Plasma-Based Metabolomics Profiling of High-Risk Human Papillomavirus and their Emerging Roles in the Progression of Cervical Cancer

Abstract

High-risk human papillomavirus (HR-HPV) is the main etiological factor for cervical cancer. Accumulating evidence has suggested the active role of metabolites in the initiation and progression of cancers. This study explored the plasma metabolic profiles of HPV-16 positive (HPV16 (+)), HPV-18 positive (HPV18 (+)), and HPV negative (CTL) individuals using a nontargeted metabolomics approach. C8 ceramide-1-Phosphate (d18 : 1/8 : 0) was found to inhibit cervical cancer cell proliferation and migration in vitro, evidenced by CCK8 experiments, a cell migration test, RT-qPCR, and western blotting. The underlying mechanism demonstrated that C8 inhibited proliferation and migration in cervical cancer cells via the MAPK/JNK1 signaling pathway. These findings may contribute to the clinical treatment of HR-HPV-induced cervical cancer by intervening in its initiation and progression.

Salivary metabolomic identification of biomarker candidates for oral melanoma and oral squamous cell carcinoma in dogs

“… 64 Decreased concentrations of aspartyl‐hydroxyproline have been observed in the plasma of patients with human papillomavirus during the progression of cervical cancers. 65 Our study reinforces the connection between hydroxyprolyl‐hydroxyproline and L‐alpha‐aspartyl‐L‐hydroxyproline and proline metabolism in oral tumors in dogs. Future research should explore potentially related proteins and pathways, such as gelatinolytic and prolidase activity, as referenced in studies of breast cancer.…”

“…These alterations in collagen metabolism, coupled with increased enzymatic activities, may signify tissue remodeling characteristic of the invasive phenotype, potentially promoting metastatic dissemination in breast cancer 64 . Decreased concentrations of aspartyl‐hydroxyproline have been observed in the plasma of patients with human papillomavirus during the progression of cervical cancers 65 . Our study reinforces the connection between hydroxyprolyl‐hydroxyproline and L‐alpha‐aspartyl‐L‐hydroxyproline and proline metabolism in oral tumors in dogs.…”

“…64 Decreased concentrations of aspartyl-hydroxyproline have been observed in the plasma of patients with human papillomavirus during the progression of cervical cancers. 65 Our study reinforces the connection between hydroxyprolyl-hydroxyproline and L-alpha-aspartyl-L-hydroxyproline and proline metabolism in oral tumors in dogs.…”

“…In addition, we found decreased concentrations of isomer 2 of gly‐norvaline and isomer 2 of norvaline in OSCC. Norvaline functions as a structural analog of valeric acid and an inhibitor of arginase 1, an enzyme that converts arginine into ornithine and urea 65 . The combination of L‐norvaline and doxorubicin has demonstrated significant inhibition of the proliferation of breast cancer cells 66 .…”

Research progress of metabolomics in cervical cancer

“…The LDL receptors on the surface of malignant tumor cells are very sensitive to cholesterol, as well as with a substantial increase in the demand for cholesterol by malignant tumor tissues, which results in elevating the levels of LDL that carry cholesterol [ 33 ]. This study [ 34 ] is the first to identify C8-ceramide-1-phosphate as an important lipid metabolite that modulates cervical cancer cell function. In addition, they also identified that other lipids, such as LysoPC and PC, may also involve cervical cancer progression, requiring further investigation.…”