Öz
Amaç: Bu çalışmanın amacı, hepatoselüler karsinomda dolaşımdaki mikroRNA-122'nin (miR-122) biyobelirteç olarak potansiyelini araştırmaktır.
Gereç ve Yöntem: Bu çalışmada, dolaşımdaki miR-122 seviyeleri, hepatoselüler karsinomun farklı klinik evreleri olan hastalarda gerçek zamanlı polimeraz zincir reaksiyonu ile ölçülmüştür. Ayrıca, bu veriler ile serum miR-122 seviyeleri arasındaki korelasyonu gözlemlemek için diğer laboratuvar ve klinik veriler de değerlendirilmiştir.
Bulgular: Hepatoselüler karsinom hastalarında serum miR-122 seviyeleri kontrol grubuna göre anlamlı olarak yüksek bulundu. (medyan miR-122 (min. - maks.); hastalar: 0,0104 (0-0,262); kontroller: 0,00187 (0-0,100), p <0,001). Serum miR-122 seviyesi 0.0038 cut-off değerinde eğri altında kalan alana göre hepatosellüler karsinom teşhisinde %67.4 sensitivite ve %74.4 spesifivite ortaya çıkardı. Bu cut off değerinde 1 yıllık, 3 yıllık ve 5 yıllık genel sağkalım oranları, bu değerin üstünde veya altında olan hastalar arasında istatistiksel olarak anlamlı bulunmadı.
Sonuç: Sonuçlarımız, dolaşımdaki miR-122'nin tek başına hepatoselüler karsinomun teşhisi, prognozu ve sürveyansı için uygun bir biyobelirteç olmayabileceğini göstermektedir. Bu nedenle, serum miR-122 ile birlikte diğer tanısal, klinik ve prognostik göstergelerin kullanılması ve bu konuda büyük ölçekli çalışmaların yapılması daha anlamlı olabilir.
Anahtar Kelimeler
Destekleyen Kurum
Cukurova Üniversitesi
Kaynakça
- Referans 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
- Referans 2. Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn). 2018;22:141-50.
- Referans 3. Petrick JL, McGlynn KA. The changing epidemiology of primary liver cancer. Curr Epidemiol Rep. 2019;6:104-11.
- Referans 4. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589-604.
- Referans 5. Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection. 2020;48:7-17.
- Referans 6. Zinkin NT, Grall F, Bhaskar K et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res. 2008;14:470-7.
- Referans 7. Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120:21-4.
- Referans 8. Zhang HH, Wang XJ, Li GX, Yang E, Yang NM. Detection of let-7a microRNA by real-time PCR in gastric carcinoma. World J Gastroenterol. 2007;13:2883-8.
- Referans 9. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther. 2009;9:703-11.
- Referans 10. Chen X, Ba Y, Ma L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997-1006.
- Referans 11. Hu Z, Chen X, Zhao Y et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28:1721-6.
- Referans 12. Ladeiro Y, Couchy G, Balabaud C et al. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatol. 2008;47:1955-63.
- Referans 13. Varnholt H, Drebber U, Schulze F et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatol. 2008;47:1223-32.
- Referans 14. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526-36.
- Referans 15. Kutay H, Bai S, Datta J et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 2006;99:671-8.
- Referans 16. Murakami Y, Yasuda T, Saigo K et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537-45.
- Referans 17. Xu J, Wu C, Che X et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50:136-42.
- Referans 18. Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011;6:e28486.
- Referans 19. Bignotti E, Calza S, Tassi RA et al. Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues. J Cell Mol Med. 2016;20:2341-8.
- Referans 20. Masè M, Grasso M, Avogaro L et al. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation. Sci Rep. 2017;7:41127.
- Referans 21. Wang K, Zhang S, Marzolf B et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A. 2009;106:4402-7.
- Referans 22. Köberle V, Kronenberger B, Pleli T et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442-9.
- Referans 23. Kojima K, Takata A, Vadnais C et al. MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma. Nat Commun. 2011;2:338.
- Referans 24. Tsai WC, Hsu PW, Lai TC et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatol. 2009;49:1571-82.
- Referans 25. Yang X, Sun L, Wang L, Yao B, Mo H, Yang W. LncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4. Biomed Pharmacother. 2019;118:109386.
- Referans 26. Amr KS, Elmawgoud Atia HA, Elazeem Elbnhawy RA, Ezzat WM. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Dis. 2017;4:215-21.
- Referans 27. Cakmak HA, Demir M. MicroRNA and cardiovascular diseases. Balkan Med J. 2020;37:60-71.
Öz
Purpose: The main purpose of our study is to research the potential of circulating microRNA-122 (miR-122)as a marker for hepatocellular carcinoma.
Materials and Methods: Circulating miR-122 levels were measured by real-time polymerase chain reaction in patients with varied stages of hepatocellular carcinoma. In addition, various other laboratory and clinical data of the participants were evaluated in order to observe the correlation between these data and serum miR-122 levels.
Results: Serum miR-122 levels were found significantly higher in hepatocellular carcinoma patients compared to the control group. (median miR-122 (min. – max.); patients: 0.0104 (0-0.262); controls: 0.00187 (0-0.100), p <0.001). For the cut-off value of serum miR-122 levels (0.0038), the area under the receiver operating characteristic curve analysis revealed 67.4% sensitivity and 74.4% specificity in hepatocellular carcinoma diagnosis. At this cut-off value, 1-year, 3-year and 5-year overall survival rates were not statistically different between patients with above or below this value.
Conclusion: Our results show that only serum miR-122 is not a suitable biomarker for the hepatocellular carcinoma. Thus, using other diagnostic indicators together with serum miR-122 may be clinically meaningful for which large-scale studies are warranted.
Anahtar Kelimeler
Hepatocellular carcinoma microRNA-122 circulating microRNA-122
Kaynakça
- Referans 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
- Referans 2. Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn). 2018;22:141-50.
- Referans 3. Petrick JL, McGlynn KA. The changing epidemiology of primary liver cancer. Curr Epidemiol Rep. 2019;6:104-11.
- Referans 4. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589-604.
- Referans 5. Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection. 2020;48:7-17.
- Referans 6. Zinkin NT, Grall F, Bhaskar K et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res. 2008;14:470-7.
- Referans 7. Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120:21-4.
- Referans 8. Zhang HH, Wang XJ, Li GX, Yang E, Yang NM. Detection of let-7a microRNA by real-time PCR in gastric carcinoma. World J Gastroenterol. 2007;13:2883-8.
- Referans 9. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther. 2009;9:703-11.
- Referans 10. Chen X, Ba Y, Ma L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997-1006.
- Referans 11. Hu Z, Chen X, Zhao Y et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28:1721-6.
- Referans 12. Ladeiro Y, Couchy G, Balabaud C et al. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatol. 2008;47:1955-63.
- Referans 13. Varnholt H, Drebber U, Schulze F et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatol. 2008;47:1223-32.
- Referans 14. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;28:3526-36.
- Referans 15. Kutay H, Bai S, Datta J et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 2006;99:671-8.
- Referans 16. Murakami Y, Yasuda T, Saigo K et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene. 2006;25:2537-45.
- Referans 17. Xu J, Wu C, Che X et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50:136-42.
- Referans 18. Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011;6:e28486.
- Referans 19. Bignotti E, Calza S, Tassi RA et al. Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues. J Cell Mol Med. 2016;20:2341-8.
- Referans 20. Masè M, Grasso M, Avogaro L et al. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation. Sci Rep. 2017;7:41127.
- Referans 21. Wang K, Zhang S, Marzolf B et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A. 2009;106:4402-7.
- Referans 22. Köberle V, Kronenberger B, Pleli T et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442-9.
- Referans 23. Kojima K, Takata A, Vadnais C et al. MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma. Nat Commun. 2011;2:338.
- Referans 24. Tsai WC, Hsu PW, Lai TC et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatol. 2009;49:1571-82.
- Referans 25. Yang X, Sun L, Wang L, Yao B, Mo H, Yang W. LncRNA SNHG7 accelerates the proliferation, migration and invasion of hepatocellular carcinoma cells via regulating miR-122-5p and RPL4. Biomed Pharmacother. 2019;118:109386.
- Referans 26. Amr KS, Elmawgoud Atia HA, Elazeem Elbnhawy RA, Ezzat WM. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Dis. 2017;4:215-21.
- Referans 27. Cakmak HA, Demir M. MicroRNA and cardiovascular diseases. Balkan Med J. 2020;37:60-71.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Eylül 2021 |
| Kabul Tarihi | 15 Temmuz 2021 |
| Yayımlandığı Sayı | Yıl 2021 Cilt: 46 Sayı: 3 |
