【摘要】 目的 分析乙醛脱氢酶基因(ALDH2)在肺腺癌(LUAD)中的表达对其预后的影响。方法 通过生物信息学，利用从TCGA数据库下载的肺腺癌RNA及临床资料，分析ALDH2基因在多种癌症中的表达情况，以及其在配对和非配对的肺腺癌样本中的表达，用免疫组化的方法验证ALDH2在肺腺癌中的表达。采用Kaplan-Meier方法和Cox回归分析ALDH2在LUAD中的临床特征关系及预后价值。用免疫棒棒糖图显示ALDH2与免疫浸润关系。结果 对于TCGA数据库下载的数据进行分析，可得到ALDH2在33种癌症中的表达情况，发现ALDH2在多形成性胶质细胞瘤、子宫内膜癌、乳腺浸润癌、肺腺癌、食管癌、胃和食管癌、混合肾癌、前列腺癌、胃癌、头颈鳞状细胞癌、肾透明细胞癌、肺鳞癌、肝细胞癌、肾母细胞瘤、黑色素瘤、膀胱尿路上皮癌、甲状腺癌、卵巢浆液性囊腺癌、子宫肉瘤、白血病、急性髓细胞样白血病、嗜铬细胞瘤和副神经节瘤、肾上腺皮质癌、肾嫌色细胞癌和胆管癌中低表达(P<0.001);在胶质瘤、脑低级别胶质瘤、肾乳头状细胞癌、结肠癌、结直肠癌和胰腺癌中表达上升(P<0.001);对肺腺癌及正常组织进行分析，发现ALDH2在LUAD中低表达(P<0.001);在肺腺癌中ALDH2的表达与患者的ALDH2的表达水平与肿瘤T分期(P=0.041)、淋巴结转移(P=0.009)、病理分级(P=0.037)、年龄(P=0.038)以及吸烟史(P=0.019)等临床特征显著相关；将肺腺癌患者分为高、低表达ALDH2两组，总体生存时间(OS)、疾病特异性生存期(DSS)、无进展间隔(PFI)、首次进展生存期(FP)、无复发生存期(RFS)具有显著差异；ROC分析ALDH2基因表达水平对预测患者有较好敏感性；ALDH2表达与免疫浸润的CD8+T细胞、T细胞、辅助性T细胞、CD56bright NK细胞、肥大细胞、嗜酸粒细胞和DC细胞显著相关；免疫组化显示LUAD中存在ADH2低表达。结论 ALDH2在肺腺癌中低表达，与其临床特征和患者预后情况具有相关性，可以作为肺腺癌患者预后良好的指标，且与免疫浸润相关。更多还原

【Abstract】 Objective To analyze the expression of aldehyde dehydrogenase 2(ALDH2) gene in lung adenocarcinoma(LUAD) and its impact on the prognosis.Methods Through bioinformatics analysis, the expression of ALDH2 gene in various cancers and paired and none-paired samples were analyzed by utilizing lung adenocarcinoma RNA and clinical data downloaded from the TCGA database.We verified the expression of ALDH2 in lung adenocarcinoma using immunohistochemistry.Kaplan-Meier method and Cox regression analysis were used to analyze the clinical characteristics and prognostic value of ALDH2 in LUAD.The relationship between ALDH2 and immune infiltration was displayed using an immune plot.Results Analysis of the data downloaded from the TCGA database reveals the expression of ALDH2 in 33 types of cancer.It was found that ALDH2 was down-regulated in glioblastoma multiforme, endometrial cancer, invasive breast cancer, lung adenocarcinoma, esophageal cancer, gastric and esophageal cancer, mixed renal cell carcinoma, prostate cancer, gastric cancer, head and neck squamous cell carcinoma, clear cell renal cell carcinoma, lung squamous cell carcinoma, hepatocellular carcinoma, Wilms tumor, melanoma, bladder urothelial carcinoma, thyroid cancer, ovarian mucinous cystadenocarcinoma, uterine sarcoma, leukemia, acute myeloid leukemia, pheochromocytoma and paraganglioma, adrenocortical carcinoma, renal chromophobe cell carcinoma, and cholangiocarcinoma(P<0.001).On the other hand, ALDH2 expression was up-regulated in gliomas, low-grade gliomas, papillary renal cell carcinoma, colon cancer, rectal cancer,and pancreatic cancer(P<0.001).In the analysis of lung adenocarcinoma and normal tissues,ALDH2 wasfound to be under-expressed in LUAD(P<0.001).Furthermore,ALDH2 expression in lung adenocarcinoma wassignificantly associated with clinical characteristics such as tumor T stage(P= 0.041),lymph node metastasis(P= 0.009),pathological grade(P= 0.037),age(P= 0.038),and smoking history(P= 0.019).Patients withlung adenocarcinoma were divided into high and low ALDH2 expression groups,and significant differences wereobserved in overall survival time(OS),disease-specific survival period(DSS),progression-free interval(PFI),first progression survival period( FP),and recurrence-free survival period( RFS). ROC analysis showed thatALDH2 gene expression levels had good sensitivity in predicting patient outcomes. ALDH2 expression was alsosignificantly associated with immune infiltrates such as CD8 + T cells,T cells,helper T cells,CD56bright NKcells,macrophages,eosinophils,and DC cells.Immunohistochemistry showed that ADH2 was under-expressed inLUAD.Conclusions ALDH2 is low expressed in lung adenocarcinoma and is significantly correlated with itsclinical features and patient prognosis.It can be served as a favorable prognostic indicator for lung adenocarcinomapatients and is associated with immune infiltration.更多还原