Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico
Abstract
:1. Introduction
2. Results
2.1. Identification of DEmiRNAs in PDAC
2.2. Systematic Validation of DEmiRNAs in PDAC
2.3. Identification of miRNA Signatures in the Plasma of Patients with PDAC
2.4. Serum miRNA Signatures with Potential Value in the Diagnosis of PDAC
2.5. miR-221-3p and miR-222-3p as Biomarkers of Poor Survival in Patients with PDAC
2.6. Target Gene Prediction and Functional Analysis of Four DEmiRNAs in PDAC
2.7. Putative Target Genes of Four DEmiRNAs in PDAC Tumors Represent Prognostic Factors in Patients with PDAC
3. Discussion
4. Materials and Methods
4.1. The Tissue and Plasma Samples
4.2. Ethics Approval and Consent to Participate
4.3. Tissue Macrodissection and Total RNA Extraction
4.4. Plasma miRNA Isolation and cDNA Synthesis
4.5. miRNA Microarray Assays
4.6. miRNA Differential Expression Analysis
4.7. miRNA Expression by RT-qPCR
4.8. Bioinformatics Analysis of miRNAs and Gene Expression
4.9. miRNA Target Gene Identification
4.10. ROC Curve Analysis
4.11. ROC Curve Combinations
4.12. Survival Analysis
4.13. Statistical Analysis
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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Type of Sample | Characteristic | Controls n = 48 | Patients n = 86 |
---|---|---|---|
Age | |||
Tissue (n = 68) | Median (range) | 50 (26–78) | 63 (40–86) |
Plasma (n = 66) | Median (range) | 46 (27–62) | 63 (41–83) |
Gender | |||
Tissue (n= 68) | Male | 17 | 17 |
Female | 11 | 23 | |
Plasma (n = 66) | Male | 9 | 21 |
Female | 11 | 25 | |
Alcohol | |||
Tissue (n = 68) | Yes | 0 | 0 |
No | 0 | 0 | |
No data | 28 | 40 | |
Plasma (n = 66) | Yes | 0 | 9 |
No | 0 | 31 | |
No data | 20 | 6 | |
Smoking | |||
Tissue (n = 68) | Yes | 0 | 0 |
No | 0 | 0 | |
No data | 28 | 40 | |
Plasma (n = 66) | Yes | 0 | 16 |
No | 0 | 20 | |
No data | 20 | 10 | |
Ethnicity | |||
Tissue (n = 68) | Mexican-Mestizo | 28 | 40 |
Plasma (n = 66) | Mexican-Mestizo | 20 | 46 |
Tumor size | |||
Tissue (n = 68) | ≤4 cm | - | 9 |
>4 cm | - | 18 | |
No data | - | 13 | |
Plasma (n = 66) | ≤4 cm | - | 1 |
>4 cm | - | 0 | |
No data | - | 45 | |
TNM | |||
Tissue (n = 68) | I | - | 0 |
II | - | 18 | |
III | - | 8 | |
IV | - | 11 | |
No data | - | 3 | |
Plasma (n = 66) | I | - | 1 |
II | - | 5 | |
III | - | 18 | |
IV | - | 20 | |
No data | - | 2 | |
Differentiation grade | |||
Tissue (n = 68) | G1 | - | 2 |
G2 | - | 30 | |
G3 | - | 7 | |
No data | - | 1 | |
Plasma (n = 66) | G1 | - | 0 |
G2 | - | 0 | |
G3 | - | 0 | |
No data | - | 46 | |
Survival (Tissue/Plasma) | |||
Tissue (n = 68) | Short: ≤14 months | - | 15 |
Long: >14 months | - | 7 | |
No data | - | 18 | |
Plasma (n = 66) | Short: ≤14 months | - | 0 |
Long: >14 months | - | 0 | |
No data | - | 46 |
Transcript_ID | logFC | AveExpr | t | p-Value | FDR |
---|---|---|---|---|---|
Overexpressed miRNAs | |||||
miR-222-3p | 2.8844 | 10.8590 | 10.7525 | 9.96 × 10−9 | 6.41 × 10−7 |
miR-31-5p | 4.1967 | 9.7829 | 10.7844 | 9.56 × 10−9 | 6.53 × 10−7 |
miR-210-3p | 4.3097 | 8.0389 | 10.3553 | 1.69 × 10−8 | 7.75 × 10−7 |
miR-10b-5p | 3.2291 | 6.3356 | 10.5711 | 1.27 × 10−8 | 9.64 × 10−7 |
miR-203a | 3.5790 | 6.0323 | 9.9259 | 3.06 × 10−8 | 1.30 × 10−6 |
miR-10a-5p | 4.4917 | 8.5372 | 9.5532 | 5.19 × 10−8 | 2.38 × 10−6 |
miR-345-5p | 3.0996 | 5.9820 | 8.6866 | 1.88 × 10−7 | 2.88 × 10−6 |
miR-155-5p | 2.7886 | 9.5953 | 8.4357 | 2.78 × 10−7 | 3.96 × 10−6 |
miR-100-5p | 3.0294 | 10.4069 | 8.2603 | 3.66 × 10−7 | 4.38 × 10−6 |
miR-708-5p | 4.1888 | 6.7173 | 8.0084 | 5.49 × 10−7 | 6.25 × 10−6 |
miR-221-3p | 2.2323 | 10.7475 | 7.6056 | 1.06 × 10−6 | 1.10 × 10−5 |
miR-146a-5p * | 3.2269 | 8.8496 | 7.5014 | 1.27 × 10−6 | 1.26 × 10−5 |
miR-150-5p | 3.5555 | 8.7285 | 7.4770 | 1.32 × 10−6 | 1.27 × 10−5 |
miR-664b-3p | 3.1629 | 5.9450 | 8.1304 | 4.51 × 10−7 | 1.35 × 10−5 |
miR-92b-3p | 3.3605 | 5.8241 | 7.3678 | 1.59 × 10−6 | 1.45 × 10−5 |
miR-425-5p | 2.6038 | 8.3962 | 6.4191 | 8.51 × 10−6 | 7.36 × 10−5 |
Downregulated miRNA | |||||
miR-148a-3p | −4.5795 | 7.7280 | −9.7445 | 3.95 × 10−8 | 9.37 × 10−7 |
miRNA | Forward | Reverse |
---|---|---|
miR-222-3p | GCAGAGCTACATCTGGCT | CCAGTTTTTTTTTTTTTTTACCCAGT |
miR-31-5p | GCGCAGCTGTGCGTGTGACA | GTCCAGTTTTTTTTTTTTTTTAGCTATG |
miR-210-3p | GCGCAGCTGTGCGTGTGACA | GTTTTTTTTTTTTTTTCAGCCGCT |
miR-10b-5p | CAGTACCCTGTAGAACCGA | GGTCCAGTTTTTTTTTTTTTTTCAC |
miR-203a | CAGGTGAAATGTTTAGGACCA | GGTCCAGTTTTTTTTTTTTTTTCTAGT |
miR-10a-5p | GCAGTACCCTGTAGATCCGA | GGTCCAGTTTTTTTTTTTTTTTCAC |
miR-345-5p | GGCTGACTCCTAGTCCAG | GGTCCAGTTTTTTTTTTTTTTTGAG |
miR-155-5p | CGCAGTTAATGCTAATCGTGATAG | GGTCCAGTTTTTTTTTTTTTTTAACC |
miR-100-5p | CAGAACCCGTAGATCCGA | GTCCAGTTTTTTTTTTTTTTTACAAG |
miR-708-5p | CAGAAGGAGCTTACAATCTAGC | GTCCAGTTTTTTTTTTTTTTTCCCA |
miR-221-3p | GCAGAGCTACATTGTCTGCT | CAGTTTTTTTTTTTTTTTGAAACCCA |
miR-150-5p | AGTCTCCCAACCCTTGTACCA | GGTCCAGTTTTTTTTTTTTTTTCACT |
RT-primer | CAGGTCCAGTTTTTTTTTTTTTTTVN | |
RNU6 | CTCGCTTCGGCAGCACATATACT | ACGCTTCACGAATTTGCGTGTC |
miR-39-3p | GTCACCGGGTGTAAATCAG | GGTCCAGTTTTTTTTTTTTTTTTTCAAG |
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Álvarez-Hilario, L.G.; Salmerón-Bárcenas, E.G.; Ávila-López, P.A.; Hernández-Montes, G.; Aréchaga-Ocampo, E.; Herrera-Goepfert, R.; Albores-Saavedra, J.; Manzano-Robleda, M.d.C.; Saldívar-Cerón, H.I.; Martínez-Frías, S.P.; et al. Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico. Int. J. Mol. Sci. 2023, 24, 15193. https://doi.org/10.3390/ijms242015193
Álvarez-Hilario LG, Salmerón-Bárcenas EG, Ávila-López PA, Hernández-Montes G, Aréchaga-Ocampo E, Herrera-Goepfert R, Albores-Saavedra J, Manzano-Robleda MdC, Saldívar-Cerón HI, Martínez-Frías SP, et al. Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico. International Journal of Molecular Sciences. 2023; 24(20):15193. https://doi.org/10.3390/ijms242015193
Chicago/Turabian StyleÁlvarez-Hilario, Lissuly Guadalupe, Eric Genaro Salmerón-Bárcenas, Pedro Antonio Ávila-López, Georgina Hernández-Montes, Elena Aréchaga-Ocampo, Roberto Herrera-Goepfert, Jorge Albores-Saavedra, María del Carmen Manzano-Robleda, Héctor Iván Saldívar-Cerón, Sandra Paola Martínez-Frías, and et al. 2023. "Circulating miRNAs as Noninvasive Biomarkers for PDAC Diagnosis and Prognosis in Mexico" International Journal of Molecular Sciences 24, no. 20: 15193. https://doi.org/10.3390/ijms242015193