免疫浸润相关基因mRNA在宫颈癌与宫颈癌前病变中的表达及其与预后的关系

mRNA Expression of Immune Infiltration-related Genes in Cervical Cancer and Precancerous Lesions and Their Relationship with Prognosis

目的探讨免疫浸润相关基因mRNA在宫颈癌与宫颈癌前病变中的表达水平及其与预后的关系。方法选取延安大学附属医院2017年1月至2019年1月宫颈癌患者74例作为宫颈癌变组,宫颈癌前病变患者74例作为宫颈癌前病变组,另选取同期因子宫肌瘤行子宫切除术患者74例作为宫颈正常组,比较3组免疫浸润相关基因[人类白细胞抗原G(HLA-G)、叉状头螺旋转录因子3(FOXP3)、T细胞免疫球蛋白粘连蛋白-3(TIM-3)]、恶性生物学行为相关基因[侵袭基因p21-活化的激酶6(PAK-6)、zeste 2多梳抑制复合物2亚基增强子(EZH2)、增殖基因血管生成素样蛋白4(ANGPTL4)、同源盒基因B7(HOXB7)]的mRNA相对表达量,分析免疫浸润相关基因与宫颈癌发生及宫颈癌恶性生物学行为的关系,并统计对比不同免疫浸润相关基因表达水平患者3年生存率。结果HLA-G、FOXP3、TIM-3 mRNA相对表达量为宫颈癌变组>宫颈癌前病变组>宫颈正常组(P<0.05);不同临床分期、分化程度,以及有无淋巴结转移、有无脉管浸润患者的HLA-G、FOXP3、TIM-3、PAK-6、EZH2、ANGPTL4、HOXB7 mRNA相对表达量差异有统计学意义(P<0.05);HLA-G、FOXP3、TIM-3的mRNA高表达患者宫颈癌前病变进展至宫颈癌的风险分别是低表达患者的3.005倍、4.654倍、3.343倍;宫颈癌患者HLA-G、FOXP3、TIM-3 mRNA与侵袭相关基因PAK-6、EZH2 mRNA、增殖相关基因ANGPTL4、HOXB7的mRNA表达呈正相关(P<0.05);随访3年,失访2例,72例宫颈癌患者3年生存率为68.06%(49/72),HLA-G、FOXP3、TIM-3的mRNA高表达患者3年生存率均低于低表达患者(P<0.05)。结论免疫浸润相关基因HLA-G、FOXP3、TIM-3的mRNA在宫颈癌与宫颈癌前病变中呈上调表达,会显著增加宫颈癌发病风险,且与宫颈癌恶性生物学行为密切相关,还可能对生存预后产生重要影响。

Objective To investigate the mRNA expression levels of immune infiltration-related genes in cervical cancer and cervical precancerous lesions and the relationship with prognosis.Methods A total of 74 patients with cervical cancer(cervical cancer group),74 patients with cervical precancerous lesions(cervical pre-cancer lesions group),and another 74 patients who underwent hysterectomy for uterine fibroids(normal cervix group)in Affiliated Hospital of Yan’an University from January 2017 to January 2019 were selected.The mRNA expression levels of the immune infiltration-related genes[human leukocyte antigen G(HLA-G),forked-head helix transcription factor 3(FOXP3),T cell immunoglobulin and mucin domain 3(TIM-3)],and the malignant biological behavior related genes[invasive gene P21-activated kinase 6(PAK-6),zeste 2 multiple comb inhibitory complex 2 subunit enhancer(EZH2),proliferative gene angiopoietin-like protein 4(ANGPTL4),homologous box gene B7(HOXB7)]were compared among the above three groups.The relationship between the expression levels of the immune infiltration-related genes and the carcinogenesis and malignancy of cervical cancer were analyzed.The 3-year survival rate of patients with high or low mRNA expression levels of immune infiltration-related genes were compared.Results The relative mRNA expression levels of HLA-G,FOXP3 and TIM-3 in the cervical cancer group were the highest,and were lower in the cervical pre-cancer lesions group,the relative mRNA expression levels of the three genes were lowest in the normal cervix group(all P<0.05).Statistical significant differences were found in the relative mRNA expression levels of HLA-G,FOXP3,TIM-3,PAK-6,EZH2,ANGPTL4 and HOXB7 in patients with different clinical stages,degrees of differentiation,and presence or absence of lymph node metastasis and vascular infiltration(P<0.05).The risks of progression of cervical pre-cancer lesions to cervical cancer in patients with high mRNA expression levels of HLA-G,FOXP3 and TIM-3 were 3.005,4.654 and 3.343 times higher than those in patients with low expression levels respectively.The mRNA expression levels of HLA-G,FOXP3 and TIM-3 were positively correlated with the mRNA expression levels of PAK-6,EZH2,ANGPTL4 and HOXB7(P<0.05).In 3 years of follow-up,2 cases of cervical cancer were lost,the 3-year survival rate of the cervical cancer patients was 68.06%(49/72),and the 3-year survival rate of patients with high mRNA expression levels of HLA-G,FOXP3 and TIM-3 was lower than that of patients with low expression levels(P<0.05).Conclusion The mRNA of Immune infiltration-related genes HLA-G,FOXP3 and TIM-3 are upregulated in cervical cancer and cervical pre-cancer lesions,which significantly increases the risk of cervical cancer carcinogenesis and malignancy,it also have an important impact on the survival prognosis of cervical cancer patients.