关键词: 宫颈癌, 宫颈癌前病变, 免疫浸润相关基因, 人类白细胞抗原 G, 叉状头螺旋转录因子 3, T 细胞免疫球蛋白粘连蛋白-3

Abstract: 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.

Key words: cervical cancer, cervical pre-cancer lesions, immune infiltration-related genes, human leukocyte antigen G, forked-head helix transcription factor 3, T-cell immunoglobulin adhesion protein-3