Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Diagnosis & Therapy
Published in: Molecular Diagnosis & Therapy 3/2016

01-06-2016 | Original Research Article

Evaluation of Circulatory RNA-Based Biomarker Panel in Hepatocellular Carcinoma

Authors: Ahmed Hassan Fawzi El-Tawdi, Marwa Matboli, Hanan Hussein Shehata, Fathy Tash, Nashwa El-Khazragy, Ahmed El-Sayed Mansour Azazy, Omar Abdel-Rahman

Published in: Molecular Diagnosis & Therapy | Issue 3/2016

Login to get access

Abstract

Background

The circulating transcriptome (coding and non-coding) plays a critical role in cancer. Novel accurate strategies for early detection of hepatocellular carcinoma (HCC) are strongly needed.

Patients and Methods

We chose an HCC-specific RNA-based biomarker panel based on the integration of differential lysosomal-associated membrane protein 2 (LAMP2) gene expression with its selected epigenetic regulators using bioinformatic methods. This was followed by RT-qPCR validation in serum of 78 patients with HCC, 36 patients with chronic hepatitis C (CHC) infection and 44 healthy volunteers. We used risk-score analysis to evaluate the diagnostic efficacy of the serum profiling system. Moreover, in twenty of the 78 HCC cases involved in the study we examined the expression of RNA-based biomarker panel in both HCC and adjacent non-tumor tissues and assessed their correlation with the serum level of this panel.

Results

The four ribonucleic acid (RNA)-based biomarker panel [long non-coding RNA-C terminal binding protein, androgen responsive (lncRNA–CTBP), microRNA-16-2 (miR-16-2), microRNA-21-5-P (miR-21-5p) and LAMP2], had high sensitivity and specificity for discriminating HCC from healthy controls and also from CHC patients. Among these four RNAs, serum miR-16-2 and miR-21-5p were independent prognostic factors.

Conclusion

The circulatory RNA-based biomarker panel can serve as a potential biomarker for HCC diagnosis and prognosis.
Appendix
Available only for authorised users
Literature
1.
2.
National Cancer Registry of Egypt. Magnitude of hepatocellular carcinoma in Egypt. 2010; [updated 2010 August 6].
3.
Abdelgawad IA, Mossallam GI, Radwan NH, Elzawahry HM, Elhifnawy NM. Can Glypican3 be diagnostic for early hepatocellular carcinoma among Egyptian patients? Asian Pac J Cancer Prev. 2013;14(12):7345–9.CrossRefPubMed
4.
Stewart BW, Wild CP. In liver cancer, World Cancer Report 2014. IARC; 2014.
5.
He Y, Meng XM, Huang C, Wu BM, Zhang L, Lv XW, et al. Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Lett. 2014;344(1):20–7.CrossRefPubMed
6.
Papandreou I, Lim AL, Laderoute K, Denko NC. Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death Differ. 2008;15(10):1572–81.CrossRefPubMed
7.
8.
Dalby KN, Tekedereli I, Lopez-Berestein G, Ozpolat B. Targeting prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy. 2010;6:322–9.CrossRefPubMedPubMedCentral
9.
Chen JW, Murphy TL, Willingtham MC, Pastan I, August JT. Identification of two lysosomal membrane glycoproteins. J Cell Biol. 1985;101:85–95.CrossRefPubMed
10.
Lee N, Wang WC, Fukuda M. Granulocytic differentiation of HL-60 cells is associated with increase of poly-N-acetyllactosamine in Asn-linked oligosaccharides attached to human lysosomal membrane glycoproteins. J Biol Chem. 1990;265:20476–87.PubMed
11.
Tsunedomi R, Iizuka N, Yamada-Okabe H, Tamesa T, Okada T, Sakamoto K, Takashima M, Hamaguchi T, Miyamoto T, Uchimura S, Hamamoto Y, Yamada M, Oka M. Identification of ID2 associated with invasion of hepatitis C virus-related hepatocellular carcinoma by gene expression profile. Int J Oncol. 2006;29(6):1445–51.PubMed
12.
Li Y, Li Y, Tang R, Xu H, Qiu M, Chen Q, Chen J, Fu Z, Ying K, Xie Y, Mao Y. Discovery and analysis of hepatocellular carcinoma genes using cDNA microarrays. J Cancer Res ClinOncol. 2002;128(7):369–79.CrossRef
13.
He M, Qin H, Poon TC, Sze SC, Ding X, Co NN, Ngai SM, Chan TF, Wong N. Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs. Carcinogenesis. 2015;36(9):1008–18.CrossRefPubMed
14.
15.
Li JH, Liu S, Zhou H, Qu LH, Yang JH. StarBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42:D92–7.CrossRefPubMedPubMedCentral
16.
Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147:358–69.CrossRefPubMedPubMedCentral
17.
Wang P, Ning S, Zhang Y, Li R, Ye J, Zhao Z, Zhi H, Wang T, Guo Z, Li X. Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer. Nucleic Acids Res. 2015;43(7):3478–89.CrossRefPubMedPubMedCentral
18.
Li H, Yu B, Li J, Su L, Yan M, Zhu Z, et al. Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget. 2014;5:2318–29.CrossRefPubMedPubMedCentral
19.
Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, et al. Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 2010;31:350–8.CrossRefPubMed
20.
Reis EM, Nakaya HI, Louro R, Canavez FC, Flatschart AV, Almeida GT, et al. Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer. Oncogene. 2004;23:6684–92.CrossRefPubMed
21.
22.
Ezzat H, Lotfy AM, Alalfy MN, El-Taher SM, Mokhtar A, Mohamed SA, El-Senosy FM. The significance of circulating MicroRNA-122 as a non invasive diagnostic marker of liver injury in Egyptian chronic hepatitis C virus infected and cirrhotic patients with and without hepatocellular carcinoma. Clin Med Diagnost. 2014;4(1):1–8.CrossRef
23.
24.
Zhao X, Zhen Y, Li G, Li D, Zhao Y, Wu Y, Robson S, He L, Xu Y, Miao R, Zhao HT. The role and clinical implications of microRNAs in hepatocellular carcinoma. Sci China Life Sci. 2012;55(10):906–19.CrossRefPubMed
25.
Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg 1964;1:1–85 [Medline].
26.
Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–9.CrossRefPubMed
27.
Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRefPubMed
28.
29.
Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 2012;40:D109–14.CrossRefPubMedPubMedCentral
30.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta deltaC(T)) method. Methods. 2001;25:402–8.CrossRefPubMed
31.
Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck C, Denk H, Schroeder R, Trauner M, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132:330–42.CrossRefPubMed
32.
Saitoh O, Wang WC, Lotan R, Fukuda M. Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem. 1992;267:5700–11.PubMed
33.
Künzli BM, Berberat PO, Zhu ZW, Martignoni M, Kleeff J, Tempia-Caliera AA, Fukuda M, Zimmermann A, Friess H, Büchler MW. Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma. Cancer. 2002;94(1):228–39.CrossRefPubMed
34.
Kaji H, Ocho M, Togayachi A, Kuno A, Sogabe M, Ohkura T, Nozaki H, Angata T, Chiba Y, Ozaki H, Hirabayashi J, Tanaka Y, Mizokami M, Ikehara Y, Narimatsu H. Glycoproteomic discovery of serological biomarker candidates for HCV/HBV infection-associated liver fibrosis and hepatocellular carcinoma. J Proteome Res. 2013;12(6):2630–40.CrossRefPubMed
35.
Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67:6092–9.CrossRefPubMed
36.
37.
El-Abd NE, Fawzy NA, El-Sheikh SM, Soliman ME. Circulating miRNA-122, miRNA-199a, and miRNA-16 as biomarkers for early detection of hepatocellular carcinoma in egyptian patients with chronic hepatitis C virus infection. Mol Diagn Ther. 2015;19(4):213–20.CrossRefPubMed
38.
Ge W, Yu DC, Li QG, Chen X, Zhang CY, Ding YT. Expression of serum miR-16, let-7f, and miR-21 in patients with hepatocellular carcinoma and their clinical significances. Clin Lab. 2014;60(3):427–34.PubMed
39.
Qu KZ, Zhang K, Li H, Afdhal NH, Albitar M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol. 2011;45(4):355–60.CrossRefPubMed
40.
41.
Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.PubMedPubMedCentral
42.
Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75.CrossRefPubMed
43.
Xu J, Wu C, Che X, Wang L, Yu D, 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.CrossRefPubMed
44.
Fornari F, Ferracin M, Trerè D, Milazzo M, Marinelli S, Galassi M, Venerandi L, Pollutri D, Patrizi C, Borghi A, Foschi FG, Stefanini GF, Negrini M, Bolondi L, Gramantieri L. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC. PLoS One. 2015;10(10):e0141448. doi:10.​1371/​journal.​pone.​0141448 (eCollection 2015).
45.
He C, Dong X, Zhai B, Jiang X, Dong D, Li B, Jiang H, Xu S, Sun X. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget. 2015;6(30):28867–81.PubMedPubMedCentral
46.
Yun JS, Gardner K. C-terminal binding protein: a molecular link between metabolic imbalance and epigenetic regulation in breast cancer. Int J Cell Biol. 2013;2013:647975.
47.
Di LJ, Byun JS, Wong MM, Wakano C, Taylor T, Bilke S, et al. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nat Commun. 2013;4:1449.CrossRefPubMedPubMedCentral
48.
Paliwal S, Pande S, Kovi RC, Sharpless NE, Bardeesy N, Grossman SR. Targeting of C-terminal binding protein (CtBP) by ARF results in p53-independent apoptosis. Mol Cell Biol. 2006;26(6):2360–72.CrossRefPubMedPubMedCentral
49.
Takayama K, Horie-Inoue K, Katayama S, Suzuki T, Tsutsumi S, Ikeda K, Urano T, Fujimura T, Takagi K, Takahashi S, Homma Y, Ouchi Y, Aburatani H, Hayashizaki Y, Inoue S. Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. EMBO J. 2013;32(12):1665–80.CrossRefPubMedPubMedCentral
50.
Abdel-Hamid M, Shaker OG, Ellakwa DE, Abdel-Maksoud EF. Detection of BCL2 polymorphism in patient with hepatocellular carcinoma. Am J Cancer Prevention. 2015;3(2):27–34. doi:10.​12691/​ajcp-3-2-2.
51.
Paul SB, Gulati MS, Sreenivas V, Madan K, Gupta AK, Mukhopadhyay S, Acharya SK. Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein. Oncology. 2007;72(Suppl 1):117–23.CrossRefPubMed
Metadata
Title
Evaluation of Circulatory RNA-Based Biomarker Panel in Hepatocellular Carcinoma
Authors
Ahmed Hassan Fawzi El-Tawdi
Marwa Matboli
Hanan Hussein Shehata
Fathy Tash
Nashwa El-Khazragy
Ahmed El-Sayed Mansour Azazy
Omar Abdel-Rahman
Publication date
01-06-2016
Publisher
Springer International Publishing
Published in
Molecular Diagnosis & Therapy / Issue 3/2016
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI
https://doi.org/10.1007/s40291-016-0200-9

Other articles of this Issue 3/2016

Molecular Diagnosis & Therapy 3/2016 Go to the issue

Original Research Article

Novel Approach for Clinical Validation of the cobas KRAS Mutation Test in Advanced Colorectal Cancer

Original Research Article

Association Between Early PSA Increase and Clinical Outcome in Patients Treated with Enzalutamide for Metastatic Castration Resistant Prostate Cancer

Short Communication

Molecular Characterization of Intermediate Susceptible Typhoidal Salmonella to Ciprofloxacin, and its Impact

Short Communication

A Pharmacogenetic Study of Psoriasis Risk Variants in a Greek Population and Prediction of Responses to Anti-TNF-α and Anti-IL-12/23 Agents

Original Research Article

Enhancement of PCR Detection Limit by Single-Tube Restriction Endonuclease-PCR (RE-PCR)

Original Research Article

Mutation Yield of a 34-Gene Solid Tumor Panel in Community-Based Tumor Samples
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits