摘要
目的探讨晚期宫颈癌患者的缺氧诱导因子-1α(hypoxia inducible factor-1,HIF-1α)、缺氧诱导因子-2α(hypoxia inducible factor-2,HIF-2α)以及核苷酸切除修复交叉互补-1(excision repair cross-complementing-1,ERCC-1)蛋白检测的临床意义。方法选取2014年8月2016年2月收治的晚期宫颈癌患者30例为观察组,另选取同时间段收治的宫颈良性病变患者30例为对照组。采用RT-PCR以及免疫组化法检测2组患者的病变组织中HIF-1α、HIF-2α的mRNA和蛋白水平,分析HIF-1α、HIF-2α与疾病发生发展的相关性。并根据观察组患者外周血基ERCC-1因表达的不同,将观察组患者分为C组和T组,给予观察组患者顺铂新辅助化疗,观察化疗后C组和T组患者的疗效指标,分析新辅助化疗治疗效果与ERCC-1表达的相关性。结果HIF-1αmRNA、HIF-2αmRNA在观察组和对照组患者的组织标本中均有表达,组间比较差异有统计学意义(P<0.05);观察组HIF-1αmRNA、HIF-2αmRNA的表达量分别为(9.12±0.64)、(8.98±0.77),对照组为(7.13±0.33)、(7.02±0.15),2组比较差异有统计学意义(P<0.05)。观察组患者的HIF-1α蛋白表达阳性率为63.33%,对照组为16.67%,差异有统计学意义(P<0.05);观察组患者的HIF-2α蛋白表达阳性率为70.00%,对照组为13.33%,差异有统计学意义(P<0.05)。ERCC-1分型为C/C型的患者接受新辅助化疗后,近期疗效总有效率明显高于T/T型(P<0.05),中位生存期、中位进展时间和2年生存率也都明显优于T/T型(P<0.05),但两种分型在治疗期间的不良反应发生率差异无统计学意义(P>0.05)。Spearman或Pearson相关性分析显示:HIF-1α、HIF-2α与患者是否存在贫血有明显相关性(P<0.05),而ERCC-1分型与患者的化疗后中位PFS和中位TTP具有明显相关性(P<0.05)。结论在宫颈癌的发生和发展中,HIF-1α、HIF-2α可能具有一定的促进作用;新辅助化疗对ERCC-1分型为C/C型的患者的疗效明显优于T/T型患者,临床工作中,可将ERCC-1分型作为选择治疗方法的参考指标。
Objective To investigate the clinical significance of detection of hypoxia inducible factor-1(HIF-1α),hypoxia inducible factor-2(HIF-2α)and excision repair cross-complementating 1(ERCC-1)in patients with advanced cervical cancer.Methods Thirty patients with advanced cervical cancer who were admitted and treated in our hospital from August 2014 to February 2016 were enrolled as observation group,and 30 patients with benign cervical lesions who were treated at the same period were enrolled as control group.The mRNA and protein levels of HIF-1αand HIF-2αin the lesions were detected by RT-PCR and immunohistochemistry.The correlation between HIF-1α,HIF-2αand the occurrence and development of the disease was analyzed.According to the different expression levels of ERCC-1 in peripheral blood,the patients in observation group were redivided into group C and group T,and given neoadjuvant chemotherapy with cisplatin.The therapeutic indexes of patients in group C and group T were observed after chemotherapy,and the correlation between the effect of neoadjuvant chemotherapy and the expression of ERCC-1 was analyzed.Results Both HIF-1αmRNA and HIF-2αmRNA were expressed in the tissue samples in observation group and the control group,and the difference between the two groups was statistically significant(P<0.05).The expression levels of HIF-1αmRNA and HIF-2αmRNA were(9.12±0.64)and(8.98±0.77),respectively in observation group,which were(7.13±0.33)and(7.02±0.15),respectively in control group,and there were significant differences between the two groups(P<0.05).The positive expression rate of HIF-1αprotein was 63.33%and 16.67%in observation group and control group,respectively,and the difference was statistically significant(P<0.05).The positive expression rate of HIF-2αprotein was 70.00%and 13.33%in observation group and control group,respectively,and the difference was statistically significant(P<0.05).After neoadjuvant chemotherapy,the total effective rate of short-term efficacy in patients with C/C genotype of ERCC-1 was significantly higher than that in patients with T/T genotype(P<0.05).In addition,median survival time,median progression time and 2-year survival rate in patients with C/C genotype of ERCC-1 were significantly better than those of patients with T/T genotype(P<0.05),but there was no significant difference in the incidence of adverse reactions between the patients with two different genotypes during treatment(P>0.05).Spearman or Pearson correlation analysis showed that HIF-1αand HIF-2αwere significantly associated with anemia in patients(P<0.05),while ERCC-1 classification was significantly correlated with median PFS and median TTP after chemotherapy(P<0.05).Conclusion HIF-1αand HIF-2αmay play a certain role in promoting the occurrence and development of cervical cancer.Neoadjuvant chemotherapy has a better therapeutic effect in patients with C/C genotype of ERCC-1 than in those with T/T genotype.In clinical practice,ERCC-1 classification can be used as a reference index for the selection of treatment methods.
作者
袁小庆
邢益祥
康敏
YUAN Xiaoqing;XING Yixiang;KANG Min(People’s Hospital of Tongling City,Anhui,Tongling 244000,China)
出处
《河北医药》
CAS
2020年第5期673-676,680,共5页
Hebei Medical Journal
基金
安徽省自然科学青年基金项目(编号:1408085QH176)。
