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| YTHDF1 COL17A1及STING与乳腺癌脊柱转移患者临床病理特征和生存预后的关系 |
| Relationship between YTHDF1, COL17A1 and STING and clinicopathological characteristics and survival prognosis of patients with spinal metastases from breast cancer |
| 投稿时间：2025-07-29 |
| DOI：10.3969/j.issn.1000-0399.2026.03.010 |
| 中文关键词: 乳腺癌 脊柱转移 N6-甲基腺苷RNA结合蛋白1 胶原蛋白17α链 干扰素基因刺激因子 临床病理特征 预后 |
| 英文关键词: Breast cancer Spinal metastasis N6-methyladenosine RNA-binding protein 1 Collagen 17α chain Stimulator of interferon genes Clinicopathological features Prognosis |
| 基金项目:东莞市社会发展科技项目(编号:20231800905042,20231800935892) |
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| 摘要点击次数: 529 |
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| 中文摘要: |
| 目的 探讨N6-甲基腺苷RNA结合蛋白1（YTHDF1）、胶原蛋白17α链（COL17A1）及干扰素基因刺激因子（STING）与乳腺癌脊柱转移患者临床病理特征和生存预后的关系。方法 收集2022年1月至2024年1月南方医科大学第十附属医院（东莞市人民医院）收治的100例乳腺癌脊柱转移患者的脊柱转移组织，另收集同期收治的50例无转移乳腺癌患者的癌组织及其癌旁组织，检测各组织中YTHDF1、COL17A1、STING信使RNA（mRNA）及其蛋白表达情况，采用Pearson相关性分析乳腺癌脊柱转移组织中YTHDF1、COL17A1、STING mRNA表达水平的相关性。对乳腺癌脊柱转移患者进行随访，分析各指标对乳腺癌脊柱转移患者生存预后的影响，并绘制受试者工作特征（ROC）曲线评估各指标对乳腺癌脊柱转移患者生存预后的预测价值。结果 乳腺癌脊柱转移组织中YTHDF1 mRNA及其蛋白阳性表达率高于无转移癌组织及癌旁组织（P<0.05）,COL17A1 mRNA、STING mRNA及其蛋白阳性表达率低于无转移癌组织及癌旁组织（P<0.05）。乳腺癌脊柱转移组织中YTHDF1 mRNA水平与COL17A1 mRNA、STING mRNA水平呈负相关（r=-0.360、-0.370,P<0.001）;COL17A1 mRNA水平与STING mRNA水平呈正相关性（r=0.220、P=0.030,P<0.05）。YTHDF1、COL17A1、STING蛋白阳性表达与乳腺癌脊柱转移患者伴随其他部位转移有关（P<0.05）。随访结果显示，100例乳腺癌脊柱转移患者总生存率63.00%（63/100）,YTHDF1蛋白阳性表达患者的生存率低于阴性表达患者（χ2=6.966,P=0.008）;COL17A1、STING蛋白阳性表达患者的生存率高于阴性表达患者（χ2=12.745、7.815,P均<0.05）。伴随其他部位转移（HR=1.981,P=0.027,95%CI:1.240～3.765）、YTHDF1蛋白阳性（HR=2.477,P=0.018,95%CI:1.311～3.729）是影响乳腺癌脊柱转移患者生存预后的独立危险因素，COL17A1（HR=0.824,P=0.022,95%CI:0.337～0.913）、STING（HR=0.817,P=0.027,95%CI:0.305～0.895）蛋白阳性是保护性因素。YTHDF1、COL17A1、STING mRNA表达水平单独预测乳腺癌脊柱转移患者死亡的AUC分别为0.811、0.789、0.783,3项联合预测的曲线下面积（AUC）为0.950，大于各指标单独预测的AUC（Z=3.365、3.388、3.425,P均<0.05）。结论 YTHDF1在乳腺癌脊柱转移组织中高表达，COL17A1、STING低表达，3者均与肿瘤转移、及患者预后密切相关。 |
| 英文摘要: |
| Objective To investigate the relationship between N6-methyladenosine RNA-binding protein 1（YTHDF1）, collagen 17α chain（COL17A1） and interferon gene stimulating factor（STING） and the clinicopathological characteristics and survival prognosis of patients with spinal metastases from breast cancer. Methods Spinal metastatic tissue samples were collected from 100 patients with breast cancer spinal metastases at the The First Affiliated Hospital of Southern Medical University（Dongguan People's Hospital） between January 2022 and January 2024. Additionally, cancer tissue and paired adjacent tissue samples were collected from 50 non-metastatic breast cancer patients admitted during the same period. The mRNA and protein expression levels of YTHDF1, COL17A1, and STING were detected in all tissues. Pearson correlation analysis was used to analyze the correlations among the mRNA expression levels of YTHDF1, COL17A1, and STING in the spinal metastatic tissues. Patients with breast cancer spinal metastases were followed up to analyze the impact of each indicator on their survival prognosis. Receiver operating characteristic（ROC） curves were plotted to evaluate the predictive value of each indicator for the survival prognosis of these patients. Results The positive expression rate of YTHDF1 mRNA and its protein in spinal metastatic tissues of breast cancer was higher than that in non-metastatic cancer tissues and paracancerous tissues（P < 0.05）, and the positive expression rate of COL17A1 mRNA, STING mRNA and its protein was lower than that in non-metastatic cancer tissues and paracancerous tissues（P < 0.05）. In the spinal metastatic tissues of breast cancer, the levels of YTHDF1 mRNA were negatively correlated with those of COL17A1 mRNA and STING mRNA（r=-0.360,-0.370, all P < 0.001）; the levels of COL17A1 mRNA were positively correlated with those of STING mRNA（r=0.220, P=0.030）. Positive expression of YTHDF1, COL17A1, and STING proteins was associated with concomitant metastasis to other sites in patients with spinal metastases from breast cancer（P < 0.05）. The follow-up showed that the overall survival rate of 100 patients with breast cancer spinal metastasis was 63.00%（63/100）, and the survival rate of patients with positive expression of YTHDF1 protein was lower than that of patients with negative expression（χ2=6.966, P=0.008）. The survival rate of patients with positive expression of COL17A1 and STING proteins was higher than that of patients with negative expression（χ2=12.745, 7.815; all P < 0.01）. The presence of metastasis to other sites（HR=1.981, P=0.027, 95% CI: 1.240～3.765） and positive YTHDF1 protein expression（HR=2.477, P=0.018, 95% CI: 1.311～3.729） were independent risk factors affecting the survival prognosis of patients with breast cancer spinal metastases. Positive COL17A1（HR=0.824, P=0.022, 95% CI: 0.337～0.913） and STING（HR=0.817, P=0.027, 95% CI: 0.305～0.895） protein expression were protective factors. The AUCs of YTHDF1, COL17A1, and STING mRNA expression levels alone for predicting death in patients with spinal metastases from breast cancer were 0.811, 0.789, 0.783, respectively, and the AUC predicted by the combination of the three items was 0.950, which was greater than that predicted by each index alone（Z=3.365, 3.388, 3.425, all P<0.05）. Conclusion YTHDF1 is highly expressed in breast cancer spinal metastasis tissues, COL17A1 and STING are lowly expressed, and all the three are closely related to tumour metastasis and patient prognosis. |
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