Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Sample Collection
2.2. Total RNA Extraction
2.3. miRNA Expression Profiling by Microarray Analysis
2.4. Validation of DEmiRs by Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)
2.5. Array Express Dataset for In Silico Analysis of miRNA Expression in PeC
2.6. Pathway Enrichment Analysis of the Predicted Targets of the DEmiRs and Establishment of miRNA-mRNA Interaction Networks
2.7. mRNA Expression Profiling by a High-Throughput Nanofluidic qRT-PCR Platform
2.8. GEO Dataset for In Silico Analysis of Deregulated Gene Expression in PeC
2.9. Gene Set Enrichment Analysis (GSEA) of Deregulated Genes in PeC
2.10. DNA Extraction and Human Papillomavirus (HPV) Detection
2.11. Statistical Analyses
3. Results
3.1. Patients, Treatment, and Follow Up
3.2. miRNAs Expression Profiles, Interaction Networks of miRNA and Predicted Target Genes and Pathway Enrichment Analysis
3.3. Deregulated mRNA Expression Profiling in PeC
3.4. Penile Carcinogenesis Alters Expression Profiles of miRNA-mRNA Pairs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients | Total Sample n (%) | Microarray Sample n (%) | Validation Sample n (%) |
---|---|---|---|
Number of patients | 24 | 11 | 13 |
Age at surgery-Mean (SD) years old | 61.8 (16.1) | 61.6 (14.2) | 61.9 (18.2) |
Follow up-Median (range) months | 39.8 (2–68) | 47.5 (8–62) | 34.9 (2–61) |
Smoking history | 14 (58.3) | 8 (72.7) | 6 (46.1) |
cT | |||
cT1 | 3 (12.5) | 2 (18.2) | 1 (7.7) |
cT2 | 13 (5.2) | 4 (36.4) | 9 (69.2) |
cT3 | 8 (33.3) | 5 (45.4) | 3 (23.1) |
cN | |||
cN0 | 9 (37.5) | 5 (45.4) | 4 (30.8) |
cN1 | 8 (33.3) | 3 (27.3) | 5 (38.4) |
cN2 | 4 (16.7) | 3 (27.3) | 1 (7.7) |
cN3 | 3 (12.5) | 0 (0) | 3 (23.1) |
Penectomy | |||
Partial | 17 (70.8) | 7 (63.6) | 10 (76.9) |
Total | 7 (29.2) | 4 (36.4) | 3 (23.1) |
Grade | |||
I | 3 (12.5) | 2 (18.2) | 1 (7.7) |
II | 13 (54.2) | 6 (54.5) | 7 (53.9) |
III | 8 (33.3) | 3 (27.3) | 5 (38.4) |
T Stage | |||
pT1 | 4 (16.6) | 3 (27.2) | 1 (7.7) |
pT2 | 13 (54.2) | 4 (36.4) | 9 (69.2) |
pT3 | 7 (29.2) | 4 (36.4) | 3 (23.1) |
Inguinal Lymphadenectomy | 16 (66.7) | 7 (63.6) | 9 (69.2) |
Pelvic Lymphadenectomy | 4 (16.7) | 2 (18.1) | 2 (15.4) |
Lymph node metastasis | 12 (50.0) | 6 (54.5) | 6 (46.2) |
Presence of HPV infection | 8 (33.3) | 3 (27.3) | 5 (38.4) |
Tumor Size-Mean (SD) cm | 4.75 (2.27) | 4.93 (2.50) | 4.59 (2.15) |
Lymphovascular invasion | 6 (25.0) | 3 (27.3) | 3 (23.1) |
Perineural invasion | 10 (41.7) | 4 (36.4) | 6 (46.2) |
Group Risk (EAU) | |||
Low | 1 (4.2) | 1 (9.1) | 0 (0) |
Intermediate | 3 (12.5) | 2 (18. 2) | 1 (7.7) |
High | 20 (83.3) | 8 (72.7) | 12 (92.3) |
Regulation | DEmiR | Microarray | qRT-PCR | |||
---|---|---|---|---|---|---|
FC | FDR | FC | SD | FDR | ||
Downregulated | miR-432-5p | 0.07 | 0.0048 * | 0.41 | 0.51 | 0.004 * |
miR-487b-3p | 0.12 | 0.0079 * | 0.44 | 0.45 | 0.004 * | |
miR-145-5p | 0.18 | 0.0088 * | 0.33 | 0.37 | 0.005 * | |
miR-30a-5p | 0.21 | 0.0067 * | 0.57 | 0.32 | 0.002 * | |
miR-149-5p | 0.29 | 0.0308 * | 0.79 | 1.04 | 0.097 | |
Upregulated | miR-200a-5p | 2.93 | 0.0048 * | 3.48 | 1.28 | 0.004 * |
miR-224-5p | 6.59 | 0.0083 * | 5.70 | 3.19 | 0.001 * | |
miR-31-3p | 12.38 | 0.0002 * | 41.62 | 41.43 | 0.004 * | |
miR-31-5p | 38.32 | 0.0048 * | 122.28 | 127.75 | 0.001 * |
Regulation in Our Study | miRNA | E-MTAB-3087 Dataset |
---|---|---|
log2 (Normalized Counts + 1) | ||
Downregulated | miR-30a-5p * | −8.165 |
miR-432-5p * | −7.947 | |
miR-487b-3p * | −6.236 | |
miR-145-5p * | −3.425 | |
Upregulated | miR-200a-5p | −0.551 |
miR-224-5p | −5.815 | |
miR-31-3p | −3.342 | |
miR-31-5p * | 2.914 |
Reg | DEG | FC | FDR | DEG | FC | FDR | DEG | FC | FDR |
---|---|---|---|---|---|---|---|---|---|
Down | ABCB1 | 0.24 | <0.001 * | LATS2 | 0.58 | 0.004 * | RIPK3 | 0.53 | <0.001 * |
ALDH1A1 | 0.09 | <0.001 * | MDM2 | 0.71 | 0.003 * | SAV1 | 0.45 | <0.001 * | |
BCL2 | 0.31 | <0.001 * | MLH1 | 0.77 | 0.007 * | STAT3 | 0.66 | <0.001 * | |
CCND1 | 0.61 | 0.007 * | NANOG | 0.33 | 0.005 * | STK4 | 0.65 | 0.002 * | |
EGR1 | 0.19 | <0.001 * | NRP1 | 0.48 | <0.001 * | TCF7L2 | 0.36 | <0.001 * | |
FGF2 | 0.18 | <0.001 * | PEBP1 | 0.53 | <0.001 * | TLR4 | 0.28 | <0.001 * | |
FOS | 0.18 | <0.001 * | PITX2 | 0.30 | <0.001 * | TP53 | 0.57 | 0.003 * | |
HOXA9 | 0.51 | 0.003 * | PPARGC1A | 0.11 | <0.001 * | TWIST1 | 0.18 | <0.001 * | |
KAT6A | 0.47 | <0.001 * | PTEN | 0.55 | <0.001 * | ZEB1 | 0.23 | <0.001 * | |
KLF4 | 0.22 | <0.001 * | RECK | 0.24 | <0.001 * | ||||
KMT2A | 0.40 | <0.001 * | RHOA | 0.66 | <0.001 * | ||||
Up | IL1A | 13.39 | <0.001 * | MMP1 | 28.00 | <0.001 * | SFN | 4.26 | 0.004 * |
MCM2 | 2.14 | <0.001 * | MMP12 | 9.97 | <0.001 * | VEGFA | 2.06 | <0.001 * |
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Furuya, T.K.; Murta, C.B.; Murillo Carrasco, A.G.; Uno, M.; Sichero, L.; Villa, L.L.; Cardilli, L.; Coelho, R.F.; Guglielmetti, G.B.; Cordeiro, M.D.; et al. Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis. Cancers 2021, 13, 4745. https://doi.org/10.3390/cancers13194745
Furuya TK, Murta CB, Murillo Carrasco AG, Uno M, Sichero L, Villa LL, Cardilli L, Coelho RF, Guglielmetti GB, Cordeiro MD, et al. Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis. Cancers. 2021; 13(19):4745. https://doi.org/10.3390/cancers13194745
Chicago/Turabian StyleFuruya, Tatiane Katsue, Claudio Bovolenta Murta, Alexis Germán Murillo Carrasco, Miyuki Uno, Laura Sichero, Luisa Lina Villa, Leonardo Cardilli, Rafael Ferreira Coelho, Giuliano Betoni Guglielmetti, Mauricio Dener Cordeiro, and et al. 2021. "Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis" Cancers 13, no. 19: 4745. https://doi.org/10.3390/cancers13194745