GC–MS-based untargeted plasma metabolomics identifies a 2-biomarker panel for possible diagnosis of precancerous cervical intraepithelial neoplasia stages from cervical cancer

Abstract

Abstract Cervical cancer (CC) remains a major health concern globally, much of the brunt of which is experienced by the low- and middle-income countries where screening in terms of cytology and DNA genotyping for the high-risk oncogenic subtypes of the human papilloma virus (hr-HPV) is either inadequate or performed rather late. In this study, we aimed to determine biomarkers or panels of biomarkers that are capable of diagnosing the precancerous cervical intraepithelial neoplasia (CIN) stages from healthy and CC patients via untargeted gas chromatography–mass spectrometry-based metabolomics. Various cross-comparisons were conducted from which differential metabolites were identified. The underlying metabolic pathways based on the differential metabolites identified from the various cross-comparisons mainly related to amino acids biosynthesis and metabolism and steroid hormone biosynthesis. From all cross-comparisons, two common metabolites namely, 2-methyl-1-propylamine (also known as isobutylamine) and estrone were found to possess excellent to good diagnostic abilities, especially in distinguishing the early stages of CIN (CIN I, CIN II) from healthy women and CC patients. These findings have clinical significance in the sense that, once validated the 2-biomarker panel could be adopted in clinical practice for early diagnosis of CIN and invasive carcinoma. This would therefore inform the choice of treatment to be initiated by the clinician.

Keywords

• Cervical cancer
• Cervical intraepithelial neoplasia
• Untargeted metabolomics
• Cytology
• High-risk human papilloma virus
• Diagnostic biomarkers