宫颈小细胞癌HPV18整合模式介导超级增强子致癌机制研究

宫颈小细胞癌（Small Cell Carcinoma of the Cervix，SCCC）是一种极为罕见却颇具侵袭力的浸润性癌，局部晚期SCCC五年生存率低至0-14%。迄今，SCCC临床诊疗方案相当局限，其致癌机理研究也罕有文献涉及。我们前期研究首次提出92%SCCC存在HPV18感染（191/208）而几乎与HPV18/16以外型别无关，HPV18整合可能与c-MYC等重要基因拷贝数变异有关。然而，HPV18如何参与SCCC高度恶性特征形成有待深入研究。鉴于此，本项目以高危型HPV18整合为切入点阐明SCCC HPV18整合模式介导超级增强子启动Hub基因关键靶点诱导宿主癌基因/抑癌基因失衡以及相应免疫逃逸机制，以期为明确HPV18整合模式及其引起宿主基因组不稳定性提供实验依据，为SCCC高度恶性特征形成提供理论支撑，旨在为SCCC临床干预提供新思路，有利于防治关口前移。

Small cell carcinoma of the cervix (SCCC) is a rare but exceptionally aggressive cervical cancer. The 5-year survival rates for advanced stages of SCCC stand at a mere 0-14%. To date, early clinical diagnosis and effective therapeutic schemes for SCCC are almost nonexistent, and basic research related to its carcinogenesis mechanism remains rare. Our previous study first proposed that 92% of SCCCs have HPV18 infection (191/208) and are almost irrelevant to other types HPV except HPV18/16 and HPV18 integration was possibly associated with the copy number variation of c-MYC family. However, how HPV18 participates in the formation of highly malignant features of SCCC remains to be further studied. The high-risk type HPV18 integration patterns mediated super-enhancer activing key cancer gene target sites to induce the imbalance between oncogenes and tumor suppressor genes and immune escape in SCCC should be clarified. This project is expected to clarify the HPV18 integration pattern and provide experimental basis for host genome instability and provide theoretical support for the formation of highly malignant features of SCCC, untimately aiming at initiating new ideas for clinical intervention of SCCC, which is conducive for the prevention and control of SCCC in the early stage.