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. 2019 Apr 24;44:675–690. doi: 10.1016/j.ebiom.2019.04.028

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© 2019 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Fig. 1 — HPV infection, dysplasia, and invasive cervical carcinoma (ICC) divergently impacted the cervicovaginal metabolic profile. A) Principal component analysis (PCA) showed a distinct cervicovaginal metabolome profile in ICC patients compared to Ctrl HPV (−), Ctrl HPV (+), LSIL, and HSIL patient groups. The difference was significant on both PC1 and PC2 axes. HSIL group was significantly different than Ctrl HPV (−) group on PC2 axis. Boxplots represent median, first and third quartile, minimum and maximum values in the dataset. Shaded ellipses represent 95% confidence intervals of the cluster centroids. Mann-Whitney U test p values represented as *p  < .05, **p < .01, ***p < .001. B) Number of metabolites detected in each group. ICC patients had significantly greater number of metabolites in comparison to patients in the Ctrl HPV (+), LSIL, and HSIL groups. However, there was no significant difference between the ICC and Ctrl HPV (−) groups. ns = not significant. The trend analysis showed that the trend was polynomial (p = .01). C) Number of unique and shared metabolites among the groups visualized on a Venn diagram. Majority of the metabolites were detected in the all groups. ICC group had the greatest number of metabolites that were not detected in any of the participants in other groups. Supplementary Table 2 contains the list of metabolites that are different in each group. D) Enrichment and depletions of metabolites among patient groups visualized by Cytoscape metabolic network analysis. The node size is proportional to the magnitude of differences observed among the groups. Red and blue nodes represent enriched and depleted metabolites, respectively. In comparison to all other patient groups, ICC patients had an enrichment of metabolites that belong to lipid, amino acid, carbohydrate, and xenobiotic metabolism. Amino acids and their metabolites were depleted in Ctrl HPV (+), LSIL, and HSIL groups. Dipeptides were significantly depleted in the HSIL group compared to Ctrl HPV (−). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)