宫颈癌组织中PD-1、HIF-1α、TAM表达变化及相关性研究

Expressions of PD-1,HIF-1α,and TAM in cervical cancer and their correlation with HPV

目的探讨宫颈癌组织中程序性死亡受体1(PD-1)、缺氧诱导因子(HIF)-1α、肿瘤相关的巨噬细胞(TAM)的表达变化以及相关性研究。方法采用免疫组织化学SP法检测PD-1、HIF-1α、TAM在正常宫颈组织24例、宫颈上皮内瘤变(CIN)组织30例、宫颈鳞状细胞癌组织42例中的表达情况,并分析其表达的相关性。结果PD-1主要表达于宫颈癌组织中,在正常宫颈组织中不表达,PD-1和HIF-1α在宫颈癌组织中的阳性表达率明显高于CIN组织(χ^2分别=38.04、19.56,P均<0.05),也明显高于正常宫颈组织(P<0.05)。TAM在CIN组织中的表达明显高于正常宫颈组织和宫颈癌组织(χ^2分别=30.59、12.32,P均<0.05)。PD-1、HIF-1α、TAM的阳性表达在宫颈癌患者不同分化程度、FIGO分期和淋巴结转移之间比较,差异均有统计学意义(χ^2分别=8.23、3.83、11.144、11.86、15.97、18.19、18.56、17.40、4.24,P均<0.05),在宫颈癌患者不同年龄、肿瘤直径之间比较,差异均无统计学意义(χ^2分别=0.08、0.46、0.76、0.00、0.35、0.02,P均>0.05)。根据HR-HPV核酸定量拷贝数分为四组:低载量组(10~4~10~5拷贝/ml),中载量组(10~5~10~6拷贝/ml),高载量组(10~6~10~7拷贝/ml)和超高载量组(>10~7拷贝/ml)。四组阳性率分别为7.14%(3/42)、11.91%(5/42)、26.19%(11/42)、47.62%(20/42)。PD-1、HIF-1α、TAM与HPV表达呈正相关(r分别=0.89、0.88、0.90,P均<0.05)。结论子宫颈癌组织中PD-1、HIF-1α、TAM呈高表达,并且其表达与肿瘤的发生和发展密切相关,阻断或抑制PD-1、HIF-1α、TAM的表达可能成为治疗宫颈癌的新方法。

Objective To investigate the expressions of programmed death receptor-1(PD-1),hypoxia inducible factor(HIF)-1αand tumor associated macrophages(TAM)in cervical cancer,and to explore the correlation with HPV.Methods The expressions of PD-1,HIF-1αand TAM in 24 cases of normal cervical tissue,30 cases of CIN(cervical intraepithelial neoplasia)and 42 cases of cervical squamous cell carcinoma were detected by immunohistochemical SP method,and their correlation with HPV was analyzed.Results PD-1 was mainly expressed in cervical cancer tissues,but not in normal cervical tissues.The expressions of PD-1 and HIF-1αin cervical cancer tissues were significantly higher than that in CIN(χ^2=38.04,19.56,P<0.05)and normal cervical tissues(P<0.05).The expression of TAM in CIN tissue was significantly higher than that in normal cervical tissue and cervical cancer tissue(χ^2=30.59,12.32,P<0.05).The differences in PD-1,HIF-1αand TAM among different differentiation degree,FIGO stage and lymph node metastasis were statistically significant(χ^2=8.23,3.83,11.144,11.86,15.97,18.19,18.56,17.40,4.24,P<0.05).The differences in PD-1,HIF-1αand TAM among different age,tumor diameter,and tissue type were not statistically significant(χ^2=0.08,0.46,0.76,0.00,0.35,0.02,P>0.05).According to the quantitative copy number of HR-HPV nucleic acid,they were divided into four groups:low load group(10~4-10~5 copies/ml),medium load group(10~5-10~6 copies/ml),high load group(10~6-10~7 copies/ml)and ultra-high load group(>10~7 copies/ml).The positive rates of the four groups were 7.14%(3/42),11.91%(5/42),26.19%(11/42)and 47.62%(20/42),respectively.The PD-1,HIF-1αand TAM were positively correlated with HPV expression(r=0.89,0.88,0.90,P<0.05).Conclusion The PD-1,HIF-1α,and TAM are highly expressed in human cervical carcinoma,and their expression are closely related to the occurrence and development of tumor.Blocking or inhibiting the expressions of PD-1,HIF-1αand TAM maybe a new method for the treatment of cervical cancer.