Proteogenomic Characterization of Human Uterine Cervical Cancer

We report a proteogenomic analysis of human cervical cancer. Mutation-phosphorylation correlations revealed associations of proliferation and invasion-related signaling pathways with somatic mutations in significantly mutated genes. mRNA-protein abundance correlations identified molecules with tumor promoting or suppressing functions correlating with patient survival. Integrated clustering of mRNA, protein, and phosphorylation data provided six subtypes (Sub1-6) of cervical cancer. Compared with the previous subtypes identified from transcriptome data, protein data further identified subgroups of squamous carcinoma and adenocarcinoma based on stromal and immune characteristics. In the squamous subgroups, Sub4 showed higher T-cell immunity than Sub5, and myeloid-derived suppressive immune cells that inhibit T-cell proliferation were enriched in Sub5. In the adeno subtypes, Sub3 had higher myofibroblasts that modulate anti-tumor immunity than Sub6. These stromal and immune features were consistent with the survival patterns of patients in the subtypes. Our proteogenomic analysis provides patient stratification and therapeutic targets in cervical cancer and improves our understanding of cancer biology.]]> Patients diagnosed with UCC, based on the final results of the pathology report, were included in the study. There is no selection bias in the recruitment.]]>