Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, Artaman A, Ayele TA, Barac A, Bensenor I, Berhane A, Bhutta Z, Castillo-Rivas J, Chitheer A, Choi JY, Cowie B, Dandona L, Dandona R, Dey S, Dicker D, Phuc H, Ekwueme DU, Zaki MS, Fischer F, Fürst T, Hancock J, Hay SI, Hotez P, Jee SH, Kasaeian A, Khader Y, Khang YH, Kumar A, Kutz M, Larson H, Lopez A, Lunevicius R, Malekzadeh R, McAlinden C, Meier T, Mendoza W, Mokdad A, Moradi-Lakeh M, Nagel G, Nguyen Q, Nguyen G, Ogbo F, Patton G, Pereira DM, Pourmalek F, Qorbani M, Radfar A, Roshandel G, Salomon JA, Sanabria J, Sartorius B, Satpathy M, Sawhney M, Sepanlou S, Shackelford K, Shore H, Sun J, Mengistu DT, Topór-Mądry R, Tran B, Ukwaja KN, Vlassov V, Vollset SE, Vos T, Wakayo T, Weiderpass E, Werdecker A, Yonemoto N, Younis M, Yu C, Zaidi Z, Zhu L, Murray CJL, Naghavi M, Fitzmaurice C (2017) The Burden of Primary Liver Cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol 3(12):1683–1691. https://doi.org/10.1001/jamaoncol.2017.3055
Article
PubMed Central
Google Scholar
Anwar WA, Khaled HM, Amra HA, El-Nezami H, Loffredo CA (2008) Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res 659(1–2):176–184. https://doi.org/10.1016/j.mrrev.2008.01.005
Article
CAS
PubMed
Google Scholar
Rosenbaum E, Begum S, Brait M, Zahurak M, Maldonado L, Mangold LA, Eisenberger MA, Epstein JI, Partin AW, Sidransky D, Hoque MO (2012) AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy. Prostate 72(10):1133–1139. https://doi.org/10.1002/pros.22461
Article
CAS
PubMed
Google Scholar
Shiraz OB, Galehdari H, Yavarian M, Geramizadeh B (2011) Possible down regulation of the p16 gene promoter in individuals with hepatocellular carcinoma. Hepat Mon 11(9):719–723. https://doi.org/10.5812/kowsar.1735143X.732
Article
PubMed
PubMed Central
Google Scholar
Lim WJ, Kim KH, Kim JY, Jeong S, Kim N (2019) Identification of DNA-methylated CpG islands associated with gene silencing in the adult body tissues of the ogye chicken using RNA-seq and reduced representation bisulfite sequencing. Front Genet 10:346. https://doi.org/10.3389/fgene.2019.00346
Article
CAS
PubMed
PubMed Central
Google Scholar
Subramaniam MM, Chan JY, Yeoh KG, Quek T, Ito K, Salto-Tellez M (2009) Molecular pathology of RUNX3 in human carcinogenesis. Biochim Biophys Acta 1796(2):315–331. https://doi.org/10.1016/j.bbcan.2009.07.004
Article
CAS
PubMed
Google Scholar
Nomoto S, Haruki N, Tatematsu Y, Konishi H, Mitsudomi T, Takahashi T, Takahashi T (2000) Frequent allelic imbalance suggests involvement of a tumor suppressor gene at 1p36 in the pathogenesis of human lung cancers. Genes Chromosomes Cancer 28(3):342–346. https://doi.org/10.1002/1098-2264(200007)28:3%3c342::aid-gcc13%3e3.0.co;2-a
Article
CAS
PubMed
Google Scholar
Yang Y, Ye Z, Zou Z, Xiao G, Luo G, Yang H (2014) Clinicopathological significance of RUNX3 gene hypermethylation in hepatocellular carcinoma. Tumour Biol 35(10):10333–10340. https://doi.org/10.1007/s13277-014-2329-7
Article
CAS
PubMed
Google Scholar
Rayess H, Wang MB, Srivatsan ES (2012) Cellular senescence and tumor suppressor gene p16. Int J Cancer 130(8):1715–1725. https://doi.org/10.1002/ijc.27316
Article
CAS
PubMed
Google Scholar
Li J, Poi MJ, Tsai MD (2011) Regulatory mechanisms of tumor suppressor P16 (INK4A) and their relevance to cancer. Biochemistry 50(25):5566–5582. https://doi.org/10.1021/bi200642e
Article
CAS
PubMed
Google Scholar
Tischoff I, Tannapfe A (2008) DNA methylation in hepatocellular carcinoma. World J Gastroenterol 14(11):1741–1748. https://doi.org/10.3748/wjg.14.1741
Article
CAS
PubMed
PubMed Central
Google Scholar
El-Bendary M, Nour D, Arafa M, Neamatallah M (2020) Methylation of tumour suppressor genes RUNX3, RASSF1A and E-Cadherin in HCV-related liver cirrhosis and hepatocellular carcinoma. Br J Biomed Sci 77(1):35–40. https://doi.org/10.1080/09674845.2019.1694123
Article
PubMed
Google Scholar
Seif AA, Aly HH, Elzoghby DM, Elbreedy AM, Lotfy M (2019) Aberrant p16 methylation as an early diagnostic marker in blood of hepatocellular carcinoma patients. Egypt J Med Hum Genet 20:27. https://doi.org/10.1186/s43042-019-0027-0
Article
Google Scholar
Charan J, Biswas T (2013) How to calculate sample size for different study designs in medical research? Indian J Psychol Med 35(2):121–126. https://doi.org/10.4103/0253-7176.116232
Article
PubMed
PubMed Central
Google Scholar
Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. https://doi.org/10.1002/hep.24199
Article
PubMed
Google Scholar
European Association for the Study of the Liver (2018) EASL Clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236. https://doi.org/10.1016/j.jhep.2018.03.019
Article
Google Scholar
Bialecki ES, Di Bisceglie AM (2005) Diagnosis of hepatocellular carcinoma. HPB (Oxford) 7(1):26–34. https://doi.org/10.1080/13651820410024049
Article
Google Scholar
Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 93(18):9821–9826. https://doi.org/10.1073/pnas.93.18.9821
Article
CAS
PubMed
PubMed Central
Google Scholar
Liu JB, Zhang YX, Zhou SH, Shi MX, Cai J, Liu Y, Chen KP, Qiang FL (2011) CpG island methylator phenotype in plasma is associated with hepatocellular carcinoma prognosis. World J Gastroenterol 17(42):4718–4724. https://doi.org/10.3748/wjg.v17.i42.4718
Article
CAS
PubMed
PubMed Central
Google Scholar
Ringelhan M, McKeating JA, Protzer U (2017) Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci 372(1732):20160274. https://doi.org/10.1098/rstb.2016.0274
Article
CAS
PubMed
Google Scholar
Herceg Z, Hainaut P (2007) Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol 1(1):26–41. https://doi.org/10.1016/j.molonc.2007.01.004
Article
CAS
PubMed
PubMed Central
Google Scholar
Liu M, Jiang L, Guan XY (2014) The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update. Protein Cell 5(9):673–691. https://doi.org/10.1007/s13238-014-0065-9
Article
CAS
PubMed
PubMed Central
Google Scholar
Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, Harris CC, Herman JG (2001) SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet 28(1):29–35. https://doi.org/10.1038/ng0501-29
Article
CAS
PubMed
Google Scholar
Chiba T, Yokosuka O, Fukai K, Hirasawa Y, Tada M, Mikata R, Imazeki F, Taniguchi H, Iwama A, Miyazaki M, Ochiai T, Saisho H (2005) Identification and investigation of methylated genes in hepatoma. Eur J Cancer 41(8):1185–1194. https://doi.org/10.1016/j.ejca.2005.02.014
Article
CAS
PubMed
Google Scholar
Fattovich G, Stroffolini T, Zagni I, Donato F (2004) Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127(5 Suppl 1):S35-50. https://doi.org/10.1053/j.gastro.2004.09.014
Article
PubMed
Google Scholar
Shaker MK, Abdella HM, Khalifa MO, El Dorry AK (2013) Epidemiological characteristics of hepatocellular carcinoma in Egypt: a retrospective analysis of 1313 cases. Liver Int 33(10):1601–1606. https://doi.org/10.1111/liv.12209
Article
CAS
PubMed
Google Scholar
El-Mougy FA, Youssef MM, Omran DA, Sharaf SA, El-Sayed HH, Rabie WA, Mohamed EA, Elghobary HA (2014) Aberrant p16INK4A methylation: relation to viral related chronic liver disease and hepatocellular carcinoma. South Asian J Cancer 3(1):1–4. https://doi.org/10.4103/2278-330X.126498
Article
PubMed
PubMed Central
Google Scholar
Teixeira AC, Mente ED, Cantao CAB, Sankarankutty AK, Souza FF, Motta TC, Monsignore L, Junior JE, Muglia VF, Abud DG, Peria FM, Silva OC, de Lourdes Candolo Martinelli A (2012) Clinical characteristics of 130 patients with hepatocellular carcinoma followed at a tertiary hospital from Brazil. World J Oncol 3(4):165–172. https://doi.org/10.4021/wjon549w
Article
PubMed
PubMed Central
Google Scholar
Darbari A, Sabin KM, Shapiro CN, Schwarz KB (2003) Epidemiology of primary hepatic malignancies in U.S. children. Hepatology 38(3):560–566. https://doi.org/10.1053/jhep.2003.50375
Article
PubMed
Google Scholar
Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H (2014) Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014:437971. https://doi.org/10.1155/2014/437971
Article
PubMed
PubMed Central
Google Scholar
Balogh J, Victor D, Asham EH, Burroughs SG, Boktour M, Saharia A, Li X, Ghobrial RM, Monsour HP Jr (2016) Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 3:41–53. https://doi.org/10.2147/JHC.S61146
Article
PubMed
PubMed Central
Google Scholar
Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL, Wright EC, Everson GT, Lindsay KL, Lok ASF, Lee WM, Morgan TR, Ghany MG, Gretch DR, HALT-C Trial Group (2005) Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C trial. J Hepatol 43(3):434–441. https://doi.org/10.1016/j.jhep.2005.03.019
Article
CAS
PubMed
Google Scholar
Tan SH, Ida H, Lau QC, Goh BC, Chieng W, Loh M, Ito Y (2007) Detection of promoter hypermethylation in serum samples of cancer patients by methylation-specific polymerase chain reaction for tumour suppressor genes including RUNX3. Oncol Rep 18:1225–1230. https://doi.org/10.3892/or.18.5.1225
Article
CAS
PubMed
Google Scholar
Sun G, Zhang C, Feng M, Liu W, Xie H, Qin Q, Zhao E, Wan L (2017) Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular carcinoma. Medicine (Baltimore) 96(41):e8279. https://doi.org/10.1097/MD.0000000000008279
Article
CAS
Google Scholar
Li QL, Ito K, Sakakura C, Fukamachi H, Ki Inoue, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y (2002) Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109(1):113–124. https://doi.org/10.1016/s0092-8674(02)00690-6
Article
CAS
PubMed
Google Scholar
Sun G, Zhang C, Feng M, Liu W, Xie H, Qin Q, Zhao E, Wan L (2017) Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular carcinoma. Medicine (Baltimore) 96(41):e8279. https://doi.org/10.1097/MD.0000000000008279
Article
CAS
Google Scholar
Park WS, Cho YG, Kim CJ, Song JH, Lee YS, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY (2005) Hypermethylation of the RUNX3 gene in hepatocellular carcinoma. Exp Mol Med 37(4):276–281. https://doi.org/10.1038/emm.2005.37
Article
CAS
PubMed
Google Scholar
Lee SH, Bae SC, Kim KW, Lee YM (2014) RUNX3 inhibits hypoxia-inducible factor-1α protein stability by interacting with prolyl hydroxylases in gastric cancer cells. Oncogene 33(11):1458–1467. https://doi.org/10.1038/onc.2013.76
Article
CAS
PubMed
Google Scholar
Wu HC, Wang Q, Yang HI, Tsai WY, Chen C, Santella RM (2012) Global DNA methylation levels in white blood cells as a biomarker for hepatocellular carcinoma risk: a nested case-control study. Carcinogenesis 33:1340–1345. https://doi.org/10.1093/carcin/bgs160
Article
CAS
PubMed
PubMed Central
Google Scholar
Bae SC, Choi JK (2004) Tumor suppressor activity of RUNX3. Oncogene 23:4336–4340. https://doi.org/10.1038/sj.onc.1207286
Article
CAS
PubMed
Google Scholar
Zaidi SK, Sullivan AJ, Wijnen AJV, Stein JL, Stein GS, Lian JB (2002) Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA 99:8048–8053. https://doi.org/10.1073/pnas.112664499
Article
CAS
PubMed
PubMed Central
Google Scholar
Lv X, Ye G, Zhang X, Huang T (2017) p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma, and p16 expression had a poor survival: a systematic meta-analysis (PRISMA). Medicine (Baltimore) 96(38):e8106. https://doi.org/10.1097/MD.0000000000008106
Article
CAS
Google Scholar
Piepkorn M (2000) Melanoma genetics: an update with focus on the CDKN2A (p16)/ARF tumor suppressors. J Am Acad Dermatol 42(5 pt 1):705–722. https://doi.org/10.1067/mjd.2000.104687
Article
CAS
PubMed
Google Scholar
Indovina P, Acquaviva A, De Falco G, Rizzo V, Onnis A, Luzzi A, Giorgi F, Hadjistilianou T, Toti P, Tomei V, Pentimalli F, Carugi A, Giordano A (2010) Downregulation and aberrant promoter methylation of p16INK4A: a possible novel heritable susceptibility marker to retinoblastoma. J Cell Physiol 223(1):143–150. https://doi.org/10.1002/jcp.22019
Article
CAS
PubMed
Google Scholar
Qu Z, Jiang Y, Li H, Yu DC, Ding YT (2015) Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance. Oncol Lett 10(4):2553–2558. https://doi.org/10.3892/ol.2015.3536
Article
CAS
PubMed
PubMed Central
Google Scholar