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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

The prognostic value of combined TGF-β1 and ELF in hepatocellular carcinoma

Authors: Fei Ji, Shun-Jun Fu, Shun-Li Shen, Long-Juan Zhang, Qing-Hua Cao, Shao-Qiang Li, Bao-Gang Peng, Li-Jian Liang, Yun-Peng Hua

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Tumor suppression of Transforming Growth Factor (TGF-β) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-β signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn’t been clarified. This study aimed to investigate whether measuring both TGF-β1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone.

Methods

TGF-β1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-β1/ELF expression and patients’ clinicopathologic factors was analyzed. The association between TGF-β1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses.

Results

The expression of TGF-β1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-β1. Patients with high TGF-β1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-β1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-β1 was more sensitive than that of either one alone.

Conclusions

TGF-β1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.
Literature
1.
EI-serag HB, Rudolph KL. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.CrossRef
2.
3.
4.
Ng KK, Lo CM, Liu CL, Poon RT, Chan SC, Fan ST. Survival analysis of patients with transplantable recurrent hepatocellular carcinoma: implications for salvage liver transplant. Arch Surg. 2008;143:68–74.CrossRefPubMed
5.
Kim DY, Paik YH, Ahn SH, Youn YJ, Choi JW, Kim JK, et al. PIVKA-II is a useful tumor marker for recurrent hepatocellular carcinoma after surgical resection. Oncology. 2007;72:52–7.CrossRefPubMed
6.
7.
Heldin CH, Landström M, Moustakas A. Mechanism of TGF-β signaling to growth arrest, apoptosis, and epithelialmesenchymal transition. Curr Opin Cell Biol. 2009;21:166–76.CrossRefPubMed
8.
Ikushima H, Miyazono K. Biology of transforming growth factor-β signaling. Curr Pharm Biotechnol. 2011;12:2099–107.CrossRefPubMed
9.
10.
11.
12.
Bierie B, Moses HL. Transforming growth factor beta (TGF-β) and inflammation in cancer. Cytokine Growth Factor Rev. 2010;21:49–59.CrossRefPubMed
13.
Kajdaniuk D, Marek B, Borgiel-Marek H, Kos-Kudła B. Transforming growth factorβ1 (TGFβ1) in physiology and pathology. Endokrynol Pol. 2013;64:384–96.CrossRefPubMed
14.
Zu X, Zhang Q, Gao R, Liu J, Zhong J, Wen G. Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: an update. Cell Tissue Res. 2012;347:73–84.CrossRefPubMed
15.
Malaguarnera G, Giordano M, Paladina I, Berretta M, Cappellani A, Malaguarnera M. Serum markers of hepatocellular carcinoma. Dig Dis Sci. 2010;55:2744–55.CrossRefPubMed
16.
Hua YP, Li SQ, Lai JM, Liang LJ, Peng BG, Liang HZ, et al. Changes in TGF-β/Smads signaling pathway in rats with chemical hepatocarcinogenesis. J South Med Univ. 2008;28:1848–52.
17.
Baek HJ, Lim SC, Kitisin K, Joqunoori W, Tang Y, Marshall MB, et al. Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology. 2008;48:1128–37.CrossRefPubMedPubMedCentral
18.
Thenappan A, Shukla V, Abdul Khalek FJ, Thenappan A, Shukla V, Abdul Khalek FJ, et al. Loss of transforming growth factor β adaptor protein β-2 spectrin leads to delayed liver regeneration in mice. Hepatology. 2011;53:1641–50.CrossRefPubMedPubMedCentral
19.
Wang Z, Song Y, Tu W, He X, Lin J, Liu F. β-2 spectrin is involved in hepatocyte proliferation through the interaction of TGFβ/Smad and PI3K/AKT signaling. Liver Int. 2012;32:1103–11.CrossRefPubMed
20.
Tang Y, Katuri V, Srinivasan R, Foqt F, Redman R, Anand G, et al. Transforming growth factor-beta suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis. Cancer Res. 2005;65:4228–37.CrossRefPubMed
21.
Mishra L, Katuri V, Evans S. The role of PRAJA and ELF in TGF-beta signaling and gastric cancer. Cancer Biol Ther. 2005;4:694–9.CrossRefPubMed
22.
Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, et al. Progenitor/ stem cells give rise to liver cancer due to aberrant TGF- beta and IL-6 signaling. Proc Natl Acad Sci U S A. 2008;105:2445–50.CrossRefPubMedPubMedCentral
23.
Kim SS, Shetty K, Katuri V, Kitisin K, Baek HJ, Tang Y, et al. TGF-beta signaling pathway inactivation and cell cycle deregulation in the development of gastric cancer: role of the beta-spectrin, ELF. Biochem Biophys Res Commun. 2006;344:1216–23.CrossRefPubMedPubMedCentral
24.
Kitisin K, Ganesan N, Tang Y, Joqunoori W, Volpe EA, Kim SS, et al. Disruption of transforming growth factor-beta signaling through beta-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation. Oncogene. 2007;26:7103–10.CrossRefPubMedPubMedCentral
25.
26.
Sobin LH, Wittekind C. UICC (International Union against Cancer) TNM classification of malignant tumors. 6th ed. New York: John Wiley; 2002. p. 1–264.
27.
Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed
28.
Weichert W, Röske A, Gekeler V, Beckers T, Ebert MP, Pross M, et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9:139–48.CrossRefPubMed
29.
Wu F, Liu SY, Tao YM, Ou DP, Fang F. Decreased expression of methyl methansulfonate and UV sensitive gene clone 81 is related to poor prognosis of patients with hepatocellular carcinoma. Cancer. 2008;112:2002–10.CrossRefPubMed
30.
Wu F, Yang LY, Li YF, Ou DP, Chen DP, Fan C. Novel role for epidermal growth factor-like domain 7 in metastasis of human hepatocellular carcinoma. Hepatology. 2009;50:1839–50.CrossRefPubMed
31.
Tripsianis G, Papadopoulou E, Romanidis K, Katotomichelakis M, Anagnostopoulos K, Kontomanolis E, et al. Overall Survival and Clinicopathological Characteristics of Patients with Breast Cancer in Relation to the Expression Pattern of HER-2, IL-6, TNF-α and TGF-β1. Asian Pac J Cancer Prev. 2013;14:6813–20.CrossRefPubMed
32.
de Kruijf EM, Dekker TJ, Hawinkels LJ, Putter H, Smit VT, Kroep JR, et al. The prognostic role of TGF-β signaling pathway in breast cancer patients. Ann Oncol. 2013;24:384–90.CrossRefPubMed
33.
Song S, Maru DM, Ajani JA, Chan CH, Honjo S, Lin HK, et al. Loss of TGF-β adaptor β2SP activates notch signaling and SOX9 expression in esophageal adenocarcinoma. Cancer Res. 2013;73:2159–69.CrossRefPubMedPubMedCentral
34.
Baek HJ, Pishvaian MJ, Tang Y, Kim TH, Yang S, Zouhairi ME, et al. Transforming growth factor-β adaptor, β2-spectrin, modulates cyclin dependent kinase 4 to reduce development of hepatocellular cancer. Hepatology. 2011;53:1676–84.CrossRefPubMedPubMedCentral
35.
Katuri V, Tang Y, Marshall B, Rashid A, Jogunoori W, Volpe EA, et al. Inactivation of ELF/TGF-beta signaling in human gastrointestinal cancer. Oncogene. 2005;24:8012–24.CrossRefPubMed
36.
Baek HJ, Kim SS, da Silva FM, Volpe EA, Evans S, Mishra B, et al. Inactivation of TGF-beta signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF. Biochem Biophys Res Commun. 2006;346:1150–7.CrossRefPubMed
37.
Li SX, Tang GS, Zhou DX, Pan YF, Tan YX, Zhang J, et al. Prognostic significance of cytoskeleton- associated membrane protein 4 and its palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma. Cancer. 2014;120:1520–31.CrossRefPubMed
Metadata
Title
The prognostic value of combined TGF-β1 and ELF in hepatocellular carcinoma
Authors
Fei Ji
Shun-Jun Fu
Shun-Li Shen
Long-Juan Zhang
Qing-Hua Cao
Shao-Qiang Li
Bao-Gang Peng
Li-Jian Liang
Yun-Peng Hua
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1127-y

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment

Case report

Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature

Research article

P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

Research article

Organized breast screening improves reattendance compared to physician referral: a case control study

Research article

A small molecular agent YL529 inhibits VEGF-D-induced lymphangiogenesis and metastasis in preclinical tumor models in addition to its known antitumor activities

Research article

Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits