Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Front Immunol. 2023 Oct 3;14:1187160. doi: 10.3389/fimmu.2023.1187160. eCollection 2023.
The incidence of thyroid carcinoma (THCA), the most common endocrine tumor, is continuously increasing worldwide. Although the overall prognosis of THCA is good, patients with distant metastases exhibit a mortality rate of 5-20%.
To improve the diagnosis and overall prognosis of patients with thyroid cancer, we screened specific candidate neoantigen genes in early- and late-stage THCA by analyzing the transcriptome and somatic cell mutations in this study.
The top five early-stage neoantigen-related genes (NRGs) were G protein-coupled receptor 4 [], chondroitin sulfate proteoglycan 4 [], teneurin transmembrane protein 1 [], protein S 1 [], and thymidine kinase 1 [], whereas the top five late-stage NRGs were cadherin 6 [], semaphorin 6B [], dysferlin [], xenotropic and polytropic retrovirus receptor 1 [], and ABR activator of RhoGEF and GTPase []. Subsequently, we used machine learning models to verify their ability to screen NRGs and analyze the correlations among NRGs, immune cell types, and immune checkpoint regulators. The use of candidate antigen genes resulted in a better diagnostic model (the area under the curve [AUC] value of the early-stage group [0.979] was higher than that of the late-stage group [0.959]). Then, a prognostic model was constructed to predict NRG survival, and the 1-, 3- and 5-year AUC values were 0.83, 0.87, and 0.86, respectively, which were closely related to different immune cell types. Comparison of the expression trends and mutation frequencies of NRGs in multiple tumors revealed their potential for the development of broad spectrum therapeutic drugs.
In conclusion, the candidate NRGs identified in this study could potentially be used as therapeutic targets and diagnostic biomarkers for the development of novel broad spectrum therapeutic agents.
甲状腺癌（THCA）是最常见的内分泌肿瘤，其发病率在全球范围内持续上升。尽管 THCA 的总体预后良好，但远处转移的患者死亡率为 5-20%。
为了提高甲状腺癌患者的诊断和总体预后，我们通过分析本研究中转录组和体细胞突变，筛选出早期和晚期 THCA 特异性候选新抗原基因。
前 5 个早期新抗原相关基因（NRG）分别为 G 蛋白偶联受体 4 [GPR4]、软骨素硫酸蛋白聚糖 4 [CSPG4]、腱蛋白跨膜蛋白 1 [TENM1]、蛋白 S 1 [PROS1]和胸苷激酶 1 [TK1]，而前 5 个晚期 NRG 分别为钙粘蛋白 6 [CDH6]、神经递质 Semaphorin 6B [SEMA6B]、肌营养不良蛋白 [DYSF]、异嗜性和多瘤病毒受体 1 [XPR1]和 RhoGEF 和 GTPase 的激活剂 ABR [ABR]。随后，我们使用机器学习模型验证了它们筛选 NRG 的能力，并分析了 NRG 与免疫细胞类型和免疫检查点调节剂之间的相关性。使用候选抗原基因可获得更好的诊断模型（早期组的曲线下面积 [AUC] 值[0.979]高于晚期组[0.959]）。然后，构建了一个预测 NRG 生存的预后模型，其 1、3 和 5 年 AUC 值分别为 0.83、0.87 和 0.86，与不同的免疫细胞类型密切相关。比较多个肿瘤中 NRG 的表达趋势和突变频率，揭示了其开发广谱治疗药物的潜力。
综上所述，本研究中鉴定的候选 NRG 可能作为新型广谱治疗药物的治疗靶点和诊断生物标志物。
