肺癌患者围化疗期SIRT3、ATF2的表达变化对预后的预测价值

Predictive value of SIRT3 and ATF2 expression changes on prognosis in patients with lung cancer during perioperative chemotherapy

目的分析肺癌患者围化疗期去乙酰化酶3(SIRT3)、激活转录因子2(ATF2)的表达变化对预后的预测价值。方法回顾性选取2018年1月至2021年1月在汉中市中心医院进行化疗的80例肺癌患者作为研究对象,于化疗前后采用免疫组织化学法检测SIRT3、ATF2表达情况,分析SIRT3、ATF2高、低表达与肺癌病理特征的关系;并采用实时荧光定量PCR(qRT-PCR)检测不同预后患者的SIRT3、ATF2表达水平,建立多因素Logistic模型分析影响肺癌化疗预后独立危险因素,同时分析SIRT3、ATF2在肺癌化疗预后中的预测价值。结果80例肺癌SIRT3高表达、低表达率分别为42.50%、57.50%,ATF2高表达、低表达率分别为55.00%、45.00%。肺癌SIRT3和ATF2高表达、低表达率比较,差异无统计学意义(P>0.05)。SIRT3高表达TNM>Ⅲ期、有淋巴结转移的患者比率分别为9.09%、25.00%,均显著低于SIRT3低表达(90.91%、75.00%),差异均有统计学意义(P<0.05);肺癌患者ATF2高表达TNM>Ⅲ期、有淋巴结转移的患者比率分别为95.45%、71.43%,均显著高于ATF2低表达(4.55%、28.57%),差异均有统计学意义(P<0.05)。80例肺癌患者中,预后良好组52例,预后不良组28例。化疗后,预后不良组患者SIRT3 mRNA表达水平为1.74±0.13,高于预后良好组(1.41±0.11),ATF2 mRNA表达水平为0.25±0.04,低于预后良好组(0.34±0.04),差异均有统计学意义(P<0.05)。多因素Logistic分析结果显示,TNM分期、淋巴结转移、SIRT3、ATF2均是影响肺癌化疗预后的独立危险因素(P<0.05)。SIRT3、ATF2、SIRT3+ATF2在肺癌化疗预后预测中的曲线下面积(AUC)均>0.80,且发现SIRT3+ATF2联合预测AUC为0.896,大于SIRT3、ATF2的0.856、0.852(P<0.05)。结论分期越高和有淋巴结转移的肺癌均会导致SIRT3低表达和ATF2高表达,且SIRT3低表达、ATF2高表达还会加大肺癌化疗的不良预后风险,SIRT3、ATF2与肺癌化疗预后存在一定关联,两者联合有利于评估和预测肺癌的病情及其预后情况。

Objective To analyze the predictive value of changes in the expression of deacetylase 3(SIRT3)and activated transcription factor 2(ATF2)in patients with lung cancer during perioperative chemotherapy.Methods A total of 80 patients with lung cancer who underwent chemotherapy in Hanzhong Central Hospital from January 2018 to January 2021 were retrospectively selected as the study subjects.The expression of SIRT3 and ATF2 was detected by immunohistochemistry before and after chemotherapy.The relationship between the high and low expression of SIRT3 and ATF2 and the pathological characteristics of lung cancer was analyzed.The expression levels of SIRT3 and ATF2 in patients with different prognosis were detected by real-time fluorescence quantitative PCR(qRT-PCR).Multivariate Logistic model was established to analyze the independent risk factors affecting the prognosis of lung cancer chemotherapy,and the predictive value of SIRT3 and ATF2 in the prognosis of lung cancer chemotherapy was analyzed.Results The high expression and low expression rates of SIRT3 in 80 cases of lung cancer were 42.50%and 57.50%,respectively,and the high expression and low expression rates of ATF2 were 55.00%and 45.00%,respectively.There were no statistically significant differences in the high and low expression rates of SIRT3 and ATF2 in lung cancer(P>0.05).The proportions of patients with high expression of SIRT3,TNM>stageⅢ,and lymph node metastasis were 9.09%,25.00%,which were significantly lower than those of patients with low expression of SIRT3(90.91%,75.00%),and the differences were statistically significant(P<0.05);the proportions of lung cancer patients with high expression of ATF2,TNM>stage III,and lymph node metastasis were 95.45%,71.43%,which were significantly higher than those of patients with low expression of ATF2(4.55%,28.57%),and the differences were statistically significant(P<0.05).Among the 80 lung cancer patients,there were 52 cases in the group with good prognosis and 28 cases in the group with poor prognosis.After chemotherapy,the expression level of SIRT3 mRNA in patients with poor prognosis group was 1.74±0.13,which was higher than that in patients with good prognosis group(1.41±0.11),while the expression level of ATF2 mRNA was 0.25±0.04,which was lower than that in patients with good prognosis group(0.34±0.04),and the differences were statistically significant(P<0.05).The results of multivariate logistic analysis showed that TNM staging,lymph node metastasis,SIRT3,and ATF2 were independent risk factors affecting the prognosis of lung cancer chemotherapy(P<0.05).The area under the curve(AUC)of SIRT3,ATF2,and SIRT3+ATF2 in predicting the prognosis of lung cancer chemotherapy were all greater than 0.80,and it was found that the combined prediction of SIRT3+ATF2 for AUC was 0.896,which was greater than the 0.856 and 0.852 of SIRT3 and ATF2(P<0.05).Conclusion Higher stage and lung cancer with lymph node metastasis will lead to low SIRT 3 expression and high ATF 2 expression,and low SIRT 3 expression and high ATF 2 expression will also increase the risk of poor prognosis of lung cancer chemotherapy,SIRT 3 and ATF 2 have a certain correlation with the prognosis of lung cancer chemotherapy,the combination of both is beneficial to evaluate and predict the condition of lung cancer and its prognosis.