Zhao Yong-Xun, Yang Ze, Ma Li-Bin, Wang Fang, Wang Yong, Xiang Cheng
The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
The Pathology Department, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
Heliyon. 2023 Mar 17;9(3):e14714. doi: 10.1016/j.heliyon.2023.e14714. eCollection 2023 Mar.
To investigate the value of Hypoxia-inducible factor 1 A (HIF1A) in predicting lymph node metastasis (LNM) stage and clinical outcomes of papillary thyroid cancer (PTC) patients.
The HIF1A gene expression analysis in PTC was performed by bioinformatics approaches followed by evaluating its protein level using immunohistochemistry analysis. The role of HIF1A in predicting the LNM stage was evaluated by logistic regression analysis, nomogram construction, and receiver operating characteristic (ROC) analysis. We performed survival analyses to determine its prognostic value. Enrichment analysis was conducted, and immune cell infiltration and stromal content were evaluated to examine the underlying mechanism of HIF1A in PTC.
HIF1A transcription and protein levels were significantly high in PTC tissue (P < 0.05). Its overexpression predicted high LNM risk and unfavorable prognosis for PTC patients (P < 0.05). Cox regression analysis revealed HIF1A as an independent prognostic biomarker for the disease-free interval (DFI) (P < 0.01). In addition, HIF1A was positively related to tumor-suppressive immunity but was negatively correlated with anti-tumor immunity. HIF1A upregulation was also associated with increased stromal content.
HIF1A overexpression is an independent predictor for worse DFI in PTC. The HIF1A expression may affect the prognosis of PTC patients through immune- and stroma-related pathways. Our study provides new insight into the role of HIF1A in PTC biology and clinical management.
探讨缺氧诱导因子1A（HIF1A）在预测甲状腺乳头状癌（PTC）患者淋巴结转移（LNM）分期及临床结局中的价值。
采用生物信息学方法对PTC中的HIF1A基因表达进行分析，随后通过免疫组化分析评估其蛋白水平。通过逻辑回归分析、列线图构建和受试者工作特征（ROC）分析评估HIF1A在预测LNM分期中的作用。我们进行生存分析以确定其预后价值。进行富集分析，并评估免疫细胞浸润和基质含量，以研究HIF1A在PTC中的潜在机制。
PTC组织中HIF1A的转录和蛋白水平显著升高（P < 0.05）。其过表达预示PTC患者的LNM风险高且预后不良（P < 0.05）。Cox回归分析显示HIF1A是无病生存期（DFI）的独立预后生物标志物（P < 0.01）。此外，HIF1A与肿瘤抑制免疫呈正相关，但与抗肿瘤免疫呈负相关。HIF1A上调还与基质含量增加有关。
HIF1A过表达是PTC患者DFI较差的独立预测因子。HIF1A表达可能通过免疫和基质相关途径影响PTC患者的预后。我们的研究为HIF1A在PTC生物学和临床管理中的作用提供了新的见解。
