Biomarcadores para diagnóstico diferencial de patologías en próstata
Resumen
El diagnóstico diferencial de las enfermedades prostáticas, que incluyen la prostatitis, hiperplasia prostática benigna (HPB) y el cáncer de próstata (CaP), se basa usualmente en la determinación del antígeno prostático específico (PSA) y en los resultados del examen rectal digital (ERD). Sin embargo, estas pruebas tienen limitaciones importantes en términos de sensibilidad y especificidad, lo que puede derivar en falsos negativos, falsos positivos, sobrediagnósticos y en la realización de biopsias innecesarias, incrementando así el riesgo de procedimientos invasivos y el impacto psicológico en los pacientes. Debido a estas limitaciones, ha surgido un creciente interés en la identificación y validación de nuevos biomarcadores diagnósticos que puedan diferenciar de manera más precisa entre afecciones benignas y malignas en la glándula prostática. En esta revisión, se llevó a cabo una búsqueda sistemática en las bases de datos científicos: PUBMED, THE LENS y SCOPUS, siguiendo las recomendaciones establecidas por PRISMA. Se incluyeron artículos en inglés publicados en un periodo comprendido entre los años 2014 y 2024, que proporcionen información relevante sobre biomarcadores que identifiquen y diferencien las enfermedades prostáticas. De un total de 726 estudios identificados, se seleccionaron 19 artículos, que cumplieron con todos los criterios de elegibilidad. Los resultados de la revisión sugieren que las investigaciones dirigidas a diferenciar la prostatitis de las otras patologías prostáticas siguen siendo limitadas. No obstante, se ha encontrado que la determinación de cierto tipo de metabolitos séricos de ácidos orgánicos podrían ser una herramienta prometedora para establecer una mejor precisión en el diagnóstico diferencial entre las enfermedades prostáticas.
Descargas
Citas
Abramovic, I., Pezelj, I., Dumbovic, L., Abramovic, L. S., Vodopic, T., Bulimbasic, S., Stimac, G., Bulic-Jakus, F., Kulis, T., Bojanac, A. K., Tomas, D., Ulamec, M., & Sincic, N. (s. f.). LGALS3 cfDNA methylation in seminal fluid as a novel prostate cancer biomarker outperforming PSA. https://doi.org/10.1002/pros.24749
Alahdal, M., Perera, R. A., Moschovas, M. C., Patel, V., & Perera, R. J. (2023). Current advances of liquid biopsies in prostate cancer: Molecular biomarkers. Molecular Therapy Oncolytics, 30, 27-38. https://doi.org/10.1016/j.omto.2023.07.004
Bansal, N., Kumar, D., Gupta, A., Chandra, D., Sankhwar, S. N., & Mandhani, A. (2017). Relevance of MIC-1 in the Era of PSA as a Serum Based Predictor of Prostate Cancer: A Critical Evaluation. Scientific Reports, 7(1), 16824. https://doi.org/10.1038/s41598-017-17207-2
Boehm, B. E., York, M. E., Petrovics, G., Kohaar, I., & Chesnut, G. T. (2023). Biomarkers of Aggressive Prostate Cancer at Diagnosis. International Journal of Molecular Sciences, 24(3), 2185. https://doi.org/10.3390/ijms24032185
Bosch, J. L., Hop, W. C., Kirkels, W. J., & Schröder, F. H. (1995). Natural history of benign prostatic hyperplasia: Appropriate case definition and estimation of its prevalence in the community. Urology, 46(3 Suppl A), 34-40. https://doi.org/10.1016/s0090-4295(99)80248-9
Brant, W. E., & Helms, C. A. (2007). Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins.
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263. https://doi.org/10.3322/caac.21834
Cannarella, R., Condorelli, R. A., Barbagallo, F., La Vignera, S., & Calogero, A. E. (2021). Endocrinology of the Aging Prostate: Current Concepts. Frontiers in Endocrinology, 12, 554078. https://doi.org/10.3389/fendo.2021.554078
Ciszkowicz, E., Porzycki, P., Semik, M., Kaznowska, E., & Tyrka, M. (2020). MiR-93/miR-375: Diagnostic Potential, Aggressiveness Correlation and Common Target Genes in Prostate Cancer. International Journal of Molecular Sciences, 21(16), 5667. https://doi.org/10.3390/ijms21165667
Coradduzza, D., Solinas, T., Azara, E., Culeddu, N., Cruciani, S., Zinellu, A., Medici, S., Maioli, M., Madonia, M., & Carru, C. (2022). Plasma Polyamine Biomarker Panels: Agmatine in Support of Prostate Cancer Diagnosis. Biomolecules, 12(4), 514. https://doi.org/10.3390/biom12040514
Coradduzza, D., Solinas, T., Balzano, F., Culeddu, N., Rossi, N., Cruciani, S., Azara, E., Maioli, M., Zinellu, A., Miglio, M. R. D., Madonia, M., Falchi, M., & Carru, C. (2022). miRNAs as Molecular Biomarkers for Prostate Cancer. The Journal of Molecular Diagnostics, 24(11), 1171-1180. https://doi.org/10.1016/j.jmoldx.2022.05.005
Derin, O., Fonseca, L., Sanchez-Salas, R., & Roberts, M. J. (2020). Infectious complications of prostate biopsy: Winning battles but not war. World Journal of Urology, 38(11), 2743-2753. https://doi.org/10.1007/s00345-020-03112-3
Dülgeroğlu, Y., & Eroğlu, O. (2019). Diagnostic performance of microRNAs in the circulation in differential diagnosis of BPH, chronic prostatitis and prostate cancer. Turkish Journal of Biochemistry, 44(4), 417-425. https://doi.org/10.1515/tjb-2018-0198
Ferro, M., Buonerba, C., Terracciano, D., Lucarelli, G., Cosimato, V., Bottero, D., Deliu, V. M., Ditonno, P., Perdonà, S., Autorino, R., Coman, I., De Placido, S., Di Lorenzo, G., & De Cobelli, O. (2016). Biomarkers in localized prostate cancer. Future Oncology, 12(3), 399-411. https://doi.org/10.2217/fon.15.318
Fredsøe, J., Rasmussen, A. K. I., Thomsen, A. R., Mouritzen, P., Høyer, S., Borre, M., Ørntoft, T. F., & Sørensen, K. D. (2018). Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine. European Urology Focus, 4(6), 825-833. https://doi.org/10.1016/j.euf.2017.02.018
Friedemann, M., Horn, F., Gutewort, K., Tautz, L., Jandeck, C., Bechmann, N., Sukocheva, O., Wirth, M. P., Fuessel, S., & Menschikowski, M. (2021). Increased Sensitivity of Detection of RASSF1A and GSTP1 DNA Fragments in Serum of Prostate Cancer Patients: Optimisation of Diagnostics Using OBBPA-ddPCR. Cancers, 13(17), Article 17. https://doi.org/10.3390/cancers13174459
Fu, S., Zhang, X., Niu, Y., & Wang, R.-T. (2018). Prostate Specific Antigen, Mean Platelet Volume, and Platelet Distribution Width in Combination to Discriminate Prostate Cancer from Benign Prostate Hyperplasia. Asian Pacific Journal of Cancer Prevention : APJCP, 19(3), 699-702. https://doi.org/10.22034/APJCP.2018.19.3.699
Ge, Y., Xu, B., Cai, H., Jing, W., Ouyang, Q., Yuan, Q., Li, X., Fan, Y., Shen, Y., Shi, Q., Wang, Q., Cui, L., Yin, X., & Ma, G. (2023). Diagnostic role of plasma ORM2 in differentiating prostate cancer from benign prostatic hyperplasia. Journal of Cancer Research and Clinical Oncology, 149(6), 2301-2310. https://doi.org/10.1007/s00432-022-04380-9
Gooren, L. (2003). Androgen deficiency in the aging male: Benefits and risks of androgen supplementation. The Journal of Steroid Biochemistry and Molecular Biology, 85(2-5), 349-355. https://doi.org/10.1016/s0960-0760(03)00206-1
He, J., Han, Z., Luo, W., Shen, J., Xie, F., Liao, L., Zou, G., Luo, X., Guo, Z., Li, Y., Li, J., & Chen, H. (2023). Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.998447
He, J., Luo, W., Shen, J., Han, Z., Xie, F., Guo, Z., Luo, X., & Li, Y. (2022, mayo 13). Patent application: CN114487216A Biomarker and diagnostic kit for distinguishing prostatitis and prostatic cancer. https://worldwide.espacenet.com/patent/search/family/081475776/publication/CN114487216A?q=pn%3DCN114487216A
He, S., Shi, J., Mao, J., Luo, X., Liu, W., Liu, R., & Yang, F. (2019). The expression of miR-375 in prostate cancer: A study based on GEO, TCGA data and bioinformatics analysis. Pathology, Research and Practice, 215(6), 152375. https://doi.org/10.1016/j.prp.2019.03.004
Jedinak, A., Curatolo, A., Zurakowski, D., Dillon, S., Bhasin, M. K., Libermann, T. A., Roy, R., Sachdev, M., Loughlin, K. R., & Moses, M. A. (2015). Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer. BMC Cancer, 15, 259. https://doi.org/10.1186/s12885-015-1284-z
Kachakova, D., Mitkova, A., Popov, E., Popov, I., Vlahova, A., Dikov, T., Christova, S., Mitev, V., Slavov, C., & Kaneva, R. (2015). Combinations of Serum Prostate-Specific Antigen and Plasma Expression Levels of let-7c, miR-30c, miR-141, and miR-375 as Potential Better Diagnostic Biomarkers for Prostate Cancer. DNA and Cell Biology, 34(3), 189-200. https://doi.org/10.1089/dna.2014.2663
Khan, F. U., Ihsan, A. U., Khan, H. U., Jana, R., Wazir, J., Khongorzul, P., Waqar, M., & Zhou, X. (2017). Comprehensive overview of prostatitis. Biomedicine & Pharmacotherapy, 94, 1064-1076. https://doi.org/10.1016/j.biopha.2017.08.016
Kohaar, I., Petrovics, G., & Srivastava, S. (2019). A Rich Array of Prostate Cancer Molecular Biomarkers: Opportunities and Challenges. International Journal of Molecular Sciences, 20(8), 1813. https://doi.org/10.3390/ijms20081813
Krilaviciute, A., Becker, N., Lakes, J., Radtke, J. P., Kuczyk, M., Peters, I., Harke, N. N., Debus, J., Koerber, S. A., Herkommer, K., Gschwend, J. E., Meissner, V. H., Benner, A., Seibold, P., Kristiansen, G., Hadaschik, B., Arsov, C., Schimmöller, L., Giesel, F. L., … Albers, P. (2023). Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer. European Urology Oncology, 6(6), 566-573. https://doi.org/10.1016/j.euo.2023.09.008
Litwin, M. S., & Tan, H.-J. (2017). The Diagnosis and Treatment of Prostate Cancer: A Review. JAMA, 317(24), 2532-2542. https://doi.org/10.1001/jama.2017.7248
Luo, W., He, J., Shen, J., Han, Z., Xie, F., Guo, Z., Zou, G., & Li, Y. (2022, mayo 13). Patent application: CN114487214A Biomarker for distinguishing benign prostatic hyperplasia and prostatitis and application thereof.
Markin, P. A., Brito, A., Moskaleva, N., Fodor, M., Lartsova, E. V., Shpot, Y. V., Lerner, Y. V., Mikhajlov, V. Y., Potoldykova, N. V., Enikeev, D. V., Lyundup, A. V., & Appolonova, S. A. (2020). Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia. Laboratory Medicine, 51(6), 566-573. https://doi.org/10.1093/labmed/lmaa008
Mian, B. M., Naya, Y., Okihara, K., Vakar-Lopez, F., Troncoso, P., & Babaian, R. J. (2002). Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy. Urology, 60(5), 836-840. https://doi.org/10.1016/S0090-4295(02)01950-7
Naji, L., Randhawa, H., Sohani, Z., Dennis, B., Lautenbach, D., Kavanagh, O., Bawor, M., Banfield, L., & Profetto, J. (2018). Digital Rectal Examination for Prostate Cancer Screening in Primary Care: A Systematic Review and Meta-Analysis. The Annals of Family Medicine, 16(2), 149-154. https://doi.org/10.1370/afm.2205
Nguyen, A., Ehsan Sheikh, A. A., Ryu, M., Butt, M. A., Mirza, S. A., Shekhar, R., & Sheikh, A. B. (s. f.). Digital Rectal Exam in the Acute Hospital Setting: Bridging Patient Experience and the Physician Perspective. Journal of Community Hospital Internal Medicine Perspectives, 12(6), 64-68. https://doi.org/10.55729/2000-9666.1119
Pang, C., Liu, M., Fang, W., Guo, J., Zhang, Z., Wu, P., Zhang, Y., & Wang, J. (2016). MiR-139-5p is Increased in the Peripheral Blood of Patients with Prostate Cancer. Cellular Physiology and Biochemistry, 39(3), 1111-1117. https://doi.org/10.1159/000447819
Park, W. Y., Song, G., Park, J. Y., Ahn, K. S., Kwak, H. J., Park, J., Lee, J. H., & Um, J.-Y. (2022). Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3. Cell Death & Disease, 13(6), 554. https://doi.org/10.1038/s41419-022-04995-3
Porcacchia, A. S., Pires, G. N., Ortiz, V., Andersen, M. L., & Tufik, S. (2022). Prostate cancer mortality and costs of prostate surgical procedures in the Brazilian public health system. International Brazilian Journal of Urology : Official Journal of the Brazilian Society of Urology, 48(3), 583-590. https://doi.org/10.1590/S1677-5538.IBJU.2021.0781
Porzycki, P., Ciszkowicz, E., Semik, M., & Tyrka, M. (2018). Combination of three miRNA (miR-141, miR-21, and miR-375) as potential diagnostic tool for prostate cancer recognition. International Urology and Nephrology, 50(9), 1619-1626. https://doi.org/10.1007/s11255-018-1938-2
Prensner, J. R., Rubin, M. A., Wei, J. T., & Chinnaiyan, A. M. (2012). Beyond PSA: The Next Generation of Prostate Cancer Biomarkers. Science Translational Medicine, 4(127). https://doi.org/10.1126/scitranslmed.3003180
Rashid, M. M., Alam, A. K. M. K., Habib, A. K. M. K., Rahman, H., Hossain, A. K. M. S., Salam, M. A., & Rahman, S. (2012). Efficacy of lower cut off value of serum prostate specific antigen in diagnosis of prostate cancer. Bangladesh Medical Research Council Bulletin, 38(3), 90-93. https://doi.org/10.3329/bmrcb.v38i3.14333
Salido-Guadarrama, A. I., Morales-Montor, J. G., Rangel-Escareño, C., Langley, E., Peralta-Zaragoza, O., Colin, J. L. C., & Rodriguez-Dorantes, M. (2016). Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone. Molecular Medicine Reports, 13(6), 4549. https://doi.org/10.3892/mmr.2016.5095
Smith, D. S., Humphrey, P. A., & Catalona, W. J. (1997). The early detection of prostate carcinoma with prostate specific antigen: The Washington University experience. Cancer, 80(9), 1852-1856.
Sreekumar, A., Poisson, L. M., Rajendiran, T. M., Khan, A. P., Cao, Q., Yu, J., Laxman, B., Mehra, R., Lonigro, R. J., Li, Y., Nyati, M. K., Ahsan, A., Kalyana-Sundaram, S., Han, B., Cao, X., Byun, J., Omenn, G. S., Ghosh, D., Pennathur, S., … Chinnaiyan, A. M. (2009). Metabolomic Profiles Delineate Potential Role for Sarcosine in Prostate Cancer Progression. Nature, 457(7231), 910-914. https://doi.org/10.1038/nature07762
Stella, M., Russo, G. I., Leonardi, R., Carcò, D., Gattuso, G., Falzone, L., Ferrara, C., Caponnetto, A., Battaglia, R., Libra, M., Barbagallo, D., Di Pietro, C., Pernagallo, S., Barbagallo, C., & Ragusa, M. (2024). Extracellular RNAs from Whole Urine to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia. International Journal of Molecular Sciences, 25(18), Article 18. https://doi.org/10.3390/ijms251810079
Tombal, B. (2012). Toward the End of Blind Prostate Biopsies? European Urology, 62(6), 997-998. https://doi.org/10.1016/j.eururo.2012.07.048
Wang, Y., Lieberman, R., Pan, J., Zhang, Q., Du, M., Zhang, P., Nevalainen, M., Kohli, M., Shenoy, N. K., Meng, H., You, M., & Wang, L. (2016). miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1. Molecular Cancer, 15(1), 70. https://doi.org/10.1186/s12943-016-0556-9
Wang, Y.-H., Ji, J., Wang, B.-C., Chen, H., Yang, Z.-H., Wang, K., Luo, C.-L., Zhang, W.-W., Wang, F.-B., & Zhang, X.-L. (2018). Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer. Cellular Physiology and Biochemistry, 46(2), 532-545. https://doi.org/10.1159/000488620
Yan, C., Kim, Y.-H., Kang, H. W., Seo, S. P., Jeong, P., Lee, I.-S., Kim, D., Kim, J. M., Choi, Y. H., Moon, S.-K., Yun, S. J., & Kim, W.-J. (2015). Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer. Journal of Korean Medical Science, 30(12), 1784-1792. https://doi.org/10.3346/jkms.2015.30.12.1784
Yang, B., Liu, Z., Ning, H., Zhang, K., Pan, D., Ding, K., Huang, W., Kang, X.-L., Wang, Y., & Chen, X. (2016). MicroRNA-21 in peripheral blood mononuclear cells as a novel biomarker in the diagnosis and prognosis of prostate cancer. Cancer Biomarkers: Section A of Disease Markers, 17(2), 223-230. https://doi.org/10.3233/CBM-160634
Zaichick, V., & Zaichick, S. (2014). Age-related histological and zinc content changes in adult nonhyperplastic prostate glands. Age, 36(1), 167-181. https://doi.org/10.1007/s11357-013-9561-8
Zhang, M., Chen, L., Yuan, Z., Yang, Z., Li, Y., Shan, L., Yin, B., Fei, X., Miao, J., & Song, Y. (2016). Combined Serum and EPS-urine Proteomic Analysis Using iTRAQ Technology for Discovery of Potential Prostate Cancer Biomarkers. Discovery Medicine, 22(122), 281-295.
Zhu, C., Wang, D.-Q., Zi, H., Huang, Q., Gu, J.-M., Li, L.-Y., Guo, X.-P., Li, F., Fang, C., Li, X.-D., & Zeng, X.-T. (2021). Epidemiological trends of urinary tract infections, urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019. Military Medical Research, 8, 64. https://doi.org/10.1186/s40779-021-00359-8
Zniber, M., Vahdatiyekta, P., & Huynh, T.-P. (2024). Discrimination of serum samples of prostate cancer and benign prostatic hyperplasia with 1H-NMR metabolomics. Analytical Methods, 16(41), 7043-7053. https://doi.org/10.1039/D4AY01109K
Derechos de autor 2025 Elizabeth Barreto
Esta obra está bajo licencia internacional Creative Commons Reconocimiento 4.0.
.png)
.png)
1.png)
