Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Medicine (Baltimore). 2023 Mar 10;102(10):e33232. doi: 10.1097/MD.0000000000033232.
hypoxia inducible factor-1α (HIF-1α) and pyruvate kinase M2 (PKM2) are 2 key metabolic regulatory proteins, they could engage in a positive feedback loop and drive cancer growth by enhancing glycolysis. This study aimed to investigate the expression of HIF-1α and PKM2 in papillary thyroid carcinoma (PTC) and its correlation with the patients clinicopathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 60 patients were collected. The expression levels of HIF-1α and PKM2 in PTC tissues were examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between HIF-1α and PKM2 expressions and the clinical pathological features of PTC. The results showed that the positive expressions of HIF-1α, PKM2, and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all significantly higher in PTC than those in normal thyroid follicular epithelium, and a positive correlation was found between HIF-1α and PKM2 in PTC. Further analysis showed that in PTC, the positive expression of HIF-1α and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were significantly associated with bigger tumor size, moreover, the positive expressions of HIF-1α, PKM2 and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all correlated with capsular invasion and lymph node metastasis, while they were all not correlated with gender, sex and multicentricity of tumor. This study identified HIF-1a/PKM2 axis as potential molecular marker for predicting the invasion and progression of papillary thyroid carcinoma.
缺氧诱导因子-1α(HIF-1α)和丙酮酸激酶 M2(PKM2)是 2 种关键的代谢调节蛋白,它们可以通过增强糖酵解作用,形成正反馈回路并促进肿瘤生长。本研究旨在探讨 HIF-1α和 PKM2 在甲状腺乳头状癌(PTC)中的表达及其与患者临床病理特征、肿瘤侵袭和转移的相关性。收集 60 例手术切除的 PTC 标本,采用免疫组化染色法检测 PTC 组织中 HIF-1α和 PKM2 的表达水平。收集所有患者的完整临床记录,分析 HIF-1α和 PKM2 表达与 PTC 临床病理特征的相关性。结果显示,与正常甲状腺滤泡上皮相比,HIF-1α、PKM2 及 HIF-1α/PKM2 轴(HIF-1α+/PKM2+)在 PTC 中的阳性表达均显著升高,且在 PTC 中 HIF-1α 与 PKM2 呈正相关。进一步分析表明,在 PTC 中,HIF-1α 和 HIF-1α/PKM2 轴(HIF-1α+/PKM2+)的阳性表达与肿瘤体积较大显著相关,此外,HIF-1α、PKM2 和 HIF-1α/PKM2 轴(HIF-1α+/PKM2+)的阳性表达均与包膜侵犯和淋巴结转移相关,而与性别、年龄和肿瘤多灶性均无关。本研究发现 HIF-1α/PKM2 轴可能是预测甲状腺乳头状癌侵袭和进展的潜在分子标志物。