HPV E6 May Affect PACSIN2 Expression in Cervical Cancer Independently from Known Transcription Factors

Cervical cancer is the 4 th most common cancer in women.While the roles of E6 and E7 human papillomavirus (HPV) oncogenes in disrupting cell cycle control are known, the specific impact of HPV on immune gene regulation in cervical cancer is not fully understood.We hypothesized that if HPV genes regulate PACSIN2 expression via mechanisms independent of PACSIN2 transcription factors (TFs), a predictive model of PACSIN2 expression would have substantially better performance when using both TFs and HPV genes as input than either alone.Decision trees and XGBoost were used to understand the regulatory mechanisms of HPV genes and TFs on immune response genes.The XGBoost model, the best performer for TF-only input, yielded a Pearson correlation coefficient of 0.52; when both TF and HPV genes were included, a correlation of 0.69 in the XGBoost model was achieved, indicating a notably enhanced predictive accuracy due to the inclusion of HPV genes.The HPV gene E6 may exert a substantial regulatory influence on PACSIN2 expression, encouraging a path for further investigation.This influence was independent of the regulation by known PACSIN2 TFs.In addition, interactions between E6 and PACSIN2 TFs are likely mediated via E6 downregulating p53.