Figure S1: Differential expression of six miRNAs in urine, serum, cervical scrape, and tissue biopsies derived from healthy controls, pre-cancer and cervical cancer patients. The miRNA expression level of miR-21-5p, miR-155-5p, miR-199a-5p, miR-145-5p, miR218 -5p, and miR-34a-5p in (a) urine, (b) serum, (c) cervical scrape, and (d) tissue biopsies. Urine and serum samples were taken from pre-cancer and cervical cancer patients and compared to samples from healthy controls. In case of cervical scrape, the samples were derived from pre-cancer patients compared to samples from healthy volunteers, while in case of tissue biopsies, the samples were derived from cancer patient compared to samples from adjacent non-malignant tissues. **p≤ 0.01, ***p ≤ 0.001.
Figure S2: Correlation of expression pattern of miRNAs in cervical tissue biopsies and paired urine using Pearson’s correlation coefficient. Pearson’s correlation scatter plots for the correlation between the fold-change expression levels of (a) miR-21-5p, (b) miR-155-5p, (c) miR-199a-5p, (d) miR-145-5p, (e) miR-34a-5p, and (f) miR-218-5p in tissue biopsies and paired urine of cervical cancer patients.
Figure S3: Expression levels of miR-21-5p, miR-155-5p, miR-199a-5p, miR-145-5p, miR-218-5p, and miR-34a-5p in HPV16-positive and HPV16-negative urine, serum, and cervical scrape samples of cervical pre-cancer (a-c) and urine, serum, and tissue biopsies of cervical cancer patients (d-f).
Figure S4: (a-f) Differential expression of six miRNAs in pre-cancer, cancer and normal urine, and the ROC analyses of six miRNA detection. Box plot of miRNA expression in urine (upper: miR‐21-5p, miR‐155-5p and miR‐199a-5p; lower: miR‐145-5p, miR‐218-5p and miR‐34a-5p is normalized to U6. The lines inside the boxes indicate the medians. The boxes mark the interval between the 25th and 75th percentiles. The whiskers indicate the interval between and outside the 10th and 90th percentiles. A statistically significant difference is determined by Kruskal–Wallis test with Dunn's multiple comparison post‐hoc test, normal urine.
Figure S5: The target gene prediction and function analyses. The Venn diagrams represent the overlapping target genes of (a) miR-21-5p, (b) miR-155-5p, (c) miR-199a-5p, (d) miR-34a-5p, (e) miR-145-5p, and (f) miR-218-5p predicted by miRDB, Target Scan and DIANA microT‐CDS online analysis tools.
Figure S6A: Top 10 Gene ontology enrichment in (a) Biological, (b) Molecular, and (c) Cellular processes.
Figure S6B: Top 10 pathway enrichment analysis, including (a) KEGG and (b) REACTOME pathways.
Table S1: The expression of miRNAs in HPV positive and HPV negative cervical cancer cell line
Table S2: The expression of miRNAs according to HPV infection status in urine, serum, cervical scrape, and tissue biopsies derived from cervical pre-cancer and cancer patients
Table S3: The correlation of the expression of urine, serum and cervical scrape miRNAs with the clinicopathological parameters of cervical pre-cancer patients
Table S4: The correlation of the expression of urine and serum miRNAs with the clinicopathological parameters of cervical cancer patients
Table S5: Primers for amplification of human papilloma virus gene sequence
Table S6: MiRNA primer sequences used for Real-time PCR