Cervical cancer incidence and mortality are rapidly growing. GLOBOCAN estimates that this neoplasia incises on 3.3% and represents 3.2% of deaths in 2018 worldwide. In women, cervical cancer ranks second in incidence and mortality behind breast cancer. Human papillomavirus (HPV) is responsible for more than 90 percent of cervical cancer cases worldwide. Besides 70% of this incidence is associated with the persistent infection with high risk human papillomavirus (HR-HPV) 16 and 18, also involved in many types of oral and anogenital cancer. HPV infection is related to alterations of cell cycle, cell death, immune system, deregulation of energetic metabolism.
Warburg effect emphasizes the energetic metabolic change observed in many types of cancer, which could be due to mitochondrial dysfunctions or structural changes. Mitochondria sense cancer metabolism as disease goes to developing. Proteomic data offers some relevant mitochondrial proteins, however solid conclusions cannot make since some mitochondrial events are supposed or difficult to correlate.
Analyzing the mitochondrial proteome in a model of HR-HPV’s in cervical cancer (HaCat: control, C-33A: HPV-, SiHa: HPV-16 and CaLo: HPV-18) by means of Principal Component Analysis (PCA), followed of enrichment and PPI networks analyses; we identify a set of proteins related to different cancer HR-HPV mechanisms.
SiHa cells (HPV 16, the most frequently HPV in cervical cancer) follows a Warburg pattern with, glycolytic and viral response proteins. On the other way CaLo cells (HPV 18) interacts straightly to OXPHOS complexes, maybe inducing mitochondrial structural changes, ROS increase, HIF I stabilization, among other changes; following a different cancer mechanism.
This strategy helps to define biomarkers or molecular targets of cervical cancer in mitochondrial proteome, since it is able to detect differences between cervical cancer variants and focus in specific targets.
Part of this work was supported by CONACyT grant 220790 and DGAPA-PAPIIT grants IN207519 and IN-213216.