Objective

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.

Materials and methods

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.

Results

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.

Conclusions

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.

中文翻译：

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HIF1A 过表达预示着甲状腺乳头状癌的高淋巴结转移风险和预后不良

客观的

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）分期和临床结局中的价值。

材料和方法

PTC 中的 HIF1A 基因表达分析是通过生物信息学方法进行的，然后使用免疫组织化学分析评估其蛋白质水平。HIF1A 在预测 LNM 分期中的作用通过逻辑回归分析、列线图构建和接受者操作特征 (ROC) 分析进行评估。我们进行了生存分析以确定其预后价值。进行了富集分析，并评估了免疫细胞浸润和基质含量，以检查 PTC 中 HIF1A 的潜在机制。

结果

HIF1A 转录和蛋白水平在 PTC 组织中显着升高 (P < 0.05)。其过表达预示着 PTC 患者的高 LNM 风险和不良预后（P < 0.05）。Cox 回归分析显示 HIF1A 是无病间期 (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，与抗肿瘤免疫呈负相关。HIF1A 上调也与基质含量增加有关。

结论

HIF1A 过表达是 PTC 中较差 DFI 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。