TAMs在HR-HPV诱发宫颈癌肿瘤微环境中的作用

摘要

目的 探讨肿瘤相关的巨噬细胞(TAMs)在高危型人乳头瘤病毒(HR-HPV)诱导的宫颈癌肿瘤微环境中的作用.方法 选择2014年12月至2017年6月浙江省台州医院的宫颈癌患者100例,设为宫颈癌组;选择同期入院治疗的宫颈癌前病变患者30例,设为癌前病变组;选择同期检查的健康体检人群30例,设为健康组.从上述三种标本中检测病毒蛋白E2、E6、E5、E7的表达.检测肿瘤组织及肿瘤旁组织检测CD14,CD163,CD206,CD68表达和T AM s表达;检测不同标本中差异基因表达,转录组学进行功能分析,利用R软件包分析.利用qRT-PCR法进一步检测临床标本中筛选出的M1/M2因子的表达.结果 三组病毒蛋白E2、E6、E5、E7和T AM s阳性率存在显著性差异(χ2值分别为6.392、5.091、7.392、4.883、5.691,均 P<0.05),宫颈癌组最高,癌前病变组次之,健康组最低.宫颈癌组宫颈癌组织中CD14、CD163、CD206、CD68阳性率均高于宫颈癌旁组织(χ2值分别为6.836、4.981、5.382、6.025,均 P<0.05);从主成分分析中,可以看出宫颈癌组的基因表达与健康组和癌前病变组明显不同,而且各组基因没有相关性,宫颈癌组、癌前病变组和健康组不同的基因表达有差异(F=5.361,P<0.05).结论 肿瘤相关的巨噬细胞在HR-HPV诱导的宫颈癌肿瘤微环境中发挥了重要的作用,干扰机体免疫水平,促进疾病的发生、发展.%Objective To discuss the role of tumor-associated macrophages(TAMs)in microenvironment of cervical carcinoma induced by high-risk human papillomavirus(HR-HPV).Methods A total of 100 patients with cervical carcinoma in Taizhou Hospital of Zhejiang Province during December 2014 to June 2017 were selected as cervical carcinoma group.And 30 patients with cervical pre-cancerous lesion hospitalized at the same period were selected as cervical pre-cancerous lesion group,while 30 individuals accepting physical examination at the same period were selected as health group.The expressions of viral proteins E2, E6,E5 and E7 of specimens from the above three groups were detected.The expressions of CD14,CD163,CD206 and CD68 as well as TAMs in the tumor tissue and para-cancerous tissue were detected.The differential gene expressions in different specimens were detected and the functional analysis was performed in transcriptomics by R software package.The expressions of M1/M2 factor screened in clinical specimens were detected further by the qRT-PCR method.Results There were significant differences in the positive rates of viral proteins E2,E6,E5,E7 and TAMs among three groups(χ2value was 6.392,5.091,7.392,4.883 and 5.691,respectively,all P<0.05),and the cervical carcinoma group was with the highest positive rate,followed by the cervical pre-cancerous lesion group,and in the health group,the positive rate was the lowest.The positive rates of CD14,CD163,CD206 and CD68 in the cervical carcinoma tissue of people in the cervical carcinoma group were higher than those in the cervical para-cancerous tissue(χ2value was 6.836,4.981,5.382 and 6.025,respectively,all P< 0.05).According to principal component analysis,the gene expression in the cervical carcinoma group was significantly different from that in the health group and the cervical pre-cancerous lesion group,and there was no correlation in the genes among three groups.Furthermore,the gene expressions among three groups were different(F= 5.361,P< 0.05).Conclusion The TAMs play an important role in tumor microenvironment of cervical carcinoma induced by HR-HPV,which can interfere with the immunity level of the body and promote the occurrence and development of the disease.