Multi-omics analyses construct an inflammatory response based prognostic gene signature for cervical cancer and suggest tumor infiltrating monocytes subgroups as key players

Yidong ZhangJiawei ZhuKe HuJie Qiu^*Fuquan Zhang^*

• Peking Union Medical College Hospital (CAMS), Beijing, China

Inflammatory response in the tumour micro-environment contributes to the progression and treatment response of various types of cancers. However, for cervical cancer, a type of cancer initiated by the infection of HPV, the clinical relevance of inflammatory response and the underlying mechanisms remain to be elucidated. In this study, the RNA-seq and clinical data of cervical cancer patients was used to construct and validate a prognostic signature consisting of 16 inflammatory response related genes. Patients in the high-risk group defined by the inflammation gene signature had significantly worse survival. Bioinformatic analyses showed that the high and low risk groups had different immune landscapes, enriched biological pathways and predicted sensitivity to chemo-, radio- and immune-therapy. Integrated analysis of single cell and bulk RNA-seq data indicated that two subgroups of tumor infiltrating monocytes with opposite functions might be actively involved in the inflammatory response. Besides, SERPINE1 and ITGA5 expressed on endothelial cells might have synergic effects and regulate the infiltration of monocytes and macrophages. These findings were validated with our own RNA-seq data and additional public datasets. Overall, results in the study indicate that the inflammatory response in the tumour micro-environment of cervical cancer, possibly jointly regulated by multiple TIM subgroups, is associated with the prognosis and treatment response of cervical cancer patients and may be potential treatment targets.