临床与实验病理学杂志2025，Vol.41Issue(4)：474-482,9.DOI:10.13315/j.cnki.cjcep.2025.04.010
基于细胞外囊泡DNA甲基化标志物探讨子宫颈癌侵袭转移的风险
Exploring the risk of tumor invasion and metastasis in cervical cancer based on ex-tracellular vesicle DNA methylation biomarkers
摘要
Abstract
Purpose To investigate the predictive value of the methylation regulator heterogeneous nuclear ribonu-cleoprotein C(HNRNPC)in the extracellular vesicles(EVs)derived from cervical cancer cells for tumor invasion and metastasis.Methods In vitro experiments were conducted using a human normal cervical epithelial cell line(Hcer-Epic),three cervical cancer cell lines(HeLa,SiHa and CaSki)and human umbilical vein endothelial cells(HU-VECs).HNRNPC protein expression was assessed by Western blot.CaSki cells were transfected with either sh-NC or sh-HNRNPC,and EVs were subsequently isolated from culture supernatant.The effects of EVs on the proliferation,migration and invasion of SiHa cells,as well as on angiogenesis in HUVECs,were investigated respectively.For tissue microarray analysis,normal cervical tissues(n=8),low-grade squamous intraepithelial lesions(LSIL,n=32)and high-grade squamous intraepithelial lesions(HSIL,n=37),and cervical carcinoma specimens(n=153)were ob-tained from our institution.Based on HNRNPC immunoscores,cervical cancer patients were divided into two groups:high(n=99)and low(n=54)HNRNPC expression group,and their clinicopathological features and prognosis were compared.Results Compared with HcerEpic cells,the expression of HNRNPC increased in SiHa,HeLa and CaSki cells.In SiHa cells treated with EVs from CaSki cell,the group receiving EVs from sh-HNRNPC-transfected CaSki cells showed significantly reduced proliferation,colony formation,migration,and invasion compared with the sh-NC-EVs group(P＜0.05).Similarly,in HUVECs treated with CaSki-EVs,compared with sh-NC-EVs group,the sh-HNRNPC-EVs group demonsteated significantly lower protein expression of PCNA and VEGFA and reduced angiogene-sis length(P＜0.05).HNRNPC expression gradually increased during the transformation of cervical epithelial cells(F=106.9,P＜0.001),and was significantlyelevated in HSIL and cervical cancer tissues compared with normal tis-sues(P＜0.001).Moreover,in cervical cancer,high HNRNPC expression was significantly related to poorer cellular differentiation,larger tumor size,parametrial and vaginal infiltration,advanced FIGO stage,and pelvic lymph node metastasis(P＜0.05).Kaplan-Meier analysis showed that that patients with high HNRNPC expression had significant-ly shorter overall survival post-surgery compared with those with low expression(P＜0.05).Conclusion EVs contai-ning HNRNPC contribute to cervical cancer progression by promoting tumor growth,invasion,and angiogenesis,there-by accelerating metastasis.In addition,high HNRNPC expression in cervical cancer tissue is related to poor prognosis of patients,indicating that EV-associated HNRNPC may serve as a potential therapeutic target.关键词
子宫颈肿瘤/细胞外囊泡/核内不均一核糖核蛋白C/侵袭转移Key words
cervical neoplasms/extracellular vesicle/heterogeneous nuclear ribonucleoprotein C/invasion and metas-tasis分类
临床医学引用本文复制引用
何薇薇,赵妍,李能,谢琦,吴菲..基于细胞外囊泡DNA甲基化标志物探讨子宫颈癌侵袭转移的风险[J].临床与实验病理学杂志,2025,41(4):474-482,9.基金项目
湖南省卫生健康委员会科研项目(202202115219) Scientific Research Project of Hunan Provincial Health and Wellness Committee(202202115219) （202202115219）
