Identifying small non-coding RNAs as biomarkers for cervical cancer.

Abstract

e17507 Background: Small non-coding RNAs (sncRNAs) that control post-transcriptional gene expression are attractive candidate molecular targets for cancer screening tests. We evaluated whether sncRNAs expression are markedly different in benign, precancerous, and cancerous cervical tissue. Methods: We examined the expression of six sncRNA species: circular RNAs (circRNAs) microRNAs (miRNAs), piwi-interacting RNA (piRNAs), small nuclear RNA (snRNAs), small nucleolar RNA (snoRNAs), and transfer RNA (tRNA), from archival formalin-fixed paraffin-embedded cervical specimen obtained from 172 women (74 benign, 58 high-grade squamous intraepithelial lesion (HSIL) and 40 invasive cervical cancer). We used DESeq2 to identify differentially expressed sncRNA molecules with adjusted p-value < 0.05 and at least 2-fold up- or down-regulation. Results: Comparing benign to HSIL samples, we foundseveral statistically significant, differentially expressed sncRNAs: 906 circRNAs (*circ_0066810, p=3.76x10-16), 87 miRNAs (*miR-149-5p, p=1.30x10-14), 11 piRNAs (*piR_016945, p=8.32x10-13), 32 snRNAs (*RNU1-17P, p=1.90x10-10), 5 snoRNAs (*SCARNA18, p=1.35x10-5), and 24 tRNA (*tRNA-Glu-TTC-8-1, p=6.45x10-17). Comparing benign to invasive cervical cancer samples, we also foundseveral statistically significant, differentially expressed sncRNAs: 3,192 circRNAs (*circ_0123115, p=7.46x10-50), 325 miRNAs (*miR-7-5p, p=6.72x10-36), 82 piRNAs (*piR-hsa-27513, p=1.44x10-15), 71 snRNAs (*RNU1-20P, p=1.37x10-45), 52 snoRNAs (*SNORD95, p=1.68x10-23), and 68 tRNA (*tRNA-Cys-GCA-9-3, p=1.01x10-21). * Indicates the sncRNA with the smallest p-value, for each specie. Conclusions: Our results identify sncRNAs with potential utility of as diagnostic and prognostic biomarkers, and therapeutic targets for cervical precancer and cancer.