Fan Xin, Xie Fei, Zhang Lingling, Tong Chang, Zhang Zhiyuan
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
School of Stomatology, Nanchang University, Nanchang, China.
Front Mol Biosci. 2022 Aug 17;9:961450. doi: 10.3389/fmolb.2022.961450. eCollection 2022.
Factors such as variations in thyroid carcinoma (THCA) gene characteristics could influence the clinical outcome. Ferroptosis and immunity have been verified to play an essential role in various cancers, and could affect the cancer patients' prognosis. However, their relationship to the progression and prognosis of many types of THCA remains unclear. First, we extracted prognosis-related immune-related genes and ferroptosis-related genes from 2 databases for co-expression analysis to obtain prognosis-related differentially expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and screened BID and CDKN2A for building a prognostic model. Subsequently, multiple validation methods were used to test the model's performance and compare its performance with other 4 external models. Then, we explored the mechanism of immunity and ferroptosis in the occurrence, development and prognosis of THCA from the perspectives of anti-tumor immunity, CDKN2A-related competitive endogenous RNA regulatory, copy number variations and high frequency gene mutation. Finally, we evaluated this model's clinical practice value. BID and CDKN2A were identified as prognostic risk and protective factors, respectively. External data and qRT-PCR experiment also validated their differential expression. The model's excellent performance has been repeatedly verified and outperformed other models. Risk scores were significantly associated with most immune cells/functions. Risk score/2 PR-DE-IRFeGs expression was strongly associated with BRAF/NRAS/HRAS mutation. Single copy number deletion of CDKN2A is associated with upregulation of CDKN2A expression and worse prognosis. The predicted regulatory network consisting of CYTOR, hsa-miRNA-873-5p and CDKN2A was shown to significantly affect prognosis. The model and corresponding nomogram have been shown to have excellent clinical practice value. The model can effectively predict the THCA patients' prognosis and guide clinical treatment. Ferroptosis and immunity may be involved in the THCA's progression through antitumor immunity and BRAF/NRAS/HRAS mutation. CYTOR-hsa-miRNA-873-5p-CDKN2A regulatory networks and single copy number deletion of CDKN2A may also affect THCA' progression and prognosis.
甲状腺癌（THCA）基因特征的变化等因素可能会影响临床结果。铁死亡和免疫已被证实在各种癌症中起重要作用，并可能影响癌症患者的预后。然而，它们与多种类型THCA的进展和预后的关系仍不清楚。首先，我们从2个数据库中提取与预后相关的免疫相关基因和铁死亡相关基因进行共表达分析，以获得与预后相关的差异表达免疫相关铁死亡基因（PR-DE-IRFeGs），并筛选出BID和CDKN2A来构建预后模型。随后，使用多种验证方法来测试该模型的性能，并将其性能与其他4个外部模型进行比较。然后，我们从抗肿瘤免疫、CDKN2A相关的竞争性内源性RNA调控、拷贝数变异和高频基因突变的角度探讨了免疫和铁死亡在THCA发生、发展和预后中的机制。最后，我们评估了该模型的临床应用价值。BID和CDKN2A分别被确定为预后风险和保护因素。外部数据和qRT-PCR实验也验证了它们的差异表达。该模型的优异性能已得到反复验证，且优于其他模型。风险评分与大多数免疫细胞/功能显著相关。风险评分/2个PR-DE-IRFeGs表达与BRAF/NRAS/HRAS突变密切相关。CDKN2A的单拷贝数缺失与CDKN2A表达上调和预后较差有关。由CYTOR、hsa-miRNA-873-5p和CDKN2A组成的预测调控网络显示出显著影响预后。该模型和相应的列线图已显示出优异的临床应用价值。该模型可以有效地预测THCA患者的预后并指导临床治疗。铁死亡和免疫可能通过抗肿瘤免疫和BRAF/NRAS/HRAS突变参与THCA的进展。CYTOR-hsa-miRNA-873-5p-CDKN2A调控网络和CDKN2A的单拷贝数缺失也可能影响THCA的进展和预后。
