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中华临床医师杂志(电子版) ›› 2022, Vol. 16 ›› Issue (06) : 529 -535. doi: 10.3877/cma.j.issn.1674-0785.2022.06.012

临床研究

血清miR-146b-3p、miR-15b-5p、miR-16-5p在良恶性肺结节鉴别诊断、预后评估中的价值
曹炜1, 赵大海2,†(), 赵旭东1   
  1. 1. 230601　安徽合肥，安徽医科大学第二附属医院胸外科
    2. 230601　安徽合肥，安徽医科大学第二附属医院呼吸与危重医学科
  • 收稿日期:2021-09-15 出版日期:2022-06-15
  • 通信作者: 赵大海
  • 基金资助:
    合肥市自然科学基金项目(2021037)

Value of serum miR-146b-3p, miR-15b-5p, and miR-16-5p in differential diagnosis and prognosis evaluation of benign and malignant pulmonary nodules

Wei Cao1, Dahai Zhao2,†(), Xudong Zhao1   

  1. 1. Department of Thoracic Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
    2. Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
  • Received:2021-09-15 Published:2022-06-15
  • Corresponding author: Dahai Zhao
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引用本文：

曹炜, 赵大海, 赵旭东. 血清miR-146b-3p、miR-15b-5p、miR-16-5p在良恶性肺结节鉴别诊断、预后评估中的价值[J/OL]. 中华临床医师杂志(电子版), 2022, 16(06): 529-535.

Wei Cao, Dahai Zhao, Xudong Zhao. Value of serum miR-146b-3p, miR-15b-5p, and miR-16-5p in differential diagnosis and prognosis evaluation of benign and malignant pulmonary nodules[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(06): 529-535.

目的

探究微小RNA（miR）-146b-3p、miR-15b-5p、miR-16-5p在良恶性肺结节鉴别诊断以及预后评估中价值。

方法

前瞻性选择2018年6月至2020年6月期间安徽医科大学第二附属医院收治139例肺结节患者作为研究对象，行病理检查或者穿刺活检后确定患者病灶良恶性，其中良性组75例，恶性组64例。2组患者均测定血清miR-146b-3p、miR-15b-5p、miR-16-5p。分析上述指标在患者良恶性结节诊断上价值，恶性组患者血清miR-146b-3p、miR-15b-5p、miR-16-5p与患者病理特征之间关系。随访评估恶性组患者预后，分析血清miR-146b-3p、miR-15b-5p、miR-16-5p对预后预测价值。

结果

良性组患者血清miR-146b-3p、miR-15b-5p显著低于恶性组（P＜0.05），miR-16-5p显著高于恶性组（P＜0.05）。受试者工作特征（ROC）曲线显示，血清miR-146b-3p、miR-15b-5p、miR-16-5p及各种指标联合对于结节良恶性诊断曲线下面积（AUC）分别为0.803、0.786、0.889、0.962。血清miR-146b-3p、miR-15b-5p、miR-16-5p与分化程度、淋巴结转移、临床分期类型有关（P＜0.05）；Spearman相关性分析显示，血清miR-146b-3p、miR-15b-5p均与分化程度呈显著的负相关，且均有统计学意义（r=-0.534，-0.468；P＜0.05），均与淋巴结转移呈显著的正相关，且均有统计学意义（r=0.582，0.608；P＜0.05），均与临床分期类型呈显著的正相关（r=0.486，0.519；P＜0.05）；miR-16-5p与分化程度、淋巴结转移、临床分期分别呈显著的正相关、负相关、负相关（r=0.412，-0.563，-0.657；P＜0.05），且均有统计学意义。预后不良恶性组患者血清miR-146b-3p、miR-15b-5p显著高于恶性组，miR-16-5p显著高于预后良好患者，且上述差异均有统计学意义（P＜0.05）。ROC曲线显示，血清miR-146b-3p、miR-15b-5p、miR-16-5p及各指标联合对于恶性结节患者预后预测AUC分别为0.799、0.772、0.554、0.837。

结论

血清miR-146b-3p、miR-15b-5p、miR-16-5p与肺结节良恶性、恶性结节临床特征以及恶性结节患者预后关系密切，三种血清指标联合用于肺结节良恶性鉴别诊断以及预后预测价值优异。

关键词: 血清微RNA, 肺结节, 良恶性鉴别诊断, 预后评估
Objective

To evaluate the value of microRNA (miR)-146b-3p, miR-15b-5p, and miR-16-5p in the differential diagnosis and prognosis evaluation of benign and malignant pulmonary nodules.

Methods

Totally 139 patients with pulmonary nodules admitted to our hospital were selected as the research subjects between June 2018 and June 2020. Based on postoperative pathological results or biopsy results, the patients were divided into a benign group (n=75) and a malignant group (n=64). Serum miR-146b-3p, miR-15b-5p, and miR-16-5p in the two groups were measured, and their diagnostic value in benign and malignant nodules was analyzed. The relationship between serum miR-146b-3p, miR-15b-5p, or miR-16-5p and pathological characteristics in the malignant group was analyzed. The prognosis of patients in the malignant group was evaluated, and the prognostic value of serum miR-146b-3p, miR-15b-5p, and miR-16-5p was analyzed.

Results

Serum miR-146b-3p and miR-15b-5p in the benign group were significantly lower than those in the malignant group (P＜0.05), and miR-16-5p was significantly higher than that in the malignant group (P＜0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) values of serum miR-146b-3p, miR-15b-5p, and miR-16-5p, alone and in combination, to diagnose benign and malignant nodules were 0.803, 0.786, 0.889, and 0.962, respectively. Serum miR-146b-3p, miR-15b-5p, and miR-16-5p were related to differentiation degree, lymph node metastasis, and clinical stage (P＜0.05). Spearman correlation analysis showed that both serum miR-146b-3p and miR-15b-5p were significantly negatively correlated with differentiation degree (r=-0.534 and -0.468, respectively, P＜0.05), and significantly positively correlated with lymph node metastasis (r=0.582 and 0.608, respectively, P＜0.05) and clinical stage (r=0.486 and 0.519, respectively, P＜0.05). Serum miR-16-5p was significantly positively correlated with differentiation degree, and significantly negatively correlated with lymph node metastasis and clinical stage (r=0.412, -0.563, and -0.657, respectively, P＜0.05). In the malignant group, serum miR-146b-3p and miR-15b-5p in patients with a poor prognosis were significantly higher than those in patients with a good prognosis, and miR-16-5p was significantly lower in patients with a poor prognosis than that in patients with a good prognosis (P＜0.05). ROC curve analysis showed that the AUC values of serum miR-146b-3p, miR-15b-5p, miR-16-5p, alone and in combination, for evaluating the prognosis of patients with malignant nodules were 0.799, 0.772, 0.774, and 0.881, respectively.

Conclusion

Serum miR-146b-3p, miR-15b-5p, and miR-16-5p are closely related to clinical characteristics of benign and malignant pulmonary nodules and the prognosis of patients with malignant nodules. Combination of the three is of high value in the differential diagnosis of benign and malignant pulmonary nodules.

Key words: Serum microRNA, Pulmonary nodule, Differential diagnosis of benign and malignant, Prognosis evaluation
表1 比较良恶性结节血清miRNA水平（
xˉ
±s）
组别 例数 miR-146b-3p miR-15b-5p miR-16-5p
良性组 75 0.64±0.21 7.64±1.44 26.25±3.37
恶性组 64 0.96±0.32 10.07±2.95 19.27±5.24.
t值 7.242 6.954 9.470
P值 ＜0.001 ＜0.001 ＜0.001
表2 血清miRNA水平对于结节良恶性诊断价值分析
指标 截断值 AUC 敏感度 特异度 95%CI P值
miR-146b-3p 0.84 0.803 64.1 86.7 0.727~0.879 ＜0.001
miR-15b-5p 9.15 0.786 56.3 96.0 0.704~0.867 ＜0.001
miR-16-5p 22.43 0.889 79.7 90.7 0.831~0.947 ＜0.001
各指标联合 - 0.962 87.5 93.3 0.933~0.991 ＜0.001
图1 血清miRNA水平对于结节良恶性诊断价值分析
表3 比较恶性组不同病理资料患者血清miRNA水平（
xˉ
±s）
病理资料 例数 miR-146b-3p t值 P值 miR-15b-5p t值 P值 miR-16-5p t值 P值
年龄（岁） 0.256 0.799 0.231 0.818 0.322 0.748
＜60 24 0.95±0.29 9.97±2.53 19.03±4.21
≥60 40 0.97±0.31 10.13±2.76 19.41±4.76
性别 0.407 0.686 0.191 0.849 1.666 0.101
男 39 0.97±0.28 10.12±2.74 18.53±4.26
女 25 0.94±0.30 9.99±2.51 20.42±4.68
吸烟史 1.054 0.296 1.036 0.304 0.410 0.683
是 35 0.99±0.26 9.75±2.66 19.08±4.22
否 29 0.92±0.27 10.46±2.81 19.50±3.91
组织学类型 0.497 0.621 0.843 0.402 1.344 0.184
腺癌 43 0.95±0.22 9.86±2.75 19.69±3.25
鳞状细胞癌 21 0.98±0.24 10.50±3.05 18.41±4.18
病灶尺寸（cm） 0.315 0.754 0.156 0.877 1.032 0.306
＜3 23 0.97±0.25 10.14±2.66 18.56±3.27
≥3 41 0.95±0.24 10.03±2.74 19.67±4.53
分化程度 22.889 ＜0.001 17.966 ＜0.001 32.498 ＜0.001
低分化 20 1.25±0.31 12.34±3.15 14.81±3.91
中分化 26 0.89±0.24 10.07±2.09 19.77±2.84
高分化 18 0.74±0.19 7.55±1.79 23.50±2.36
淋巴结转移 4.083 ＜0.001 5.054 ＜0.001 4.122 ＜0.001
是 28 1.09±0.24 11.97±2.51 17.50±4.19
否 36 0.86±0.21 8.59±2.76 20.65±3.66
临床分期类型 2.368 0.021 5.242 ＜0.001 4.632 ＜0.001
Ⅰ+Ⅱ 36 0.89±0.22 8.56±2.15 21.32±3.51
Ⅲ+Ⅳ 28 1.05±0.32 12.01±3.11 16.63±4.19
表4 比较不同预后恶性组患者血清miRNA水平（
xˉ±s
）
组别 例数 miR-146b-3p miR-15b-5p miR-16-5p
预后不良组 23 1.15±0.29 13.42±4.52 15.55±4.56
预后良好组 41 0.85±0.31 8.19±2.56 21.36±4.40
t值 4.575 4.482 5.003
P值 ＜0.001 ＜0.001 ＜0.001
表5 分析血清miRNA水平对于恶性结节患者预后预测价值
指标 截断值 AUC 敏感度 特异度 95% CI P值
miR-146b-3p 0.97 0.799 78.3 80.5 0.686~0.912 ＜0.001
miR-15b-5p 9.54 0.772 78.3 70.7 0.638~0.906 ＜0.001
miR-16-5p 17.66 0.554 52.2 63.4 0.424~0.678 0.480
各指标联合 - 0.837 60.9. 97.6 0.727~0.947 ＜0.001
图2 血清miRNA水平对于恶性结节患者预后预测价值分析ROC曲线
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