LABEL-FREE CERVICOVAGINAL FLUID PROTEOME PROFILING REFLECTS THE CERVIX NEOPLASTIC TRANSFORMATION.

Cervicovaginal fluid (CVF) is a valuable source of clinical information about the female reproductive tract in both non-pregnant and pregnant women. The aim of this study is to specify the CVF proteome at different stages of cervix neoplastic transformation by label-free quantitation approach based on LC-MS/MS method. The proteome composition of CVF from 40 women of reproductive age with HPV-associated cervix neoplastic transformation (LSIL, HSIL, CANCER) was investigated. Hierarchical clustering and principal component analysis (PCA) of the proteomic data obtained by a label-free quantitation approach shows the distribution of the sample set between four major clusters (NILM, LSIL, HSIL and CANCER) depending on the form of cervical lesion. Multisample ANOVA with subsequent Welch's t-test resulted in 117 that changed significantly across the four clinical stages, including 27 proteins significantly changed in cervical cancer. Some of them were indicated as promising biomarkers previously (ACTN4, VTN, ANXA1, CAP1, ANXA2, MUC5B). CVF proteomic data from the discovery stage was analyzed by the PLS-DA method to build a statistical model, allowing to differentiate severe dysplasia (HSIL, CANCER) from the mild/normal stage (NILM and LSIL) and ROC AUC were obtained on an independent set of 33 samples. The sensitivity of the model was 77% and the specificity - 94%, AUC was equal to 0.87. CVF proteome proved to be reflect the stage of cervical epithelium neoplastic process.

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