第一临床医学院知识库

背景/目的：在全世界范围内，胃癌是最常见的消化系统癌症之一，并因其高发病率和高死亡率而备受关注。胃癌的早诊断早治疗是解决这一难题的关键措施，但是目前有创性的胃镜检查难以普及，而传统的应用最广的肿瘤标记物用于诊断胃癌其特异性和敏感性又相对不足。循环miRNAs因其在体液中稳定存在，有希望成为理想的肿瘤诊断指标，一直是近年研究的热点。本研究的目的在于探索miR-551b-3p在术前胃癌患者血清中的表达水平，比较胃癌患者组与健康对照组血清中miR-551b-3p的表达量变化情况，分析胃癌患者血清miR-551b-3p的表达水平与其临床病理特征的关联，并探讨其对于胃癌诊断的临床意义。

方法：本研究收集50例经病理活检确诊的胃癌病人及53例健康人的血清标本。用Trizol法提取胃癌患者血清及健康人血清中的总RNA，反转录后以miR-16作为内参，运用实时荧光定量PCR（qRT-PCR）方法检测血清中miR-551b-3p的表达量，比较其在胃癌血清组和健康对照血清组中表达量的差异，并对胃癌患者血清miR-551b-3p的表达水平与相应病人的临床病理特征的相关性进行分析，探究其对于胃癌诊断的临床意义。

结果：（1）与健康对照组血清水平相比，miR-551b-3p在胃癌患者血清中的表达水平显著降低（P=0.000）。（2）胃癌患者血清miR-551b-3p低水平与胃癌的肿瘤直径（P=0.014），局部浸润深度（P=0.001）及临床TNM分期显著相关（P=0.022），而与胃癌患者的性别、年龄、肿瘤分化程度、淋巴结是否转移等无明显关联（P>0.05）。（3）血清miR-551b-3p作为胃癌诊断标志物的诊断效能评估：ROC曲线下面积AUC=0.860，P=0.000（95%可信区间CI：0.787-0.933），利用约登指数（YI）0.662，算出最佳诊断界值为0.0175，当血清miR-551b-3p的相对表达量低于此界值判定为胃癌，此法灵敏度70%，特异度96.2%，诊断符合率83.5%，误诊率3.8%，漏诊率30%，阳性预测值94.6%，阴性预测值77.3%。与当前胃癌诊断金标准进行一致性检验后结果显示kappa值0.667（P=0.000）。（4）血清miR-551b-3p对胃癌肿瘤直径的诊断效能评估：ROC曲线下面积AUC=0.702，P=0.014（95%可信区间CI：0.556-0.847），灵敏度80.8%，特异度58.3%；对局部浸润深度诊断效能评估：AUC=0.792，P=0.000（95%可信区间CI：0.652-0.929），灵敏度87.1%，特异度68.4%；对临床TNM分期诊断效能评估：AUC=0.690，P=0.022（95%可信区间CI：0.543-0.836），灵敏度90.9%，特异度53.6%。
结论：胃癌患者血清miR-551b-3p表达水平相较于健康人显著下调，其表达量与胃癌肿瘤直径、局部浸润深度及临床TNM分期相关性显著。其血清表达水平对胃癌患者的诊断有参考价值，而与病理活检结果诊断一致性水平较好。同时，血清miR-551b-3p对胃癌直径、局部浸润深度及临床TNM分期也有一定的诊断价值。故血清miR-551b-3p对于胃癌的临床诊断有重要的参考价值。

Background/Objective: Gastric cancer is one of the most common malignant tumors of digestive system in the world. Gastric cancer has attracted much attention because of its high morbidity and mortality The early diagnosis and treatment of gastric cancer is the key to solve the difficult problem. However, the current invasive gastroscopy is difficult to popularize and the traditional and most widely used tumor biomarkers are relatively less specific and sensitive for the diagnosis of gastric cancer. Because of miRNAs stable existence in body fluid, they had the potential to be ideal circulating tumor biomarkers and had been a hot spot in recent years. The objective of this study was to investigate the expression of miR-551b-3p in serum of gastric cancer patients and to compare the changes of serum miR-551b-3p expression in gastric cancer patients and healthy controls. We analyzed the correlation of serum miRNA-551b- 3p expression and the clinicopathological parameters of gastric cancer patients, and explored its clinical significance for the diagnosis of gastric cancer.

Methods: In this study, serum samples of 50 patients with pathologically diagnosed gastric cancer and 53 healthy individuals were collected. Total RNA was extracted from serum of patients with gastric cancer and healthy controls by Trizol. Reverse transcription was performed. We used miR-16 as an internal control in this study. The expression of miR-551b-3p in serum was detected by real-time fluorescence quantitative PCR (qRT-PCR). We compared the serum expression of miR-551b-3p in gastric cancer patients and normal controls. The difference between the expression of miR-551b-3p and the clinicopathological characteristics of gastric cancer patients was analyzed.

Results:(1) The expression of miR-551b-3p in serum of patients with gastric cancer was significantly lower than healthy controls (P = 0.000).(2)The low level of serum miR-551b-3p in patients with gastric cancer was significantly correlated with tumor diameter (P = 0.014), depth of invasion (P = 0.001) and TNM stage (P = 0.022). And there was no significant correlation with age, gender, tumor differentiation and lymph node metastasis(P> 0.05).(3)The diagnostic efficacy of serum miR-551b-3p as a diagnostic biomarker for gastric cancer: The area under the ROC curve was 0.860, P = 0.000 (95% confidence interval: 0.787-0.933), Youden index was 0.662. The best cutoff was 0.0175. When the relative expression level of serum miR-551b-3p in gastric cancer patients was lower than the cut off, the sensitivity was 70%, the specificity was 96.2%,the misdiagnosis rate (α) was 3.8%, the omission diagnostic rate (β) was 30%, the diagnostic coincidence rate (π) was 83.5%, the positive predictive value (PV+) was 94.6%, the negative predictive value (PV-) was 77.3%.The results of the consistency test with the current gold standard of gastric cancer diagnosis indicated kappa value was 0.667 (P = 0.000).(4)The diagnostic efficacy of serum miR-551b-3p in the diameter of gastric cancer was evaluated: the area under the ROC curve was AUC=0.702, P=0.014 (95% CI: 0.556-0.847), the sensitivity was 80.8% and the specificity was 58.3%; Infiltration depth diagnostic evaluation: AUC=0.792, P=0.000 (95% CI: 0.652-0.929), the sensitivity was 87.1% and the specificity was 68.4%; Evaluation of clinical TNM staging effectiveness: AUC=0.690, P=0.022 (95% CI: 0.543-0.836), the sensitivity was 90.9% and the specificity was 53.6%.

Conclusion: The expression of serum miR-551b-3p in patients with gastric cancer is significantly lower than that healthy controls. The expression of miR-551b-3p is significantly correlated with tumor diameter, depth of invasion and TNM stage, and its diagnostic accuracy and the diagnostic consistency for gastric cancer is good. Serum miR-551b-3p also has certain diagnostic value for tumor diameter, depth of invasion and TNM stag of gastric cancer. Therefore, serum miR-551b-3p has important reference value for the clinical diagnosis of gastric cancer.