Proteomic and Metabolomic Analyses of HPV-Positive High-Grade Squamous Intraepithelial Lesions

Background/Objectives: Long-term exposure to high-risk human papilloma virus (HPV) leads to high-grade squamous intraepithelial lesions (HSILs), which may develop into cancer. Various proteins and metabolites change during the development of cervical cancer; thus, assessing the dysregulated molecules and pathways in HSILs is important to elucidate early pathological mechanisms and identify potential intervention targets. Methods: In this study, we performed proteomic and metabolomic analyses in five pairs of HPV-positive HSIL tissues and paired normal tissues. Immunohistochemistry (IHC) was applied to validate the levels of carnitine palmitoyltransferase 1A (CPT1A) in HSIL tissues. Quantitative real-time PCR and Western blot were used to detect the expression levels of CPT1A in cervical cancer cell lines. Results: In proteomic analysis, 836 proteins showed significant changes. Functional analyses of the differentially expressed proteins indicated that metabolic pathways, oxidative phosphorylation and ribosome are the top three enriched pathways. In metabolomic analysis, 105 metabolites were differentially altered. Most metabolites were involved in lipid metabolism, such as phosphatidylethanolamine (PE), phosphatidylinositol (PI) and L-palmitoylcarnitine. Integrated proteomics and metabolomics revealed that the metabolic pathway was the most enriched pathway that contained the maximum number of differentially expressed metabolites and proteins. In vitro, we found CPT1A was upregulated in HSIL tissues and in cervical cancer cell lines. Conclusions: Our findings characterize the protein and metabolite alterations in HSILs, which may represent molecular features associated with disease progression.