目的:探讨HOPX基因在宫颈癌组织和血清中的表达水平及其对宫颈癌HeLa细胞的作用及其机制，并分析其与肿瘤标志物CEA和CA125 表达的相关性。方法：选取2015 年6 月至2017 年12 月天津市滨海人民医院和武清区人民医院50 例宫颈癌患者癌组织、癌旁组织和外周血清样本，同时取50 例正常人的血清样本。qRT-PCR检测宫颈癌组织和血清中HOPX的表达水平，免疫组化染色检测宫颈癌患者血清中HOPX 蛋白的表达，通过NCBI-GEO和TCGA数据库收集宫颈癌癌组织标本和患者预后的相关数据，分析HOPX基因在宫颈癌组织中的表达水平及其与患者预后的相关性。过表达的HOPX和对照的质粒转染HeLa细胞后，MTT和克隆形成实验检测转染的HeLa细胞的增殖能力，Transwell 实验检测HeLa 细胞迁移和侵袭能力，Western blotting检测其EMT相关蛋白的表达。结果：标本检测和数据库分析均显示，HOPX mRNA和蛋白在宫颈癌肿瘤组织及血清中均低表达，且与患者生存期呈正相关(r=0.736，P<0.05)；HOPX 在组织及血清中表达与CEA 和CA125 的表达显著负相关（r=-0.678,P<0.05 ）。过表达HOPX抑制HeLa细胞增殖、迁移和侵袭能力，而且能够促进HeLa细胞中ETM相关的E-cadherin 的表达、抑制Vimentin和ICAM1 的表达（均P<0.05 或P<0.01）。结论：HOPX基因在宫颈癌组织及血清中相对低表达，且与CEA和CA125 水平呈负相关，与患者的生存期呈正相关。HOPX结合肿瘤标志物CEA/ CA125 联合检测可提高宫颈癌患者的早期诊断率，也为宫颈癌的精准治疗提供一个新的思路。

Objective: To investigate the expression of HOPX gene in cervical cancer tissues and blood serum as well as its effect on cervical cancer HeLa cells, and to analyze its correlation to tumor maker CEA and CA125. Methods: 50 pairs of cervical cancer tissues and para-cancerous tissues as well as the peripheral blood samples from patients with cervical cancer, who were treated at Tianjin Binhai People’s Hospital and Tianjin Wuqing People’s Hospital from June 2015 to December 2017, were collected for this study; in addition,50 samples of blood serum from healthy people were used as control. Real-time quantitative PCR (qRT-PCR) and immumohistochemical staining (IHC) were used to detect mRNA and protein expressions of HOPX in tissue and serum samples, NCBI-GEO data base and TCGA data base were used to collect the information on HOPX gene and patients’prognosis, and the correlation between HOPX expression and patients’prognosis was analyzed. Vectors over-expressing HOPX or control vectors were transfected into HeLa cells; MTT assay and colony formation assay were used to examine the proliferation ability of HeLa cells, Tranwell assay was used to detect the migration and invasion of HeLa cells, and Western blotting was used to detect the expression of EMT-related proteins. Results:Both sample examination and data base information showed that the expression level of HOPX was down-regulated in tissue and serum samples of cervical cancer patients and was positively related with the survival of patients (r=0.736，P<0.05); while it’s expression was negatively related to the level of CEA and CA125 in cervical cancer tissues and serum (r=-0.678, P<0.05). HOPX over-expression inhibited cell proliferation, migration and invasion, promoted the expression of E-cadherin but inhibited the expression of Vimentin and ICAM1 (all P<0.05 or P<0.001). Conclusion: HOPX is low expressed in cervical cancer tissues and blood samples, and negatively correlated with CEA and CA125, but positively correlated with the survival of patients. Thus, combination of HOPX and CEA/CA125 may improve the early diagnosis rate of cervical cancer and provide a new strategy for precision treatment of cervical cancer in future.

国家自然科学基金资助项目（No. 91629302, 81572790）