非小细胞肺癌患者血清miR-550a-5p水平与脊柱转移的关系

Analysis of the correlation between serum miR-550a-5p levels and spinal metastasis in patients with non-small cell lung cancer

中文关键词:  非小细胞肺癌  脊柱转移  骨代谢相关肿瘤标志物  联合诊断

英文关键词:Non-small cell lung cancer  Spinal metastasis  Bone metabolism-related tumor marker  Combined diagnosis

中文摘要:

  【摘要】 目的：探讨非小细胞肺癌（non-small cell lung cancer，NSCLC）患者血清miR-550a-5p水平与脊柱转移的关系。方法：回顾性分析2021年5月~2023年5月在承德医学院附属医院接受治疗的175例NSCLC患者的临床资料。根据全身骨显像结果，70例发生脊柱转移患者纳入转移组，104例未发生脊柱转移患者纳入无转移组，两组患者的性别、年龄、吸烟、高血压、血栓形成、肿瘤位置均无统计学差异（P＞0.05）。收集并比较两组患者的病理类型、临床分期、淋巴结转移、肿瘤直径。采用qRT-PCR检测血清miR-550a-5p表达水平，酶联免疫吸附法检测血清抗酒石酸酸性磷酸酶-5b（tartrate-resistant acid phosphatase-5b，TRACP-5b）和Ⅰ型胶原交联C端肽（type Ⅰ collagen cross-linked C-terminal peptide，ICTP）水平，比较两组血清TRACP-5b、ICTP、miR-550a-5p水平差异。采用受试者工作特征（receiver operating characteristic，ROC）曲线评估单独miR-550a-5p、TRACP-5b、ICTP及联合使用时对NSCLC患者脊柱转移的诊断价值。结果：与无转移组相比，转移组患者血清TRACP-5b、ICTP、miR-550a-5p水平显著性升高（P<0.05）；肿瘤直径≥5cm肺腺癌、Ⅲ-Ⅳ期、淋巴结转移患者miR-550a-5p水平显著性高于肿瘤直径＜5cm、鳞癌、Ⅰ-Ⅱ期、无淋巴结转移患者（P＜0.05）。血清miR-550a-5p升高、肺腺癌、Ⅲ-Ⅳ期、淋巴结转移均是NSCLC患者发生脊柱转移的独立危险因素（P<0.05）。单独应用miR-550a-5p诊断NSCLC患者脊柱转移的AUC为0.851，最佳截断值为0.20时，灵敏度和特异度分别为74.29%、85.58%；单独应用血清miR-550a-5p诊断NSCLC患者脊柱转移的诊断效能明显优于TRACP-5b（Z=2.309，P=0.023）和ICTP（Z=1.852，P=0.049）。miR-550a-5p、TRACP-5b、ICTP三项联合诊断NSCLC患者脊柱转移的AUC为0.931，灵敏度和特异度分别为88.57%、87.50%；三项联合的诊断效能明显优于TRACP-5b和ICTP二项联合（Z=2.205，P=0.027）。结论：血清miR-550a-5p水平升高与NSCLC患者脊柱转移有关，可作为预测NSCLC患者脊柱转移的分子标志物，且其与骨代谢相关肿瘤标志物ICTP和TRACP-5b联合应用能够提高诊断效能。

英文摘要:

  【Abstract】 Objectives: To investigate the relationship between serum miR-550a-5p levels and spinal metastasis in patients with non-small cell lung cancer (NSCLC). Methods: The clinical data of 175 patients with NSCLC who received treatment in the Affiliated Hospital of Chengde Medical College between May 2021 and May 2023 were retrospectively analyzed. According to the results of whole body bone imaging, 70 patients with spinal metastasis were enrolled into the metastasis group, and 104 patients without spinal metastasis were enrolled into the none-metastasis group. There were no statistically significant differences in gender, age, smoking, hypertension, thrombosis, and tumor location between the two groups(P>0.05). The pathological type, clinical stage, lymph node metastasis, and tumor diameter of the patients were collected and compared between the two groups. qRT-PCR was used to detect the expression level of serum miR-550a-5p, enzyme-linked immunosorbent assay was used to detect the serum tartrate-resistant acid phosphatase-5b (TRACP-5b) and type Ⅰ collagen cross-linked C-terminal peptide (ICTP) levels. The differences in serum levels of TRACP-5b, ICTP, and miR-550a-5p were compared between the two groups. The receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic value of miR-550a-5p, TRACP-5b, and ICTP alone and in combination for spinal metastasis in NSCLC patients. Results: Compared with the none-metastasis group, serum TRACP-5b, ICTP, and miR-550a-5p levels were significantly higher in patients in the metastasis group(P<0.05). The miR-550a-5p level was significantly higher in patients with tumor diameter≥5cm, lung adenocarcinoma, stage Ⅲ-Ⅳ, and lymph node metastasis than in patients with tumor diameter＜5cm, squamous carcinoma, stage Ⅰ-Ⅱ, and no lymph node metastasis(P<0.05). Elevated serum miR-550a-5p, lung adenocarcinoma, stage Ⅲ-Ⅳ, and lymph node metastasis were the independent risk factors for the development of spinal metastasis in NSCLC patients(P<0.05). The AUC of miR-550a-5p for diagnosing spinal metastasis in NSCLC patients was 0.851, and the sensitivity and specificity were 74.29% and 85.58%, respectively, at the optimal cut-off value of 0.20. The diagnostic efficacy of serum miR-550a-5p for diagnosing spinal metastasis in NSCLC patients was significantly better than that of TRACP-5b(Z=2.309, P=0.023) and ICTP(Z=1.852, P=0.049). The AUC of miR-550a-5p, TRACP-5b, and ICTP combination for the diagnosis of spinal metastasis in NSCLC patients was 0.931, and the sensitivity and specificity were 88.57% and 87.50%, respectively. The diagnostic efficacy of the three-marker combination was significantly better than that of the two-marker combination of TRACP-5b and ICTP(Z=2.205, P=0.027). Conclusions: Elevated level of serum miR-550a-5p is associated with spinal metastasis, which can be used as a molecular marker for predicting spinal metastasis in NSCLC patients, moreover, its combination use with bone metabolism-related tumor markers, the ICTP and TRACP-5b, can improve diagnostic efficacy.