Li Jiali, Lan Lili, Xu Yuru, Liu Shenghui, Liu Meng, Hu Guobin, Wu Ganxun, Zhao Yan, Shi Jian, Wang Jingtian, Sun Yixin, Wang Zhanlong, Zhao Ruili
Research Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Department of Otolaryngology Head and Neck Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Oncol Lett. 2023 Jun 2;26(1):310. doi: 10.3892/ol.2023.13896. eCollection 2023 Jul.
The aim of the present study was to evaluate the expression of TRAF2- and NCK-interacting kinase (TNIK) and the levels of the active form of TNIK, phosphorylated (p)-TNIK, in papillary thyroid carcinoma (PTC), and to identify and compare the levels of TNIK and p-TNIK among PTC, benign thyroid tumors and normal tissues. The levels of TNIK and p-TNIK were examined by reverse transcription-quantitative (RT-q)PCR and immunohistochemical analysis (IHC) in PTC, benign thyroid tumors and normal tissues, and their association with clinicopathological features was evaluated. First, analysis of the Gene Expression Profiling Interactive Analysis and The Cancer Genome Atlas datasets suggested that the mRNA expression of TNIK was markedly increased in PTC tissues compared with that in normal tissues. RT-qPCR analyses then indicated that the relative mRNA expression of TNIK in PTC tissues was 4.47±6.16, which was significantly higher than that in adjacent tissues 2.57±5.83. The IHC results suggested that the levels of TNIK and p-TNIK in PTC tissues were markedly elevated compared with those in benign thyroid tumors and normal tissues. The levels of p-TNIK in patients with PTC were significantly associated with extrathyroidal extension (χ=4.199, P=0.040). Positive staining for TNIK was observed in 187 out of 202 (92.6%) cases in the cytoplasm, nucleus or cytomembrane of PTC cells. Among the 187 positive cases, cytoplasm expression was identified in 162 cases (86.6%), nuclear expression in 17 cases (9.1%) and cytomembrane expression in 8 cases (4.3%). Positive staining for p-TNIK was observed in 179 out of 202 (88.6%) cases in the nuclei, cytoplasm or cytomembrane of PTC cells. In the 179 p-TNIK-positive cases, localization in the nuclei plus cytoplasm was identified in 142 cases (79.3%), nuclear localization in 9 cases (5.0%), presence in the cytoplasm in 21 cases (11.7%) and cytomembrane localization in 7 cases (3.9%). Both TNIK and p-TNIK were upregulated in PTC tissues and p-TNIK was significantly associated with extrathyroidal extension. It may act as a crucial oncogene to participate in PTC carcinogenesis and progression.
本研究旨在评估甲状腺乳头状癌（PTC）中TRAF2与NCK相互作用激酶（TNIK）的表达以及TNIK活性形式（磷酸化TNIK，p-TNIK）的水平，并鉴定和比较PTC、甲状腺良性肿瘤及正常组织中TNIK和p-TNIK的水平。通过逆转录定量（RT-q）PCR和免疫组织化学分析（IHC）检测PTC、甲状腺良性肿瘤及正常组织中TNIK和p-TNIK的水平，并评估它们与临床病理特征的相关性。首先，对基因表达谱交互分析和癌症基因组图谱数据集的分析表明，与正常组织相比，PTC组织中TNIK的mRNA表达显著增加。随后的RT-qPCR分析表明，PTC组织中TNIK的相对mRNA表达为4.47±6.16，显著高于相邻组织的2.57±5.83。IHC结果表明，与甲状腺良性肿瘤和正常组织相比，PTC组织中TNIK和p-TNIK的水平显著升高。PTC患者中p-TNIK的水平与甲状腺外侵犯显著相关（χ=4.199，P=0.040）。在202例PTC细胞的细胞质、细胞核或细胞膜中，有187例（92.6%）观察到TNIK阳性染色。在187例阳性病例中，162例（86.6%）为细胞质表达，17例（9.1%）为细胞核表达，8例（4.3%）为细胞膜表达。在202例PTC细胞的细胞核、细胞质或细胞膜中，有179例（88.6%）观察到p-TNIK阳性染色。在179例p-TNIK阳性病例中，142例（79.3%）为细胞核加细胞质定位，9例（5.0%）为细胞核定位，21例（11.7%）为细胞质定位，7例（3.9%）为细胞膜定位。TNIK和p-TNIK在PTC组织中均上调，且p-TNIK与甲状腺外侵犯显著相关。它可能作为一种关键的癌基因参与PTC的发生和发展。
