Identification of Pathways and Genes Associated with Chemoradiotherapy in Locally Advanced Cervical Cancer

Abstract: The standard treatment approach for locally advanced cervical cancer (LACC) is concurrent chemoradiotherapy (CCRT). However, resistance to radiotherapy and chemotherapy often leads to failure of LACC therapy. Thus, the key pathways and genes associated with CCRT in LACC should be identified urgently. The Weighted Gene Co-Expression Network Analysis (WGCNA) was used for the identification of highly correlated gene modules. A protein-protein interaction (PPI) network was constructed using STRING and hub genes were selected. Furthermore, single-cell transcriptome sequencing was used to elucidate the cell type composition of the cervix sample and analyze the expression levels of key genes in cells. We identified 580 differentially expressed genes (DEGs) in LACCk, which were mainly invovled in Human papillomavirus infection, focal adhesion, and ECM-receptor interaction signaling pathways. Ten hub genes (COL1A1, COL6A1, COL6A2, LAMA4, COL6A3, LAMC1, HSPG2, ITGA9, CTGF, PDGFRB) were screened for further study. We showed that COL1A1, COL6A1, COL6A2 were highly expressed after radiotherapy or chemoradiotherapy. By analyzing the single-cell sequence, we found that the main cell types in cervical tissue include Fibroblasts, Smooth muscle cells, Tissue stem cells, Endothelial cells, Progenitor cells, Epithelial cells, T cells, Basal cells, Macrophages, and Mast cells. COL1A1, COL6A1, COL6A2, COL6A3, CTGF, and PDGFRB were highly expressed in Progenitor cells. Human papillomavirus infection, focal adhesion, and ECM-receptor interaction signaling pathway are related to the failure of CCRT for LACC, which warrants further research to improve CCRT sensitivity in LACC targeting on these candidate genes or pathways.