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Hepatosellüler karsinomda miR-4746'nın klinik önemi, kestirim değeri ve ifadesi için veri tabanı madenciliği

Year 2023, , 217 - 224, 30.06.2023
https://doi.org/10.31832/smj.1187165

Abstract

Amaç: MikroRNA'lar, hepatosellüler karsinomun (HCC) gelişiminde ve ilerlemesinde anahtar düzenleyicilerdir. Yakın tarihli bir çalışmada, miR-4746'nın HCC’de aşırı ifade edildiği bulunmuş olsa da miR-4746’nın HCC’deki farklı seviyelerde ifade edilmesi ve klinikopatolojik önemi belirsizliğini korumaktadır. Bu çalışmada miR-4746’nın gen ifade özelliğini, klinikopatolojik rolünü ve kestirim değerini hesaplamalı yaklaşımlar kullanarak değerlendirmeyi amaçladık.

Gereç ve Yöntemler: Çeşitli insan kanserlerinde miR-4746’nın gen ifade özelliği dbDEMC veri tabanı kullanılarak belirlendi. Ayrıca, HCC’de miR-4746 gen ifade seviyesini analiz etmek için ENCORI/Starbase v2 ve UALCAN veri tabanlarını kullandık. Ayrıca UALCAN veri tabanını kullanarak miR-4746’nın klinikopatolojik işlevini araştırdık. Son olarak, miR-4746’nın HCC’deki kestirim özelliğini belirleyebilmek için Kaplan-Meier plotter ve ENCORI/Starbase v2 veri tabanları aracılığıyla sağ kalım analizi ile gerçekleştirdik.

Bulgular: miR-4746, çeşitli insan kanserlerinde farklı gen ifade değerlerine sahipti ve normal örneklere kıyasla HCC dokularında önemli ölçüde arttığı gözlemlenmiştir. Klinikopatolojik analiz, miR-4746’nın kanser evresi, tümör derecesi, lenf bezi metastaz durumu, TP53 mutasyon durumu ve hastanın yaşı dahil olmak üzere farklı klinik parametrelerde farklı gen ifade seviyelerine sahip olduğunu koydu. Ek olarak, miR-4746’nın yüksek ifadesi, HCC’de kötü prognoz ile önemli ölçüde ilişkili olduğu bulunmuştur.

Sonuç: Bulgularımız, miR-4746’nın kötü kestirim ve çok kötü klinikopatolojik çıktılarla ilişkilendirilen onkojenik bir miRNA olabileceğini gösterdi. Ayrıca miR-4746, HCC’nin tümorogenezinde önemli bir role sahip olabilir ve potansiyel kestirim biyobelirteç olarak hizmet edebilir.

References

  • 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71: 209–249.
  • 2. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis, Gastroenterology. 2007; 132: 2557–2576.
  • 3. Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduction and Targeted Therapy. 2016 ; 1: 1–9.
  • 4. Cannell IG, Kong YW, Bushell M. How do microRNAs regulate gene expression? Biochem Soc Trans. 2008; 36: 1224–1231.
  • 5. Ardekani AM, Naeini MM. The role of microRNAs in human diseases. Avicenna J Med Biotechnol. 2010; 2(4): 161-179.
  • 6. Altan Z, Sahin Y. MiR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression. Molecular and Cellular Probes. 2022; 66: 101866.
  • 7. Liu X, Xiao C, Yue K, Chen M, Zhou H, Yan X. Identification of multi-omics biomarkers and construction of the novel prognostic model for hepatocellular carcinoma. Scientific Reports. 2022; 12: 1–12.
  • 8. Ren Y, Li Y, Zhang W, Yang K, Li J, Hu Y, et al. Mir-4746 inhibits the proliferation of colorectal cancer cells in vitro and in vivo by targeting CCND1, Biochem Biophys Res Commun. 2022; 594: 153–160.
  • 9. Xu F, Wang Y, Ling Y, Zhou C, Wang H, Teschendorff AE, et al. dbDEMC 3.0: Functional exploration of differentially expressed miRNAs in cancers of human and model organisms. Genomics Proteomics Bioinformatics. 2022; 22.
  • 10. Chandrashekar DK, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022; 25: 18–27.
  • 11. Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. J Med Internet Res. 2021; 23.
  • 12. Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, et al. MiRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells. 2020; 9.
  • 13. He B, Zhao Z, Cai Q, Zhang Y, Zhang P, Shi S. Mirna-based biomarkers, therapies, and resistance in cancer, Int J Biol Sci. 2020; 16: 2628–2647.

Mining database for the clinical significance, prognostic value and expression of miR-4746 in hepatocellular carcinoma

Year 2023, , 217 - 224, 30.06.2023
https://doi.org/10.31832/smj.1187165

Abstract

Abstract
Objective: MicroRNAs (miRNAs) are key regulators in the progression and development of hepatocellular carcinoma (HCC). In recent study the miR-4746 was found to be overexpressed in HCC, however, differential expression pattern and clinicopathological significance of miR-4746 in HCC remains unclear. In current study we aimed to evaluate expression profile, clinicopathological role and prognostic value of miR-4746 by using computational approaches.

Material and Methods: The expression profile of miR-4746 in various human cancers was determined using the dbDEMC database. Also, we used ENCORI/Starbase v2 and UALCAN databases to analyze miR-4746 expression level in HCC. Moreover, we investigated clinicopathological function of miR-4746 by using UALCAN database. Finally, survival analysis was performed to determine prognostic significance of miR-4746 in HCC by Kaplan-Meier plotter and ENCORI/Starbase v2 databases.

Results: The miR-4746 had differential expression patterns in various human cancers and was significantly upregulated in HCC tissues compared with normal samples. Clinicopathological analysis revealed that, miR-4746 was differentially expressed in different clinical parameters including cancer stage, tumor grade, nodal metastasis status, TP53 mutation status, and patient’s age. In addition, high expression of miR-4746 was significantly correlated with poor prognosis in HCC.

Conclusion: Our findings indicated that miR-4746 might be as an oncogenic miRNA which were correlated with poor prognosis and worse clinicopathological outcomes. Furthermore, miR-4746 might have an important role in tumorigenesis of HCC and it might serve as potential prognostic biomarker.

References

  • 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71: 209–249.
  • 2. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis, Gastroenterology. 2007; 132: 2557–2576.
  • 3. Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduction and Targeted Therapy. 2016 ; 1: 1–9.
  • 4. Cannell IG, Kong YW, Bushell M. How do microRNAs regulate gene expression? Biochem Soc Trans. 2008; 36: 1224–1231.
  • 5. Ardekani AM, Naeini MM. The role of microRNAs in human diseases. Avicenna J Med Biotechnol. 2010; 2(4): 161-179.
  • 6. Altan Z, Sahin Y. MiR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression. Molecular and Cellular Probes. 2022; 66: 101866.
  • 7. Liu X, Xiao C, Yue K, Chen M, Zhou H, Yan X. Identification of multi-omics biomarkers and construction of the novel prognostic model for hepatocellular carcinoma. Scientific Reports. 2022; 12: 1–12.
  • 8. Ren Y, Li Y, Zhang W, Yang K, Li J, Hu Y, et al. Mir-4746 inhibits the proliferation of colorectal cancer cells in vitro and in vivo by targeting CCND1, Biochem Biophys Res Commun. 2022; 594: 153–160.
  • 9. Xu F, Wang Y, Ling Y, Zhou C, Wang H, Teschendorff AE, et al. dbDEMC 3.0: Functional exploration of differentially expressed miRNAs in cancers of human and model organisms. Genomics Proteomics Bioinformatics. 2022; 22.
  • 10. Chandrashekar DK, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022; 25: 18–27.
  • 11. Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. J Med Internet Res. 2021; 23.
  • 12. Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, et al. MiRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells. 2020; 9.
  • 13. He B, Zhao Z, Cai Q, Zhang Y, Zhang P, Shi S. Mirna-based biomarkers, therapies, and resistance in cancer, Int J Biol Sci. 2020; 16: 2628–2647.
There are 13 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Zekiye Altan 0000-0002-1842-5619

Yunus Sahin 0000-0002-2721-6683

Aydın Karabulut 0000-0003-3969-8613

Ahmet Arslan 0000-0002-4015-7999

Early Pub Date June 27, 2023
Publication Date June 30, 2023
Submission Date October 11, 2022
Published in Issue Year 2023

Cite

AMA Altan Z, Sahin Y, Karabulut A, Arslan A. Hepatosellüler karsinomda miR-4746’nın klinik önemi, kestirim değeri ve ifadesi için veri tabanı madenciliği. Sakarya Tıp Dergisi. June 2023;13(2):217-224. doi:10.31832/smj.1187165

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