SMAD7、SMAD9与肺腺癌患者预后及免疫浸润的相关性分析  

Correlation analysis of SMAD7,SMAD9 with prognosis and immune infiltration in patients with lung adenocarcinoma

作　　者：李晓武 张有为[1] 冯玉 韩亮[1] 袁媛[1] LI Xiaowu;ZHANG Youwei;FENG Yu;HAN Liang;YUAN Yuan(Medical Oncology,Xuzhou Central Hospital,Xuzhou Jiangsu 221000,China)

机构地区：[1]徐州市中心医院肿瘤内科,江苏徐州221000

出　　处：《新疆医科大学学报》2023年第10期1319-1325,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金面上项目(82172892)。

摘　　要：目的 本研究旨在探讨SMAD7、SMAD9在肺腺癌中的预后价值及其与免疫浸润的相关性。方法 借助GEPIA数据库预测SMAD家族成员在肺腺癌组织与癌旁组织中的表达水平,筛选差异表达的成员作为关键基因纳入研究。分析关键基因对肺腺癌患者预后的影响,GEPIA与TIMER数据库分析关键基因与免疫浸润的相关性。收集108例手术切除的肺腺癌患者组织,使用qRT-PCR验证关键基因在组织内的表达水平。分析关键基因对患者5年生存率的影响及影响生存率的独立预测因素。结果 GEPIA数据库预测结果显示,相对于正常组织样本,SMAD7、SMAD9在癌组织样本中的表达降低(P均<0.05)。GEPIA数据库预测结果显示SMAD7、SMAD9低表达水平患者总生存率低于SMAD7、SMAD9高表达水平患者(P均<0.05)。TIMER网站预测结果显示SMAD7与B细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞、树突状细胞水平均呈正相关(P均<0.05),SMAD9与B细胞、CD4^(+)T细胞、巨噬细胞水平呈正相关(P均<0.05)。GEPIA网站显示SMAD7与CD115、CD86、CD68、CCL2、IRF5呈正相关(P均<0.05),SMAD9与CCL2、IRF5呈正相关(P均<0.05)。相对于癌旁组织中SMAD7(1.00±0.27)、SMAD9(1.00±0.31)的表达,癌组织中SMAD7(0.76±0.24)、SMAD9(0.81±0.22)的表达降低(P均<0.05)。SMAD7、SMAD9低表达患者的5年总生存率低于高表达患者(P均<0.05)。Cox分析结果显示,淋巴结转移、T3+T4分期、组织学Ⅲ级与SMAD7、SMAD9水平是影响患者总生存时间的独立风险因素(P均<0.05)。结论 SMAD7、SMAD9是预测肺腺癌不良预后的潜在生物分子,与免疫浸润水平相关,可能参与免疫细胞调节。Objective To investigate the prognostic value of SMAD7 and SMAD9 in lung adenocarcinoma and their correlation with immune infiltration.Methods The expression levels of SMAD family members in lung adenocarcinoma tissues and adjacent tissues were predicted by GEPIA database,and the differentially expressed members were selected as key genes to be included in the study,and the influence of key genes on the prognosis of lung adenocarcinoma patients was further analyzed.GEPIA and TIMER databas-es were used to analyze the correlation between key genes and immune infiltration.Tissues of 108 patients with lung adenocarcinoma were collected and qRT-PCR was used to verify the expression levels of key genes in the tissues.The influence of key genes on 5-year survival rate and independent predictors of sur-vival rate were analyzed.Results The prediction results of GEPIA database showed that compared with normal tissue samples,the expressions of SMAD7 and SMAD9 in cancer tissue samples were decreased(P<0.05).The prediction results of GEPIA database showed that the overall survival rate of the patients with low expression level of SMAD7 and SMAD9 was lower than that of the patients with high expression level of SMAD7 and SMAD9(P<0.05).The prediction results of Timer website showed that SMAD7 was positively correlated with the levels of B cells,CD4^(+)T cells,macrophages,neutrophils and dendritic cells(all P<0.05),and SMAD9 was positively correlated with the levels of B cells,CD4^(+)T cells and macrophages(all P<0.05).The GEPIA website showed that SMAD7 was positively correlated with CD115,CD86,CD68,CCL2 and IRF5(all P<0.05),and SMAD9 was positively correlated with CCL2 and IRF5(all P<0.05).Compared with the expressions of SMAD7(1.00±0.27)and SMAD9(1.00±0.31)in adjacent tissues,the expressions of SMAD7(0.76±0.24)and SMAD9(0.81±0.22)in cancer tissues were decreased(P<0.05).The 5-year overall survival rate of the patients with low expression of SMAD7 and SMAD9 was lower than that of the patients with high expression(P<0.05).C

关 键 词：肺腺癌 SMAD家族 SMAD7 SMAD9 免疫浸润 

分 类 号：R734.2[医药卫生—肿瘤]