Abstract
(1)H nuclear magnetic resonance (NMR)-based metabonomics has been used to characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to model the systematic variation related to patients with CIN or CSCC with healthy controls. Potential metabolic biomarkers were identified using database comparisons, and the one-way analysis of variance (ANOVA) test was used to examine the significance of the metabolites. Compared with plasma obtained from the healthy controls, plasma from patients with CIN had higher levels of very-low density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and glycoprotein. Plasma from patients with CSCC had higher levels of acetate and formate, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine and tyrosine compared with the plasma of the healthy controls. In addition, compared with the plasma of patients with CIN, the plasma of CSCC patients had higher levels of acetate, formate, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine, acetylcysteine, myo-inositol, glycoprotein, α-glucose and β-glucose, together with lower levels of acetone, unsaturated lipid and carnitine. Moreover, the profiles showed high feasibility and specificity by statistical analysis with OPLS-DA compared to the Thinprep cytology test (TCT) by setting the histopathological outcome as standard. The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemic metabolic response to cancer, which may be used to identify potential early diagnostic biomarkers of the cancer and to establish clinical diagnostic methods.
Highlights
Cervical cancer (CC) is a high-risk human papillomavirus (h-HPV)‐induced tumor
The resonances in these spectra were assigned to individual metabolites and confirmed using the two dimensional nuclear magnetic resonance (NMR) methods 1H-1H homonuclear correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY) and J-Resolved spectroscopy (J-Res)
There were several cases showing an overlap between patients with Cervical intraepithelial neoplasia (CIN) and those with cervical squamous cell carcinomas (CSCC) (Fig. 2C), Principal component analysis (PCA) differentiated between the disease and control samples and showed the potential to distinguish between the precancerous and cancer cases with a high specificity
Summary
Cervical cancer (CC) is a high-risk human papillomavirus (h-HPV)‐induced tumor. Over 500,000 new cases of CC are diagnosed worldwide every year and 130,000 of these are in China, most of which are cervical squamous cell carcinomas (CSCC) [1,2]. Despite the advances in surgery and chemotherapy that have been made over the last 20 years, the overall survival rate for patients with CSCC has not changed significantly. The high mortality rate of CSCC occurs primarily due to the majority of women being diagnosed at an advanced stage of the disease when the 5-year survival rate is 8-12%. Patients who are accurately diagnosed with earlier stage or precancerous diseases have a 5-year survival rate of 90%. Mucins present difficult problems by forming sticky layers or sheets of disorganized cords which appear irregularly in the smear specimen. These approaches tend to contribute insufficient diagnostic sensitivity and specificity
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