中晚期食管鳞癌组织SOX2和Twist1表达及对放化疗疗效影响

Expression of SOX2 and Twist1 in intermediate to advanced squamous esophageal carcinoma and their effect on the efficacy of radiotherapy and chemotherapy

目的研究SOX2和Twist1在中晚期食管鳞癌组织中表达情况及其与中晚期食管鳞癌同期放化疗疗效的关系。方法收集2014-04-06-2019-10-27郑州大学附属肿瘤医院收治的40例Ⅱ~Ⅲ期食管鳞癌患者肿瘤组织及相应的癌旁组织标本,采用免疫组化方法检测SOX2和Twist1表达水平;患者均行同期放化疗,治疗结束后4周进行近期疗效评价和远期生存随访。根据近期疗效分为敏感组和抗拒组。分析疗效与SOX2和Twist1的相关性。结果治疗结束后4周评价疗效,其中完全缓解、部分缓解和未缓解分别为13、15和12例。所有患者中位随访时间为17个月(95%CI为13.901~20.099),1年、3年和5年总生存率分别为62.5%、30.3%和25.3%。敏感组Twist1阳性表达率为3.57%(1/28),低于抗拒组的41.67%(5/12),χ^(2)=6.807,P=0.009;SOX2阳性表达率为32.14%(9/28),低于抗拒组的75%(9/12),χ^(2)=6.234,P=0.013。中晚期食管鳞癌组织中Twist1与SOX2表达不相关,r=0.124,P=0.446。生存分析显示:SOX2阴性表达组(评分<3分)生存率高于阳性表达组(评分≥3分),差异有统计学意义,χ^(2)=5.263,P=0.022;Twist1阴性表达组(评分<3分)生存率高于阳性表达组(评分≥3分),差异有统计学意义,χ^(2)=16.850,P<0.001。COX多因素回归分析显示,淋巴结转移情况(HR=6.092,95%CI为1.151~32.236,P=0.034)和SOX2表达(HR=13.106,95%CI为1.966~87.373,P=0.008)为患者独立预后因素。结论中晚期食管鳞癌组织中SOX2和Twist1均高表达,且与放疗敏感性和生存有关联,二者表达水平没有相关性。SOX2和Twist1可能是预测中晚期食管鳞癌放疗疗效新的分子标志物。

Objective To study the expression of SOX2 and Twist1 in the mid-to late-stage esophageal squamous carcinoma tissues and their relationship with the efficacy of concurrent radiotherapy and chemotherapy in the mid-to late-stage esophageal squamous carcinoma.Methods Tumour tissues and corresponding paraneoplastic tissue specimens were collected from 40 patients with stage Ⅱ-Ⅲ esophageal squamous carcinoma admitted to the Cancer Hospital of Zhengzhou University from April 6,2014 to October 27,2019,and SOX2 and Twist1 expression levels were detected by immunohistochemistry;patients were treated with concurrent radiotherapy and chemotherapy,and recent efficacy evaluation and long-term survival follow-up were performed at 4 weeks after the end of treatment.The patients were divided into sensitive and resistant groups according to the recent efficacy.The association between efficacy and SOX2 and Twist1 was analysed.Results The efficacy was evaluated at 4 weeks after the end of treatment,with 13,15 and 12 cases of CR,PR and NR,respectively.The median follow-up for all patients was 17 months(95% CI:13.901 to 20.099),with overall survival rates of62.5%,30.3% and 25.3% at 1,3 and 5 years,respectively.The positive expression rate of Twist1 was 3.57%(1/28)in the sensitive group,lower than that of 41.67%(5/12)in the resistant group,χ^(2)=6.807,P=0.009;the positiveexpression rate of SOX2 was 32.14%(9/28)in the sensitive group,lower than that of 75%(9/12)in the resistant group,χ^(2)=6.234,P=0.013.In tissues with intermediate to advanced esophageal squamous carcinoma Twist1 did not correlate with SOX2 expression,r=0.124,P=0.446.A survival analysis showed that the survival rate of SOX2 negative expression group(score<3)was higher than that of positive expression group(score≥3),the difference was statistically significant,χ^(2)=5.263,P=0.022;the survival rate of Twist1 negative expression group(score<3)was higher than that of positive expression group(score≥3),the difference was statistically significant,χ^(2)=16.85,P<0.001.A COX multifactorial regression analysis showed that lymph node metastasis status(HR=6.092,95%CI=1.151-32.236,P=0.034)and SOX2 expression(HR=13.106,95%CI=1.966-87.373,P=0.008)were independent prognostic factors for patients.Conclusions SOX2 and Twist1 were both highly expressed in tissues of intermediate to advanced esophageal squamous carcinoma and correlated with radiotherapy sensitivity and survival,while their expression levels did not necessarily correlate.SOX2 and Twist1 could potentially be new molecular markers for predicting the efficacy of radiotherapy in intermediate to advanced esophageal squamous carcinoma.