摘要
目的探讨肺腺癌组织Alk B同源蛋白(ALKBH)2、ALKBH4表达与临床病理特征和预后的关系。方法本研究为前瞻性队列研究,采用非随机抽样的方法选取2018年1月至2020年1月于临沂市肿瘤医院接受肿瘤切除手术的135例肺腺癌患者为研究对象。免疫组织化学法检测患者术中采集的肺腺癌组织和癌旁组织(距离癌组织>3 cm)ALKBH2、ALKBH4表达。根据肺腺癌组织中ALKBH2、ALKBH4的表达情况将患者分为ALKBH2阳性表达组(77例)与ALKBH2阴性表达组(58例);ALKBH4阳性表达组(61例)与ALKBH4阴性表达组(74例)。分析肺腺癌组织ALKBH2、ALKBH4表达与肺腺癌患者临床病理特征(包括性别、年龄、吸烟史、肿瘤部位、基因突变情况、病理分型、胸膜脉管侵犯、气腔播散和脉管癌栓情况、手术切除范围、肿瘤长径、分化程度、TNM分期、淋巴结转移情况和术后有无接受化疗)的关系。肺腺癌患者出院后通过电话随访的方式每6个月随访1次,随访3年,随访截至2023年1月或患者死亡,统计3年总生存率。Kaplan-Meier法绘制生存曲线,并采用Log-rank检验比较肺腺癌组织中不同ALKBH2、ALKBH4表达情况患者的生存曲线。采用单因素和多因素Cox回归分析肺腺癌患者预后的影响因素。结果135例肺腺癌患者中男78例,女57例;年龄(60.28±7.43)岁,年龄范围27~74岁。肺腺癌组织ALKBH2、ALKBH4阳性表达率均高于癌旁组织[57.04%(77/135)比25.19%(34/135),45.19%(61/135)比19.26%(26/135),均P<0.001]。有胸膜脉管侵犯、有气腔播散、有脉管癌栓、分化程度为低分化、TNM分期为Ⅲ期、有淋巴结转移的肺腺癌患者的肺腺癌组织ALKBH2、ALKBH4阳性表达率均高于无胸膜脉管侵犯、无气腔播散、无脉管癌栓、分化程度为中高分化、TNM分期为Ⅰ~Ⅱ期、无淋巴结转移患者(ALKBH2阳性表达率比较χ^(2)值分别为5.51、6.54、6.82、5.36、6.53和8.22,ALKBH4阳性表达率比较χ^(2)值分别为5.57、6.17、6.07、5.88、7.20和8.60,均P<0.05)。135例肺腺癌患者随访3年,失访6例,死亡62例,3年总生存率为54.07%(73/135)。Log-rank检验结果显示,ALKBH2阴性表达组患者的生存状态优于ALKBH2阳性表达组(χ^(2)=11.84,P=0.001),ALKBH4阴性表达组患者的生存状态优于ALKBH4阳性表达组(χ^(2)=10.17,P=0.001)。多因素Cox回归分析显示,病理分型为微乳头型(相比贴壁型HR=1.205,95%CI:1.054~1.376)、有胸膜脉管侵犯(HR=3.587,95%CI:1.110~11.589)、有气腔播散(HR=3.357,95%CI:1.068~10.556)、有脉管癌栓(HR=3.671,95%CI:1.171~11.511)、低分化(HR=3.714,95%CI:1.068~10.556)、TNM分期为Ⅲ期(HR=4.711,95%CI:1.165~19.047)、有淋巴结转移(HR=5.136,95%CI:1.069~24.673)、ALKBH2表达阳性(HR=4.218,95%CI:1.149~15.482)、ALKBH4表达阳性(HR=3.713,95%CI:1.055~13.071)为肺腺癌患者死亡的独立危险因素(均P<0.05)。结论肺腺癌组织ALKBH2、ALKBH4表达上调,与病理分型、胸膜脉管侵犯、气腔播散、脉管癌栓、分化程度、TNM分期、淋巴结转移和不良预后有关。
Objective To investigate the correlation of the expressions of Alk B homologue(ALKBH)2 and ALKBH4 in lung adenocarcinoma tissues with clinical and pathological features and prognosis.Methods This was a prospective cohort study.Totally 135 lung adenocarcinoma patients who underwent tumor resection surgery in Linyi Cancer Hospital from January 2018 to January 2020 were enrolled using a non-random sampling method.Immunohistochemical method was used to detect the expressions of ALKBH2 and ALKBH4 in surgically collected lung adenocarcinoma tissues and adjacent tissues(distance from cancer tissue>3 cm).According to the expressions of ALKBH2 and ALKBH4 in lung adenocarcinoma tissue,patients were divided into ALKBH2-positive expression group(77 cases),ALKBH2-negative expression group(58 cases),ALKBH4-positive expression group(61 cases),and ALKBH4-negative expression group(74 cases).The correlation of the expressions of ALKBH2 and ALKBH4 in lung adenocarcinoma tissues with the clinical and pathological characteristics(including gender,age,smoking history,tumor location,gene mutation status,pathological classification,pleural vascular invasion,air cavity dissemination and vascular cancer thrombus situation,surgical resection range,maximum tumor diameter,degree of differentiation,tumor-node-metastasis(TNM)staging,lymph node metastasis,and postoperative chemotherapy)of lung adenocarcinomas was analyzed.After discharge,lung adenocarcinoma patients were followed up every 6 months via telephone contact for a period of 3 years,until the end point in January 2023 or death.The overall 3-year survival rate was calculated.Kaplan-Meier method was used to draw survival curves,followed by Log-rank test to compare the survival curves of patients with different ALKBH2 and ALKBH4 expression levels in lung adenocarcinoma tissues.Univariate and multivariate Cox regression analyses of prognostic factors in lung adenocarcinoma patients were performed.Results Among 135 patients with lung adenocarcinomas,there were 78 males and 57 females with the mean age of 60.28±7.43(27-74)years old.The positive expression rates of ALKBH2 and ALKBH4 in lung adenocarcinoma tissues were significantly higher than those of adjacent tissues(57.04%[77/135]vs 25.19%[34/135],45.19%[61/135]vs 19.26%[26/135],both P<0.001).In lung adenocarcinoma patients with pleural vascular invasion,air cavity dissemination,vascular cancer thrombus,poorly differentiated degree,TNM stagingⅢ,and lymph node metastasis,the positive expression rates of ALKBH2 and ALKBH4 in lung adenocarcinoma tissue were significantly higher than those of counterparts(χ^(2) in ALKBH2 positive expression rate:5.51,6.54,6.82,5.36,6.53 and 8.22 respectively;χ^(2) in ALKBH4 positive expression rates:5.57,6.17,6.07,5.88,7.20 and 8.60,respectively;all P<0.05).A total of 135 patients with lung adenocarcinomas were followed up for 3 years,with 6 cases of lost to follow-up and 62 deaths.The overall 3-year survival rate was 54.07%(73/135).The Log-rank test results showed that the survival status of patients in the ALKBH2-negative expression group was better than that of the ALKBH2-positive expression group(χ^(2)=11.84,P=0.001),and the survival status of patients in the ALKBH4-negative expression group was better than that of the ALKBH4-positive expression group(χ^(2)=10.17,P=0.001).Multivariate Cox regression analysis showed that the pathological classification of micropapillary type(HR=1.205,95%CI:1.054-1.376 vs adherent subtype),pleural vascular invasion(HR=3.587,95%CI:1.110-11.589),air cavity dissemination(HR=3.357,95%CI:1.068-10.556),vascular cancer thrombus(HR=3.671,95%CI:1.171-11.511),poorly differentiated(HR=3.714,95%CI:1.068-10.556),TNM stagingⅢ(HR=4.711,95%CI:1.165-19.047),lymph node metastasis(HR=5.136,95%CI:1.069-24.673),positive ALKBH2 expression(HR=4.218,95%CI:1.149-15.482),and positive ALKBH4 expression(HR=3.713,95%CI:1.055-13.071)were independent risk factors for mortality in lung adenocarcinoma patients(all P<0.05).Conclusions The upregulation of ALKBH2 and ALKBH4 in lung adenocarcinoma tissue is related to pathological classification,pleural vascular invasion,air cavity dissemination,vascular cancer thrombus,differentiation degree,TNM staging,lymph node metastasis,and poor prognosis.
作者
提运山
邢祥
阎勋会
Ti Yunshan;Xing Xiang;Yan Xunhui(Department of Thoracic Surgery,Linyi Cancer Hospital,Linyi 276000,China)
出处
《国际呼吸杂志》
2024年第5期529-536,共8页
International Journal of Respiration
基金
山东省医药卫生科技发展计划项目(201814031180)。
