目的:本研究旨在构建与胶原相关的甲状腺癌预后模型,并探讨胶原家族基因对甲状腺癌预后的预测价值。
方法:基于胶原相关基因的表达谱,建立了甲状腺癌的LASSOCox回归模型。对高危和低危组进行Kaplan-Meier生存分析。ROC方法用于评估其预测性能。多因素Cox回归分析验证了预测独立性。通过肿瘤微环境分析了该特征与免疫细胞浸润之间的关系。通过免疫组织化学和RT-PCR验证了COL18A1在甲状腺癌组织中的表达。COL18A1对细胞增殖的影响,通过CCK-8法和transwell法进一步评价肿瘤细胞的迁移和侵袭能力。通过细胞毒性试验进一步评价了COL18A1对肿瘤细胞免疫逃逸能力的影响。
结果:建立了包括4个胶原家族基因的模型来预测甲状腺癌的预后。高风险评分的患者的预后比具有低风险评分的患者差1-,2-,3-,5年生存率。该模型在调整其他预后因素后独立预测预后。结合风险评分和年龄的列线图以高灵敏度和特异性构建。该特征与免疫细胞浸润显著相关。与对照组织相比,COL18A1在甲状腺癌中异常过表达,并且增殖能力显着增加,迁移能力,入侵能力,和肿瘤细胞的免疫逃逸能力。
结论:我们的研究结果建立了与胶原家族基因相关的特征,可以作为预测甲状腺癌预后的有前景的工具。COL18A1的高表达与患者的不良预后密切相关,并增强肿瘤细胞的免疫逃逸能力。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.