分子标记可以预测由人乳头瘤病毒引起的宫颈病变向宫颈癌的进展和预后。
Molecular markers predicting the progression and prognosis of human papillomavirus-induced cervical lesions to cervical cancer.
发表日期:2023 Mar 31
作者:
Fatema Alzahraa Samy Amin, Zeba Un Naher, P Shaik Syed Ali
来源:
Cell Death & Disease
摘要:
持续人乳头瘤病毒(HPV)感染与99%的宫颈癌(CC)病例有关。 HPV 16和18型单独导致75%的CC病例,因此被认为是高风险型(HR-HPV)。 CC是全球妇女中第三常见的癌症。每年约有7000名患者死于宫颈癌。值得注意的是,并非每个HPV癌前病变患者都会发展成CC。本综述的目的是探讨分子和病毒生物标志物作为早期检测和预测HPV诱发的宫颈病变进展成CC的工具的利用。使用关键词CC筛查、HPV和最新分子生物标志物搜索数据库PubMed、Google Scholar、EBSCO。搜索时间框架在最近的7年内。排除了除CC以外的HPV诱导癌症研究,共检索到200篇符合条件的文章。在本综述中,我们探讨了CC中的HPV病毒学、毒力基因以及早期诊断/预后分子生物标志物的当前文献。 HPV致癌物性归因于各种早期蛋白(E5、E6、E7)的病毒表达。病毒致癌蛋白与细胞遗传学机制的相互作用改变了疾病不同阶段的许多基因的表达。 HR-HPV引起的宫颈病变与氧化性DNA损伤标记物和其他蛋白的过度表达相关。 标记物p16INK4a、程序性细胞死亡-1(PD-1)/程序性细胞死亡配体1、错配修复酶(MMR)、miRNA-377、肌动蛋白家族(CLDN)失调,与高风险病变相关。此外,高级别老年宫颈病变与高甲基化水平和高进展风险相关。将上述不同标志物添加到CC筛查方案中可能提供优先患者管理的分流。©2023年。 作者(s)在Springer-Verlag GmbH Germany的独家许可下,属于Springer Nature的一部分。
Persistent Human Papillomavirus (HPV) infection is linked to 99% of cervical cancer (CC) cases. HPV types 16 and 18 alone result in 75% of CC cases and thus are considered to be high-risk types (HR-HPV). CC is the third most common cancer among women globally. Approximately, 7000 patients die from it yearly. It is worthy to note that not every patient with HPV precancerous lesions will progress to CC.The objectives of this review is to explore the utilization of molecular and viral biomarkers as a tool for early detection and prediction of HPV-induced cervical lesions that might progress to CC.The data bases PubMed, Google Scholar, EBSCO were searched using keywords CC screening, HPV, and recent molecular biomarkers. The search time frame was within the last 7 years. Studies on HPV-induced cancers other than CC were excluded; a total of 200 eligible articles were retrieved.In this review we explored the current literature about HPV virology, virulence genes and early diagnostic/prognostic molecular biomarkers in CC. The oncogenic property of HPV is attributed to viral expression of various early proteins (E5, E6, E7). The interaction between viral oncoproteins and the cellular genetic apparatus alters the expression of many genes at different phases of the disease. There was an association between cervical lesions induced by HR-HPV and the overexpression of markers of oxidative DNA damage and other proteins. The markers p16INK4a, programmed cell death-1 (PD-1)/programmed cell death ligand 1, mismatch repair enzymes (MMR), miRNA-377, claudin family (CLDN) are dysregulated and are associated with high risk lesions. Furthermore, advanced older cervical lesions were associated with high methylation levels and higher risk to progress to CC.Adding different the above markers to the CC screening program scheme might offer a triage for prioritizing patient management.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.