摘要
目的宫颈鳞癌中高表达的己糖激酶2(HK2)和丙酮酸激酶2(PKM2)与放射治疗抵抗的相关性尚不清楚。该实验研究HK2和PKM2的表达对放射治疗抵抗及预后的意义。方法回顾性分析132例在中南大学湘雅医院肿瘤放疗科和湖南省肿瘤医院接受放射治疗的局部进展期宫颈鳞癌(LACSCC)患者的临床资料。其中放射治疗敏感患者85例,放射治疗抵抗患者47例。采用免疫组织化学法检测HK2及PKM2表达。结果放射治疗抵抗组和放射治疗敏感组的HK2高表达分别为80.9%和45.9%,差异有统计学意义(P=0.000);放射治疗抵抗组和放射治疗敏感组的PKM2高表达分别为87.2%和57.6%,差异有统计学意义(P=0.000)。根据患者的临床资料放射治疗抵抗组分为3个亚组:放射治疗未控制组、局部复发组及远处转移组。3个亚组的HK2和PKM2高表达与放射治疗敏感组比较,差异有统计学意义。HK2低表达组和高表达组的5年无进展生存率分别为80.8%和56.5%,差异有统计学意义(P=0.000)。PKM2低表达组和高表达组的5年无进展生存率分别为80.4%和60.5%,差异有统计学意义(P=0.008)。单因素分析表明,HK2、PKM2、国际妇产科协会(FIGO)分期及肿瘤大小为宫颈鳞癌无进展生存期(PFS)的独立预后指标[HR_(HK2)=3.454,(95%CI1:1.764,6.765),P_(HK2)=0.000;HR_(PKM2)=3.278,(95%CI2:1.535,7.000),P_(PKM2)=0.002;HR_(FIGO分期)=2.610,(95%CI3:1.453,4.689),P_(FIGO)分期=0.001;HR_(肿瘤大小)=3.366,(95%CI4:1.885,6.012),P_(肿瘤大小)=0.000]。结论高表达HK2和PKM2与放射治疗抵抗性密切相关,是LACSCC预后不良因素之一。HK2和PKM2有望成为预测放射治疗疗效和指导治疗的理想指标,值得深入研究。
[Objective] To investigate the association of high expressions of hexokinase 2 （HK2） and pyruvate kinase isozyme type M2 （PKM2） with radiation resistance in locally advanced cervical squamous cell carcinoma （LACSCC） and its significance. [Methods] In this study 132 female patients who received radio- therapy for LACSCC were retrospectively analyzed, including 85 radiation-sensitive cases and 47 radiation-re sistant cases. The expressions of HK2 and PKM2 were examined by immunohistochemistry. [Results] High expression rate of HK2 in the radiation-resistant and radiation-sensitive groups was 80.9% and 45.9%, respectively, and the difference was statistically significant （P = 0.000）. The high expression rate of PKM2 was 87.2% and 57.6% in the radiation-resistant and radiation-sensitive groups respectively, and the difference was statistically significant （P= 0.000）. The 5-year progress-free survival （PFS） rate in the patients with low and high expression of HK2 was 80.8% and 56.5% respectively with statistical difference （P= 0.000）. The 5-year progress-free survival rate in the patients with low and high expression of PKM2 was 80.4% and 60.5% re- spectively, and the difference was statistically significant （P= 0.008）. Univariate analyses showed that HK2 [HR = 3.454, （95%CI： 1.764, 6.765）, P= 0.000], PKM2 [HR = 3.278, （95%CI： 1.535, 7.000）, P= 0.002], FIGO stage [HR = 2.610, （95%CI： 1.453, 4.689）, P= 0.001] and tumor diameter [HR = 3.366, （95%CI： 1.885, 6.012）, P= 0.000] were the prognostic predictors of PFS in the patients with cervical SCC. [Conclusions] Over-expres- sions of HK2 and PKM2 indicate LACSCC with radioresistance. Either of them can be considered as an inde- pendent poor prognostic biomarker for cervical squamous carcinoma, may become the ideal molecular therapeu- tic target with good clinical application prospects and is worthy of exploring.
出处
《中国现代医学杂志》
CAS
北大核心
2015年第32期1-8,共8页
China Journal of Modern Medicine
基金
国家自然科学基金(No:81372792)
湖南省科技厅重点项目(No:2013sk2019)
湖南省自然科学基金(No:2015JJ4055)
关键词
局部进展期宫颈鳞癌
放射治疗抵抗
糖酵解
己糖激酶2
丙酮酸激酶2
免疫组织化学
locally advanced cervical squamous cell carcinoma
radiation resistance
glycolysis
hexoki-nase 2
pyruvate kinase isozyme type M2
immunohistochemistry
