Metabonomic signature analysis of cervical carcinoma and precancerous lesions in women by 1H NMR spectroscopy

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.

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

“…Among the identified metabolites, the decrease in α-and β-glucose and the increase in lactate indicated a typical Warburg effect during cervical carcinogenesis [11,12]. Consistent with previous reports on blood-based metabolomics, we found an increase in LDL and alterations in multiple amino acids in cervical cancer tissues that might reflect an active lipid metabolism and a dual role of amino acid metabolism during tumor development [29]. Notably, tumor growth might drive the use of free amino acids in the blood circulation to facilitate rapid protein synthesis and altered energy metabolism in cervical cancer tissues [30].…”

“…According to HRMAS 1 H NMR, high positivity for HPVs, particularly HPV16, was observed in SCC and CIN II-III groups, whereas HPV negativity was observed in NC group (Table 2), which agrees with our previous reports [29,30]. These results suggest that the HPV detection data are likely not suitable for the analysis of the correlation between HPV16 infection and gene expression.…”

Alterations of Choline Phospholipid Metabolism in Endometrial Cancer Are Caused by Choline Kinase Alpha Overexpression and a Hyperactivated Deacylation Pathway

“…Abnormal NMR-detectable metabolic profiles have been reported in a number of tumor types, including breast, cervical, and colorectal cancers (9,(31)(32)(33)(34). However, this has not been studied in endometrial cancer.…”

NMR‐based metabolomics of biofluids in cancer

“…In a cohort of 31 controls and 31 patients with Barrett's esophagus (BE), Davis et al showed that urinary metabolomic profiles could discriminate the two groups with an AUC of 0.96 . Hasim et al showed that cervical intraepithelial neoplasia (CIN) could be discriminated from healthy women with a sensitivity and specificity of more than 90% based on NMR analysis of plasma samples . Wang et al showed in a Canadian cohort that urine NMR could detect colonic polyps with a sensitivity of 83% and a specificity of 51%, which was confirmed by Deng et al for a Chinese cohort.…”