PDF(Pubmed)
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.
摘要：
宫颈癌（CC）仍然是全球主要的健康问题，其中首当其冲的是低收入和中等收入国家,这些国家在细胞学和DNA基因分型方面对人乳头瘤病毒(hr-HPV)高危致癌亚型的筛查要么不充分,要么执行得相当晚.在这项研究中,我们旨在通过基于非靶向气相色谱-质谱的代谢组学,确定能够诊断健康患者和CC患者的宫颈癌前病变(CIN)阶段的生物标志物或一组生物标志物.进行各种交叉比较,从中鉴定差异代谢物。从各种交叉比较中确定的基于差异代谢物的基本代谢途径主要与氨基酸的生物合成和代谢以及类固醇激素的生物合成有关。从所有交叉比较来看，两种常见的代谢物，即，2-甲基-1-丙胺（也称为异丁胺）和雌酮被发现具有优异的诊断能力，特别是在区分CIN的早期阶段(CINI，CINII)来自健康女性和CC患者。这些发现具有临床意义,一旦验证，2-生物标志物组可以在临床实践中用于CIN和浸润性癌的早期诊断。因此,这将告知由临床医生开始的治疗的选择。
