 和 SOCS3 以及环氧化酶 2（COX-2）在非小细胞肺癌（NSCLC）中的免疫表达水平，作为潜在的诊断和预后标志物。患者和方法：本研究纳入了 71 例诊断为非小细胞肺癌（NSCLC）的患者。使用酶联免疫吸附试验（ELISA）评估了肺组织样本中蛋白质的免疫表达水平。肿瘤采用术后 TNM 分期进行分期。结果：所有研究的 STAT 在 54%至 55%的 NSCLC 标本中过表达。鳞状细胞癌中观察到 STAT3 和 STAT6 的免疫表达水平显著升高。在 NSCLC 样本和对照之间观察到 STAT5 存在显著差异。pT2 肿瘤中观察到显著较高的 STAT5 水平。55%的 NSCLC 标本中 COX-2 过表达，在 T2 肿瘤中过表达更为显著。STAT 抑制剂在 56%至 58%的 NSCLC 标本中表达不足。非鳞状细胞癌中 PIAS3 的免疫表达明显降低。较小肿瘤（pT1）的 SOCS3 水平明显降低。观察到 STAT5 和 PIAS3 水平之间以及 STAT6 和 SOCS 水平之间存在负相关，以及 STAT5 和 COX-2 水平之间存在正相关。结论：研究的 pSTAT 和其抑制剂的失调表达可能参与了肺癌的发生和发展。观察到的组织型之间的差异表明 STAT 蛋白作为诊断标志物具有潜在的用途。我们的研究结果可能有助于寻找肺癌治疗的靶点。
