Zhang Guoliang, Li Bing, Lin Yuanmei
Department of Thyroid Surgery, Affiliated Hospital of Putian University, Putian, China.
Department of Medical Oncology, Affiliated Hospital of Putian University, Putian, China.
Front Oncol. 2022 Jan 31;11:614955. doi: 10.3389/fonc.2021.614955. eCollection 2021.
To investigate the expression of ITGA3 and its association with clinical outcomes in papillary thyroid carcinoma (PTC).
The expression level, association with clinicopathologic characteristics, co-expressed genes, signaling pathways of ITGA3 in thyroid cancer were comprehensively analyzed using bioinformatics analysis through multiple public gene databases. PTC specimens and cell lines were used to verify the results of bioinformatics analysis.
Data mining based on the Oncomine database revealed that ITGA3 expression in classical PTC and tall cell variant PTC was much higher than that in normal thyroid tissue except the follicular variant PTC. Analysis based on The Cancer Genome Atlas (TCGA) database showed that the expression of ITGA3 varies greatly in pathological stages, pathological types, tumor invasion stages, and lymph node metastasis stages of thyroid carcinoma. High expression level of ITGA3 was correlated with tumor regional invasion and lymph node metastasis. Multivariate analysis using logistic regression model showed that high expression of ITGA3 was a risk factor that associated with PTC recurrence and lymph node metastasis. Survival analysis showed that patients with high expression of ITGA3 in PTC had a poorer relapse-free survival (RFS) than patients with low expression of ITGA3 (P < 0.05). Immunohistochemistry experiments showed that the expression of ITGA3 in recurrent thyroid cancer tissues was stronger than that in no-recurrent thyroid cancer tissues (P < 0.05). Knockdown of ITGA3 by sh-RNA in PTC cell lines suppresses cell viability and invasive and migrating capacity.
ITGA3 is overexpressed in PTC, especially in those with higher tumor invasion grades and lymph node metastasis, and was associated with recurrence and poor RFS of PTC. High expression of ITGA3 may have the potential role of predicting PTC recurrence and lymph node metastasis.
探讨整合素α3（ITGA3）在甲状腺乳头状癌（PTC）中的表达及其与临床结局的关系。
通过多个公共基因数据库，利用生物信息学分析全面分析ITGA3在甲状腺癌中的表达水平、与临床病理特征的相关性、共表达基因及信号通路。采用PTC标本和细胞系验证生物信息学分析结果。
基于Oncomine数据库的数据挖掘显示，除滤泡状变异型PTC外，经典型PTC和高细胞变异型PTC中ITGA3的表达远高于正常甲状腺组织。基于癌症基因组图谱（TCGA）数据库的分析表明，ITGA3的表达在甲状腺癌的病理分期、病理类型、肿瘤侵袭阶段和淋巴结转移阶段有很大差异。ITGA3高表达与肿瘤局部侵袭和淋巴结转移相关。使用逻辑回归模型的多因素分析显示，ITGA3高表达是与PTC复发和淋巴结转移相关的危险因素。生存分析表明，PTC中ITGA3高表达的患者无复发生存期（RFS）较ITGA3低表达的患者差（P<0.05）。免疫组织化学实验表明，复发性甲状腺癌组织中ITGA3的表达强于非复发性甲状腺癌组织（P<0.05）。在PTC细胞系中用sh-RNA敲低ITGA3可抑制细胞活力以及侵袭和迁移能力。
ITGA3在PTC中过表达，尤其是在肿瘤侵袭分级和淋巴结转移较高的患者中，且与PTC的复发和不良RFS相关。ITGA3高表达可能具有预测PTC复发和淋巴结转移的潜在作用。
