ALDH2基因多态性与局部晚期食管鳞癌患者放化疗预后的关系分析  

Analysis of the relationship between ALDH2gene polymorphism and prognosis of patients with locally advanced esophageal squamous cell carcinoma treated with radiotherapy and chemotherapy

作　　者：田静 赵静 杨关丽 崔斌[3] 王娜 冯庆云 韩丹 TIAN Jing;ZHAO Jing;YANG Guanli;CUI Bin;WANG Na;FENG Qingyun;HAN Dan(Jinan Zhangqiu District People's Hospital Affiliated to Jining Medical College,Jinan250200,China;Department of Oncology,Tangdu Hospital,Fourth Military Medical University,Xi'an 710038,China;Department of Radiation Oncology,Shandong Cancer Hospital and Institute Affiliated to Shandong First Medical University,Shandong Provincial Key Laboratory of Radiation Oncology,Jinan250117,China)

机构地区：[1]济宁医学院附属济南市章丘区人民医院放疗科,山东济南250200 [2]济宁医学院附属济南市章丘区人民医院临床实验室,山东济南250200 [3]济宁医学院附属济南市章丘区人民医院化疗科,山东济南250200 [4]空军军医大学第二附属医院·唐都医院肿瘤科,陕西西安710038 [5]山东省肿瘤防治研究院(山东省肿瘤医院)放疗科,山东第一医科大学(山东省医学科学院),山东省放射肿瘤学重点实验室,山东济南250117

出　　处：《中华肿瘤防治杂志》2023年第9期538-545,共8页Chinese Journal of Cancer Prevention and Treatment

基　　金：济宁医学院教师科研扶持基金(JEFC2019FKJ008)。

摘　　要：目的分析乙醛脱氢酶2(ALDH2)在食管鳞癌中的表达状态,研究基因是否影响放化疗预后,为食管癌预后提供新的生物学指标。方法收集济南市章丘区人民医院2019-09-01-2021-10-30收治的接受同步放化疗治疗的不可切除局部晚期食管鳞癌患者80例,放疗采用调强适形放疗技术,化疗采用替吉奥联合铂类的方案,在治疗前抽取外周静脉血,采用sanger测序检测ALDH2基因多态性在食管鳞癌中的表达情况,采用生存分析方法分析无进展生存期(PFS)及总生存期(OS)影响因素,应用Kaplan-Meier行单因素分析,Cox回归行多因素分析。结果食管鳞癌患者ALDH2 rs671GG(野生型)和AG(杂合突变型)表达率分别为57.50%和42.50%;ADH1B rs1229984TT(野生型)、TC(杂合突变型)和CC(纯合突变型)表达率分别为40.00%、41.25%和18.75%;所有患者中位随访时间为22.8个月,中位PFS为13.5个月(95%CI为10.022~16.978),中位OS为22.8个月(95%CI为19.265~26.335)。单因素分析结果显示,影响PFS因素为T分期(P<0.001)、临床分期(P<0.001)、大体肿瘤体积(GTV,P=0.013)、ALDH2 rs671(P<0.001);影响OS因素为T分期(P=0.019)、临床分期(P=0.003)、肿瘤长度(P=0.011)、GTV(P=0.001)、肿瘤部位(P=0.049)。多因素分析显示,影响PFS的因素为临床分期(HR=4.170,95%CI为1.719~10.114,P=0.002)、GTV(HR=2.087,95%CI为1.069~4.073,P=0.031)、ALDH2 rs671(HR=2.746,95%CI为1.476~5.110,P=0.001);影响OS的因素为GTV,HR=2.834,95%CI为1.295~6.201,P=0.009。结论表达ALDH2 rs671 AG杂合突变基因型食管癌患者同步放化疗后复发风险高,其PFS与OS较短。ALDH2 rs671可作为接受同步放化疗治疗的不可切除局部晚期食管鳞癌患者预后标志物。Objective To analyze the expression of ALDH2in esophageal squamous cell carcinoma and to examine whether the gene affects the prognosis of patients who receive radiotherapy and chemotherapy.The study will provide new insights into the prognosis of esophageal carcinoma.Methods The study was conducted retrospectively on 80patients with unresectable locally advanced esophageal squamous cell carcinoma who received concurrent chemotherapy and radiotherapy in Jinan Zhangqiu District People's Hospital from September 1,2019to October 30,2021.Intensity modulated conformal radiotherapy and S-1combined with platinum were used in radiotherapy.The study used peripheral venous blood samples,which were drawn before the treatment began,to detect the expression of the ALDH2gene polymorphism in esophageal squamous cell carcinoma by using sanger sequencing.Survival analysis was used to analyze the factors that influence progression-free survival(PFS)and overall survival(OS).Univariate analysis was carried out by Kaplan-Meier and multivariate analysis by Cox regression.Results Two genotypes of ALDH2 rs671GG(wild type)and AG(heterozygous mutant),were expressed in patients with esophageal squamous cell carcinoma,and the rates were 57.50%and 42.50%.Three genotypes of ADH 1B rs1229984,respectively,TT(wild type),TC(heterozygous mutant)and CC(homozygous mutant),were expressed in patients with esophageal squamous cell carcinoma,and the rates were 40.00%,41.25%and 18.75%.The median follow-up time of all patients was 22.8months.The median PFS was 13.5months(95%CI:10.022-16.978),and the median OS was 14.5months(95%CI:19.265-26.335).Univariate analysis showed that T stage(P<0.001),clinical stage(P<0.001),gross tumor volume(GTV,P=0.013),and ALDH2 rs671(P<0.001)were the factors that influence PFS,while T stage(P=0.019),clinical stage(P=0.003),tumor length(P=0.011),GTV(P=0.001),and tumor location(P=0.049)were the factors that affected OS.Multivariate analysis showed that clinical stage(HR=4.170,95%CI:1.719-10.114,P=0.002),GTV(HR=2.087,95%CI:1.069

关 键 词：食管癌 乙醛脱氢酶2 同步放化疗 复发相关性 预后因素 

分 类 号：R735.1[医药卫生—肿瘤]