幽门螺杆菌相关胃癌中miR-145表达及临床意义★

Expression of miR-145 in Helicobacter pylori-related gastric cancer and its clinical significance★

摘要:

目的 分析幽门螺杆菌（H.pylori， Hp）相关胃癌中miR-145的表达及临床意义。方法 选取本院2019年6月—2022年12月接诊的86例胃癌患者，根据是否存在Hp感染将其分为两组，56例Hp阳性患者为观察组，30例Hp阴性患者为对照组。取患者癌组织及癌旁组织，检测miR-145表达，比较两组患者癌组织及癌旁组织中miR-145表达量，比较不同病理特征Hp阳性患者的miR-145表达量。抽取两组患者空腹静脉血5 mL，检测血清C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）水平，绘制接受者操作特征（ROC）曲线，计算曲线下面积（AUC），比较CRP、TNF-α、miR-145对Hp阳性胃癌的诊断价值。Pearson分析miR-145与CRP、TNF-α的相关性。随访3年，比较存活组、死亡组miR-145表达量。采用Kaplan-Meier法进行生存分析，Graph Pad Prism 8.0绘制miR-145高表达组、低表达组生存曲线。结果 观察组患者癌组织及癌旁组织中miR-145的表达量均显著低于对照组（P<0.05）。不同性别、年龄、肿瘤大小的Hp阳性胃癌患者miR-145表达量比较，差异无统计学意义（P>0.05），远处转移、淋巴结转移、浸润深度T3~T4、Ⅲ~Ⅳ期Hp阳性胃癌患者miR-145表达量均显著低于无远处转移、无淋巴结转移、浸润深度T1~T2、Ⅰ~Ⅱ期患者（P<0.05）。观察组患者血清CRP、TNF-α水平均显著高于对照组（P<0.05）。miR-145与CRP、TNF-α的表达均呈负相关（r=-0.493， P<0.05；r=-0.482， P<0.05）。ROC曲线显示：miR-145的诊断灵敏度（90.24%）、特异度（89.28%）明显高于CRP（75.82%， 76.28%）和TNF-α（77.37%， 78.17%）（P<0.05）。随访3年，86例患者无脱落病例，中位生存时间30.52个月，3年生存率为58.14%。存活组患者癌组织及癌旁组织中miR-145表达量显著高于死亡组（P<0.05），miR-145高表达组患者生存率高于miR-145低表达组（P<0.05）。结论 胃癌患者miR-145表达量较低，尤其是感染Hp的患者，miR-145表达量更低；Hp相关胃癌患者的临床病理特征、炎症反应与miR-145表达存在一定关系，临床可通过检测miR-145表达量评估疾病进程和炎症反应，提高诊断灵敏度、特异度；miR-145低表达可能影响Hp相关胃癌患者疾病转归与预后。

Abstract:

Objective To analyze the expression and clinical significance of microRNA-145 (miR-145) in Helicobacter pylori (Hp)-related gastric cancer.Methods The study enrolled 86 patients diagnosed with gastric cancer and treated at our hospital between June 2019 and December 2022. The patients were stratified into two cohorts based on the presence or absence of Hp infection, with 56 Hp-positive patients assigned to the observation group and 30 Hp-negative patients assigned to the control group. Tissue samples from both cancerous and adjacent non-cancerous tissues were collected for miR-145 expression analysis. Comparative assessments of miR-145 expression in cancerous and adjacent non-cancerous tissues were conducted between the two patient groups, as well as among Hp-positive patients with different pathological features. Blood samples (5 mL venous blood) were collected from all patients prior to meals, and the levels of serum C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were quantified and compared between the two groups. Receiver operating characteristic (ROC) curves were conducted and the area under the curve (AUC) was computed to compare the diagnostic efficacy of CRP, TNF-α, and miR-145 for Hp-positive gastric cancer. Pearson analysis was employed to assess the correlation between miR-145 and CRP as well as TNF-α. After 3 years of follow-up, the expression levels of miR-145 were compared between the survival group and the death group. Kaplan-Meier method was used to calculate the survival rate, and Graph Pad Prism 8.0 was used to plot the survival curves of miR-145 high-expression group and low-expression group.Results The expression levels of miR-145 in cancer tissues and adjacent tissues of the observation group were significantly lower than those of the control group (P<0.05). There was no significant difference in the expression of miR-145 among Hp-positive gastric cancer patients of different gender, age and tumor sizes (P>0.05). The expression of miR-145 in Hp-positive gastric cancer patients with distant metastasis, lymph node metastasis, infiltration depth of T3~T4, or stages III~IV was significantly lower than that in patients without distant metastasis, without lymph node metastasis, with infiltration depth of T1~T2, and stages I~II (P<0.05). The levels of CRP and TNF-α in the serum of observation group were higher than those of the control group (P<0.05). miR-145 was negatively correlated with CRP and TNF-α(r=-0.493, P<0.05;r=-0.482, P<0.05). The ROC curve showed that the diagnostic sensitivity (90.24%) and specificity (89.28%) for miR-145 were significantly higher than those for CRP (75.82%, 76.28%) and TNF-α (77.37%, 78.17%) (P<0.05). During the 3-year follow-up, there were no lost cases, and the median survival time was 30.52 months, with a three-year survival rate being 58.14%. The expression of miR-145 in the cancer tissue and adjacent tissue of the survival group was significantly higher than that in the death group (P<0.05). The survival rate of the group with high miR-145 expression was higher than that of the group with low miR-145 expression (P<0.05).Conclusion In patients with gastric cancer, the expression level of miR-145 is significantly reduced, particularly in those infected with Hp, where it is further diminished. The clinical and pathological characteristics, inflammatory response, and miR-145 expression in Hp-related gastric cancer patients are interrelated. Clinically, the miR-145 expression level can serve as an indicator for disease progression and inflammatory response assessment, thereby enhancing diagnostic sensitivity and specificity. Low expression of miR-145 may impact the disease outcome and prognosis of Hp-related gastric cancer patients.