Skip to main content
Top
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma

Authors: Chenghua Zhang, Ran Xia, Bo Zhang, Haibo Wang

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Earlier diagnosis is beneficial for the prognosis of hepatocellular carcinoma (HCC). Alpha fetoprotein (AFP) is the most widely used biomarker for HCC, but its sensitivity and specificity are only 60 and 90%, respectively. Therefore, it is of great clinical significance to identify early prognostic biomarkers for HCC, especially a blood-based biomarker as it offers several advantages over tissue-based biomarkers. Trefoil factor 3 (TFF3), a novel secretory protein, was over-expressed in HCC tissues, indicating it might be a blood-based biomarker for HCC. In addition, circulating microRNAs have been investigated as biomarkers for HCC, indicating that miR-7-5p and miR-203a-3p, which are reported or predicted to target TFF3, also hold promise as blood-based biomarkers for HCC.

Methods

We enrolled 43 patients who were firstly diagnosed HCC and matched 47 control subjects without HCC. The levels of TFF3, miR-7-5p and miR-203a-3p were tested in the plasma of HCC patients. Moreover, we assayed the correlation of TFF3 with its related micro RNAs, miR-7-5p and miR-203a-3p, and evaluated their predictive powers for HCC.

Results

Decrease of TFF3 was associated with increase of miR-203a-3p in the plasma of HCC patients and they displayed potent predictive powers for HCC diagnosis. However, there was no significant change of plasma miR-7-5p between HCC and control group.

Conclusion

Decrease of TFF3 correlated with increase of miR-203a-3p in the plasma of HCC patients and they could be additional biomarkers to improve sensitivity and specificity in the diagnosis of HCC.
Literature
1.
go back to reference Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRef Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRef
2.
go back to reference Ji J, Wang H, Li Y, et al. Diagnostic evaluation of des-gamma-carboxy prothrombin versus α-fetoprotein for hepatitis B virus-related hepatocellular carcinoma in China: a large-scale, multicentre study. PLoS One. 2016;11(4):e0153227.CrossRef Ji J, Wang H, Li Y, et al. Diagnostic evaluation of des-gamma-carboxy prothrombin versus α-fetoprotein for hepatitis B virus-related hepatocellular carcinoma in China: a large-scale, multicentre study. PLoS One. 2016;11(4):e0153227.CrossRef
3.
go back to reference Ganepola GAP, Nizin J, Rutledge JR, et al. Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer. World J Gastrointest Oncol. 2014;6(4):83–97.CrossRef Ganepola GAP, Nizin J, Rutledge JR, et al. Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer. World J Gastrointest Oncol. 2014;6(4):83–97.CrossRef
4.
go back to reference Baus-Loncar M, Giraud AS. Trefoil factors. Cell Mol Life Sci CMLS. 2005;62(24):2921–31.CrossRef Baus-Loncar M, Giraud AS. Trefoil factors. Cell Mol Life Sci CMLS. 2005;62(24):2921–31.CrossRef
5.
go back to reference Chen X, Yamamoto M, Fujii K, et al. Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and noncirrhotic conditions. Cancer Sci. 2015;23:12700. Chen X, Yamamoto M, Fujii K, et al. Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and noncirrhotic conditions. Cancer Sci. 2015;23:12700.
6.
go back to reference Franke TF. PI3K/Akt: getting it right matters. Oncogene. 2008;27:6473–88.CrossRef Franke TF. PI3K/Akt: getting it right matters. Oncogene. 2008;27:6473–88.CrossRef
7.
go back to reference Sun Q, Zhang Y, Liu F, Zhao X, Yang X. Identification of candidate biomarkers for hepatocellular carcinoma through pre-cancerous expression analysis in an HBx transgenic mouse. Cancer Biol Ther. 2007;6:1532–8.CrossRef Sun Q, Zhang Y, Liu F, Zhao X, Yang X. Identification of candidate biomarkers for hepatocellular carcinoma through pre-cancerous expression analysis in an HBx transgenic mouse. Cancer Biol Ther. 2007;6:1532–8.CrossRef
8.
go back to reference Sierzega M, Kaczor M, Kolodziejczyk P, et al. Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331. Br J Cancer. 2017;117(2):266–73.CrossRef Sierzega M, Kaczor M, Kolodziejczyk P, et al. Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331. Br J Cancer. 2017;117(2):266–73.CrossRef
9.
go back to reference Wulfken LM, Moritz R, Ohlmann C, et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 2011;6(9):e25787.CrossRef Wulfken LM, Moritz R, Ohlmann C, et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 2011;6(9):e25787.CrossRef
10.
go back to reference Pritchard CC, Kroh E, Wood B, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res. 2011;5:492–7.CrossRef Pritchard CC, Kroh E, Wood B, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res. 2011;5:492–7.CrossRef
11.
go back to reference Fei Y, Hou J, Xuan W, et al. The relationship of plasma miR-503 and coronary collateral circulation in patients with coronary artery disease. Life Sci. 2018;207:145–51.CrossRef Fei Y, Hou J, Xuan W, et al. The relationship of plasma miR-503 and coronary collateral circulation in patients with coronary artery disease. Life Sci. 2018;207:145–51.CrossRef
12.
go back to reference Kannan N, Kang J, Kong X, et al. Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Neoplasia. 2010;12:1041–53.CrossRef Kannan N, Kang J, Kong X, et al. Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Neoplasia. 2010;12:1041–53.CrossRef
13.
go back to reference Garraway IP, Seligson D, Said J, Horvath S, Reiter RE. Trefoil factor 3 is overexpressed in human prostate cancer. Prostate. 2004;61:209–14.CrossRef Garraway IP, Seligson D, Said J, Horvath S, Reiter RE. Trefoil factor 3 is overexpressed in human prostate cancer. Prostate. 2004;61:209–14.CrossRef
14.
go back to reference Khoury T, Chadha K, Javle M, et al. Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma. Int J Gastrointest Cancer. 2005;35:171–7.CrossRef Khoury T, Chadha K, Javle M, et al. Expression of intestinal trefoil factor (TFF-3) in hepatocellular carcinoma. Int J Gastrointest Cancer. 2005;35:171–7.CrossRef
15.
go back to reference Shukla A, Gupta P, Singh R, et al. Glycolytic inhibitor 2-deoxy-d-glucose activates migration and invasion in glioblastoma cells through modulation of the miR-7-5p/TFF3 signaling pathway. Biochem Biophys Res Commun. 2018;499(4):829–35.CrossRef Shukla A, Gupta P, Singh R, et al. Glycolytic inhibitor 2-deoxy-d-glucose activates migration and invasion in glioblastoma cells through modulation of the miR-7-5p/TFF3 signaling pathway. Biochem Biophys Res Commun. 2018;499(4):829–35.CrossRef
16.
go back to reference Shang YL, Qian YB. Clinical significance of expression of trefoil factor 3 in hepatocellular carcinoma. World Chinese J Digestol. 2014;22(8):1141-1145.CrossRef Shang YL, Qian YB. Clinical significance of expression of trefoil factor 3 in hepatocellular carcinoma. World Chinese J Digestol. 2014;22(8):1141-1145.CrossRef
17.
go back to reference Lau WH, Pandey V, Kong X, et al. Trefoil factor-3 (TFF3) stimulates de novo angiogenesis in mammary carcinoma both directly and indirectly via IL-8/CXCR2. PLoS One. 2015;10(11):e0141947.CrossRef Lau WH, Pandey V, Kong X, et al. Trefoil factor-3 (TFF3) stimulates de novo angiogenesis in mammary carcinoma both directly and indirectly via IL-8/CXCR2. PLoS One. 2015;10(11):e0141947.CrossRef
18.
go back to reference Guleng B, Han J, Yang JQ, et al. TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells. Mol Biol Rep. 2012;39(4):4127–34.CrossRef Guleng B, Han J, Yang JQ, et al. TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells. Mol Biol Rep. 2012;39(4):4127–34.CrossRef
19.
go back to reference Chan MW, Chan VY, Leung WK, et al. Anti-sense trefoil factor family-3 (intestinal trefoil factor) inhibits cell growth and induces chemosensitivity to adriamycin in human gastric cancer cells. Life Sci. 2005;76:2581–92.CrossRef Chan MW, Chan VY, Leung WK, et al. Anti-sense trefoil factor family-3 (intestinal trefoil factor) inhibits cell growth and induces chemosensitivity to adriamycin in human gastric cancer cells. Life Sci. 2005;76:2581–92.CrossRef
20.
go back to reference You ML, Chen YJ, Chong QY, et al. Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent. Oncotarget. 2017;8(24):39323–44.CrossRef You ML, Chen YJ, Chong QY, et al. Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent. Oncotarget. 2017;8(24):39323–44.CrossRef
21.
go back to reference Zhao S, Han J, Zheng L, et al. Microrna-203 regulates growth and metastasis of breast cancer. Cell Physiol Biochem. 2015;37(1):35–42.CrossRef Zhao S, Han J, Zheng L, et al. Microrna-203 regulates growth and metastasis of breast cancer. Cell Physiol Biochem. 2015;37(1):35–42.CrossRef
22.
go back to reference Deng B, Wang B, Fang J, et al. MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2. Sci Rep. 2016;6:28301.CrossRef Deng B, Wang B, Fang J, et al. MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2. Sci Rep. 2016;6:28301.CrossRef
23.
go back to reference Lohcharoenkal W, Harada M, Lovén J, et al. MicroRNA-203 inversely correlates with differentiation grade, targets c-MYC, and functions as a tumor suppressor in cSCC. J Investig Dermatol. 2016;136(12):2485–94.CrossRef Lohcharoenkal W, Harada M, Lovén J, et al. MicroRNA-203 inversely correlates with differentiation grade, targets c-MYC, and functions as a tumor suppressor in cSCC. J Investig Dermatol. 2016;136(12):2485–94.CrossRef
24.
go back to reference Zhu X, Er K, Mao C, et al. miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 2013;32(1):64–73.CrossRef Zhu X, Er K, Mao C, et al. miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 2013;32(1):64–73.CrossRef
25.
go back to reference Xu J, Zhu X, Wu L, et al. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway. Liver Int. 2012;32:752–60.CrossRef Xu J, Zhu X, Wu L, et al. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway. Liver Int. 2012;32:752–60.CrossRef
26.
go back to reference Zhu J, Zheng Z, Wang J, et al. Different miRNA expression profiles between human breast cancer tumors and serum. Front Genet. 2014;5:149.CrossRef Zhu J, Zheng Z, Wang J, et al. Different miRNA expression profiles between human breast cancer tumors and serum. Front Genet. 2014;5:149.CrossRef
27.
go back to reference Zhu YQ, Tan XD. TFF3 modulates NF-κB and a novel negative regulatory molecule of NF-κB in intestinal epithelial cells via a mechanism distinct from TNF-α. Am J Phys Cell Phys. 2005;289(5):C1085–93.CrossRef Zhu YQ, Tan XD. TFF3 modulates NF-κB and a novel negative regulatory molecule of NF-κB in intestinal epithelial cells via a mechanism distinct from TNF-α. Am J Phys Cell Phys. 2005;289(5):C1085–93.CrossRef
28.
go back to reference Loos M, De Creus A, Thim L, Remaut E, Rottiers P. Murine trefoil factor 3 does not directly modulate LPS-mediated dendritic cell function. Scand J Immunol. 2007;66(1):35–42.CrossRef Loos M, De Creus A, Thim L, Remaut E, Rottiers P. Murine trefoil factor 3 does not directly modulate LPS-mediated dendritic cell function. Scand J Immunol. 2007;66(1):35–42.CrossRef
29.
go back to reference Wei J, Huang X, Zhang Z, et al. MyD88 as a target of microRNA-203 in regulation of lipopolysaccharide or Bacille Calmette-Guerin induced inflammatory response of macrophage RAW264. 7 cells. Mol Immunol. 2013;55(3):303–9.CrossRef Wei J, Huang X, Zhang Z, et al. MyD88 as a target of microRNA-203 in regulation of lipopolysaccharide or Bacille Calmette-Guerin induced inflammatory response of macrophage RAW264. 7 cells. Mol Immunol. 2013;55(3):303–9.CrossRef
30.
go back to reference Zhou M, Chen J, Zhou L, et al. Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell Immunol. 2014;292(1–2):65–9.CrossRef Zhou M, Chen J, Zhou L, et al. Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell Immunol. 2014;292(1–2):65–9.CrossRef
31.
go back to reference Xu T, Chu Q, Cui J, Zhao X. The inducible microRNA-203 in fish represses the inflammatory responses to gram-negative bacteria by targeting IL-1 receptor-associated kinase 4. J Biol Chem. 2018;293(4):1386–96.CrossRef Xu T, Chu Q, Cui J, Zhao X. The inducible microRNA-203 in fish represses the inflammatory responses to gram-negative bacteria by targeting IL-1 receptor-associated kinase 4. J Biol Chem. 2018;293(4):1386–96.CrossRef
32.
go back to reference Guo J, Sun M, Teng X, et al. MicroRNA-7-5p regulates the expression of TFF3 in inflammatory bowel disease. Mol Med Rep. 2017;16(2):1200–6.CrossRef Guo J, Sun M, Teng X, et al. MicroRNA-7-5p regulates the expression of TFF3 in inflammatory bowel disease. Mol Med Rep. 2017;16(2):1200–6.CrossRef
33.
go back to reference Tarek M, Louka ML, Khairy E, et al. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma. Tumor Biol. 2017;39(5):1010428317698372.CrossRef Tarek M, Louka ML, Khairy E, et al. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma. Tumor Biol. 2017;39(5):1010428317698372.CrossRef
34.
go back to reference Wu W, Liu S, Liang Y, et al. MiR-7 inhibits progression of hepatocarcinoma by targeting KLF-4 and promises a novel diagnostic biomarker. Cancer Cell Int. 2017;17(1):31.CrossRef Wu W, Liu S, Liang Y, et al. MiR-7 inhibits progression of hepatocarcinoma by targeting KLF-4 and promises a novel diagnostic biomarker. Cancer Cell Int. 2017;17(1):31.CrossRef
Metadata
Title
The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma
Authors
Chenghua Zhang
Ran Xia
Bo Zhang
Haibo Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5017-y

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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