肺腺癌组织中METTL3蛋白表达水平及其与18 F-FDG最大标准摄取值的相关性

METTL3 protein expression level in lung adenocarcinoma tissues and its correlation with maximum standardized uptake value of 18 F-FDG

目的探讨肺腺癌(LUAD)组织中甲基转移酶3(METTL3)蛋白表达水平及其与18 F-氟脱氧葡萄糖(18 F-FDG)最大标准摄取值(SUVmax)的相关性。方法回顾性分析2017年1月至2018年12月在该院进行肺部手术前接受18 F-FDG PET/CT扫描的所有LUAD患者资料,共收集89例LUAD患者的肿瘤组织标本及其相匹配的30例癌旁组织标本。采用免疫组织化学染色法检测LUAD组织中METTL3蛋白表达水平。对所有患者随访1年,并进行生存分析。采用Spearman相关对METTL3蛋白表达评分与PET/CT参数的相关性进行分析。结果TCGA数据库癌症基因组图谱数据显示,483例LUAD组织中METTL3 mRNA表达水平明显高于59例正常肺组织,差异有统计学意义(P<0.05)。89例LUAD组织中METTL3蛋白阳性表达率为52.81%(47/89),与相匹配的30例癌旁组织比较,LUAD组织中METTL3蛋白阳性表达率(56.67%)明显高于癌旁组织(16.67%),差异有统计学意义(P<0.05)。不同肿瘤最大径、肿瘤分化程度和淋巴结转移LUAD患者肿瘤组织METTL3蛋白表达情况比较,差异均有统计学意义(P<0.05)。与METTL3阴性组比较,METTL3阳性组SUVmax明显升高,差异有统计学意义(P<0.05)。Spearman相关分析结果显示,LUAD患者METTL3蛋白表达评分与SUVmax呈明显正相关(r=0.667,P<0.001)。SUVmax预测METTL3阳性表达的受试者工作特征曲线下面积为0.851(95%CI:0.773~0.928),对应的最佳截断值为10.55,灵敏度和特异度分别为83.0%和73.8%。随访期间,METTL3蛋白阳性组较阴性组中位总生存期更短,且总生存率更低,差异有统计学意义(χ^(2)=9.726,P=0.002)。结论LUAD组织中METTL3有望成为新的病理诊断和预后标志物。LUAD组织中METTL3蛋白表达评分与18 F-FDG SUVmax呈正相关,18 F-FDG SUVmax可能是反映METTL3蛋白表达评分的无创检测工具。

Objective To investigate the expression of methyltransferase 3(METTL3)protein in lung adenocarcinoma(LUAD)tissues and its correlation with the maximum standardized uptake value(SUVmax)of 18 F-fluorodeoxyglucose(18 F-FDG).Methods Retrospective analysis in January 2017 to December 2018 before it performs lung surgery for 18 F-FDG PET/CT scan of all LUAD patient data,a total of tumor tissue samples from 89 patients with LUAD and its matching in 30 cases of tissue adjacent to carcinoma specimens.The expression level of METTL3 protein in LUAD tissues was detected by immunohistochemical staining.All patients were then followed up for 1 year,and survival analysis was performed.Spearman correlation was used to evaluate the correlation between METTL3 protein expression score and PET/CT parameters.Results The Cancer genome Atlas data of TCGA database showed that the mRNA expression level of METTL3 in 483 LUAD tissues was significantly higher than that in 59 normal lung tissues,and the difference was statistically significant(P<0.05).The positive expression rate of METTL3 protein in 89 LUAD tissues was 52.81%(47/89).Compared with 30 matched para-cancerous tissues,the positive expression rate of METTL3 protein in LUAD tissues(56.67%)was significantly higher than that in para-cancerous tissues(16.67%),with statistical significance(P<0.05).Different tumor size,tumor differentiation degree and lymph node metastasis in patients with LUAD METTL3 protein expression in tumor tissues,the difference had statistical significance(P<0.05).Compared with METTL3 negative group,SUVmax in METTL3 protein positive group was significantly increased,and the difference was statistically significant(P<0.05).Spearman correlation analysis showed that METTL3 protein expression score in LUAD patients was significantly positively correlated with SUVmax(r=0.667,P<0.001).The area under the receiver operating characteristic curve of SUVmax for predicting METTL3 positive expression was 0.851(95%CI:0.773-0.928),the corresponding best cut-off value was 10.55,and the sensitivity and specificity were 83.0%and 73.8%respectively.During the follow-up period,the median overall survival time of METTL3 protein positive group was shorter than that of METTL3 protein negative group,and the overall survival rate was lower,the difference was statistically significant(χ^(2)=9.726,P=0.002).Conclusion LUAD tissue METTL3 protein is expected to be a new pathologic diagnostic and prognostic marker.The expression score of METTL3 protein in LUAD tissue was positively correlated with 18 F-FDG SUVmax,which may be a non-invasive monitoring tool reflecting METTL3 protein expression level.