摘要目的:探讨非小细胞肺癌（NSCLC）癌组织中微RNA-4262（miR-4262）、神经调节素1（NRG1）的表达情况及与预后的关系。方法:选取2017年1月至2021年2月在贵州省铜仁市人民医院进行手术切除的NSCLC患者102例，采用实时荧光定量PCR法检测miR-4262、NRG1的表达情况，分析NSCLC癌组织和癌旁组织以及不同临床病理特征NSCLC患者癌组织中miR-4262、NRG1表达水平。通过TargetScan数据库预测miR-4262与NRG1的结合位点，Pearson相关系数分析NSCLC癌组织中miR-4262、NRG1表达的相关性。以NSCLC癌组织中miR-4262、NRG1表达水平的均数为界，将患者分为miR-4262高表达组（miR-4262≥1.52， n=54）和miR-4262低表达组（miR-4262<1.52， n=48）、NRG1高表达组（NRG1≥0.79， n=54）和NRG1低表达组（NRG1<0.79， n=48）。绘制Kaplan-Meier生存曲线，比较高、低miR-4262、NRG1表达水平患者3年总生存（OS）率。采用Cox比例风险回归模型分析NSCLC患者预后的影响因素。 结果:NSCLC患者癌组织中miR-4262的表达水平（1.52±0.21）高于癌旁组织（1.11±0.20），NRG1表达水平（0.79±0.11）低于癌旁组织（1.06±0.11），差异均有统计学意义（ t=14.22， P<0.001； t=-15.13， P<0.001）。NSCLC患者癌组织中miR-4262与NRG1表达呈负相关（ r=-0.74， P<0.001）。不同分化程度（ t=2.80， P=0.006； t=-2.80， P=0.006）、TNM分期（ F=24.36， P<0.001； F=17.66， P<0.001）、淋巴结转移（ t=4.02， P<0.001； t=-3.98， P<0.001）的NSCLC患者miR-4262、NRG1表达水平差异均有统计学意义。截至随访截止日期，102例NSCLC患者中，存活57例，死亡45例。NSCLC患者3年OS率为55.88%。miR-4262高表达患者3年OS率（35.19%）低于miR-4262低表达患者（79.17%），NRG1高表达患者3年OS率（77.78%）高于NRG1低表达患者（31.25%），差异均有统计学意义（ χ2=22.58， P<0.001； χ2=27.26， P<0.001）。单因素分析显示，年龄（ HR=2.47，95% CI为1.05~5.80， P=0.038）、肿瘤最大径（ HR=3.75，95% CI为1.61~8.74， P=0.002）、分化程度（ HR=3.03，95% CI为1.32~6.96， P=0.009）、TNM分期（Ⅱ期 HR=3.45，95% CI为1.10~10.83， P=0.034；Ⅲ期 HR=6.72，95% CI为2.03~22.26， P=0.002）、淋巴结转移（ HR=3.00，95% CI为1.29~6.96， P=0.010）、miR-4262表达（ HR=3.72，95% CI为1.48~9.35， P=0.005）、NRG1表达（ HR=0.30，95% CI为0.13~0.73， P=0.008）均是NSCLC患者OS的影响因素。多因素分析显示，分化程度（ HR=5.47，95% CI为1.63~18.34， P=0.006）、TNM分期（Ⅲ期， HR=5.56，95% CI为1.23~25.14， P=0.026）、淋巴结转移（ HR=3.72，95% CI为1.19~11.60， P=0.024）、miR-4262表达（ HR=8.56，95% CI为2.26~32.41， P=0.002）、NRG1表达（ HR=0.26，95% CI为0.09~0.76， P=0.014）均是NSCLC患者OS的独立影响因素。 结论:NSCLC患者癌组织中miR-4262呈高表达，NRG1呈低表达，miR-4262高表达患者3年OS率低于miR-4262低表达患者，NRG1高表达患者3年OS率高于NRG1低表达患者，分化程度、TNM分期、淋巴结转移、miR-4262、NRG1均是NSCLC患者预后的独立影响因素。

abstractsObjective:To investigate the expression of microRNA-4262 (miR-4262) and neuregulin 1 (NRG1) in non-small cell lung cancer (NSCLC) tissues and the relationship with prognosis.Methods:A total of 102 NSCLC patients who underwent surgical resection from January 2017 to February 2021 in Tongren People's Hospital of Guizhou Province were selected. The expression levels of miR-4262 and NRG1 were detected using real-time fluorescence quantitative PCR. The expression levels of miR-4262 and NRG1 in NSCLC cancer tissues and adjacent tissues, as well as NSCLC cancer tissues with different clinicopathological characteristics were analyzed. TargetScan database was used to predict the binding sites of miR-4262 and NRG1, and Pearson correlation coefficient was used to analyze the correlation between miR-4262 and NRG1 expression in NSCLC cancer tissues. Based on the mean expression levels of miR-4262 and NRG1 in NSCLC cancer tissues, the patients were divided into high miR-4262 expression group (miR-4262≥1.52, n=54) and low miR-4262 expression group (miR-4262<1.52, n=48), high NRG1 expression group (NRG1≥0.79, n=54) and low NRG1 expression group (NRG1<0.79, n=48). Kaplan-Meier survival curves were plotted to compare the 3-year overall survival (OS) rates between groups. Cox proportional risk regression model was used to analyze the influencing factors for the prognosis of NSCLC patients. Results:The expression level of miR-4262 was significantly higher in NSCLC tumor tissues compared to adjacent tissues (1.52±0.21 vs. 1.11±0.20), while NRG1 expression level was lower (0.79±0.11 vs. 1.06±0.11), there were statistically significant differences ( t=14.22, P<0.001; t=-15.13, P<0.001). The expression of miR-4262 was negatively correlated with NRG1 in cancer tissues of NSCLC patients ( r=-0.74, P<0.001). There were statistically significant differences in the expression levels of miR-4262 and NRG1 of NSCLC patients in tumor differentiation ( t=2.80, P=0.006; t=-2.80, P=0.006), TNM stage ( F=24.36, P<0.001; F=17.66, P<0.001), and lymph node metastasis ( t=4.02, P<0.001; t=-3.98, P<0.001). At the end of the follow-up period, 57 patients survived, and 45 died, with a 3-year OS rate of 55.88%. Patients with high miR-4262 expression had a significantly lower 3-year OS rate compared to those with low miR-4262 expression (35.19% vs. 79.17%), patients with high NRG1 expression had a significantly higher 3-year OS rate than those with low NRG1 expression (77.78% vs. 31.25%), there were statistically significant differences ( χ2=22.58, P<0.001; χ2=27.26, P<0.001). Univariate analysis showed that, age ( HR=2.47, 95% CI: 1.05-5.80, P=0.038), maximum tumor diameter ( HR=3.75, 95% CI: 1.61-8.74, P=0.002), differentiation degree ( HR=3.03, 95% CI: 1.32-6.96, P=0.009), TNM stage (stage Ⅱ, HR=3.45, 95% CI: 1.10-10.83, P=0.034; stage Ⅲ, HR=6.72, 95% CI: 2.03-22.26, P=0.002), lymph node metastasis ( HR=3.00, 95% CI: 1.29-6.96, P=0.010), miR-4262 expression ( HR=3.72, 95% CI: 1.48-9.35, P=0.005), and NRG1 expression ( HR=0.30, 95% CI: 0.13-0.73, P=0.008) were all influencing factors for OS in NSCLC patients. Multivariate analysis showed that, differentiation degree ( HR=5.47, 95% CI: 1.63-18.34, P=0.006), TNM stage (stage Ⅲ, HR=5.56, 95% CI: 1.23-25.14, P=0.026), lymph node metastasis ( HR=3.72, 95% CI: 1.19-11.60, P=0.024), miR-4262 expression ( HR=8.56, 95% CI: 2.26-32.41, P=0.002), and NRG1 expression ( HR=0.26, 95% CI: 0.09-0.76, P=0.014) were all independent influencing factors for OS in NSCLC patients. Conclusions:The expression of miR-4262 is high and the expression of NRG1 is low in cancer tissues of NSCLC patients. The 3-year OS rate of patients with high miR-4262 expression is lower than that of patients with low miR-4262 expression, and the 3-year OS rate of patients with high NRG1 expression is higher than that of patients with low NRG1 expression. Differentiation degree, TNM stage, lymph node metastasis, miR-4262 and NRG1 are all independent influencing factors for the prognosis of NSCLC patients.