Department of Otorhinolaryngology, Head and Neck Surgery, the Second Hospital, Tianjin Medical University, Tianjin, China.
Department of Pharmaceutics, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Endocrine. 2022 Dec;78(3):491-506. doi: 10.1007/s12020-022-03175-9. Epub 2022 Sep 7.
The aim of this study was to construct a collagen-related prognostic model for thyroid cancer and to investigate prognostic value of collagen family genes for thyroid cancer.
A LASSO Cox regression model for thyroid cancer was developed based on the expression profiles of collagen-related genes. Kaplan-Meier survival analysis was performed for high and low risk groups. The ROC method was used to assess its predictive performance. Predictive independence was verified by multivariate Cox regression analysis. The relationship between this feature and immune cell infiltration was analyzed by tumor microenvironment. COL18A1 was validated by immunohistochemistry and RT-PCR in thyroid cancer tissues. The effect of COL18A1 on cell proliferation, migration and invasion ability of tumor cells were further valuated by CCK-8 assay and transwell assay. The effect of COL18A1 on the immune escape ability of tumor cells was further valuated by cytotoxicity assays.
A model including 4 collagen family genes was developed to predict thyroid cancer prognosis. Patients with high-risk score had a poorer prognosis than those with low-risk scores for 1-, 2-, 3-, and 5- year survival. The model independently predicted prognosis after adjusting for other prognostic factors. A nomogram combining risk score and age was constructed with high sensitivity and specificity. This feature was significantly associated with immune cell infiltration. COL18A1 was aberrantly over-expressed in thyroid cancer compared with control tissues and significantly increased proliferative capacity, migration capacity, invasion capacity, and immune escape ability of tumor cells.
Our findings establish a signature associated with collagen family genes that can be a promising tool to predict the prognosis of thyroid cancer. High COL18A1 expression significantly correlates with the poor prognosis of patients and enhances the immune escape ability of tumor cells.
本研究旨在构建甲状腺癌胶原相关预后模型，并探讨胶原家族基因对甲状腺癌的预后价值。
基于胶原相关基因的表达谱，建立了甲状腺癌的 LASSO Cox 回归模型。对高低风险组进行 Kaplan-Meier 生存分析。采用 ROC 方法评估其预测性能。通过多变量 Cox 回归分析验证预测独立性。通过肿瘤微环境分析该特征与免疫细胞浸润的关系。采用免疫组织化学和 RT-PCR 验证 COL18A1 在甲状腺癌组织中的表达。通过 CCK-8 检测和 Transwell 检测进一步评估 COL18A1 对肿瘤细胞增殖、迁移和侵袭能力的影响。通过细胞毒性测定进一步评估 COL18A1 对肿瘤细胞免疫逃逸能力的影响。
建立了一个包含 4 个胶原家族基因的模型，用于预测甲状腺癌的预后。高风险评分的患者在 1、2、3 和 5 年的生存率均低于低风险评分的患者。该模型在调整其他预后因素后可独立预测预后。构建了一个结合风险评分和年龄的列线图，具有较高的敏感性和特异性。该特征与免疫细胞浸润显著相关。与对照组织相比，COL18A1 在甲状腺癌中过度表达，显著增加了肿瘤细胞的增殖能力、迁移能力、侵袭能力和免疫逃逸能力。
我们的研究结果建立了一个与胶原家族基因相关的特征，可作为预测甲状腺癌预后的有前途的工具。COL18A1 高表达与患者预后不良显著相关，并增强了肿瘤细胞的免疫逃逸能力。
