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
Tumor Biology
Published in: Tumor Biology 10/2016

01-10-2016 | Original Article

Downregulated expression of DIXDC1 in hepatocellular carcinoma and its correlation with prognosis

Authors: Senjun Zhou, Jiliang Shen, Shuang Lin, Xiaolong Liu, Ming Xu, Liang Shi, Xianfa Wang, Xiujun Cai

Published in: Tumor Biology | Issue 10/2016

Login to get access

Abstract

Dishevelled-Axin domain containing 1 (DIXDC1) is a DIX (Dishevelled-Axin) domain possessing protein that acts as a positive regulator of the Wnt pathway. Although DIXDC1 has been investigated in several cancers, it has not yet been studied in human hepatocellular carcinoma (HCC). The purpose of the current study was to investigate the expression pattern of DIXDC1 and assess the clinical significance of DIXDC1 expression in HCC patients. Data containing three independent investigations from Oncomine database demonstrated that DIXDC1 mRNA was downregulated in HCC compared with matched non-cancerous tissues. Similar results were also obtained in 25 paired HCC tissues and corresponding non-cancerous tissues by qPCR and Western blot analysis. Additionally, another independent set of 140 pairs of HCC specimens was evaluated for DIXDC1 expression by IHC and demonstrated that reduced expression of DIXDC1 in 50.7 % (71/140) of HCC tissues was significantly correlated with tumor size (p = 0.024), tumor differentiation (p < 0.001), tumor thrombi (p = 0.019), TNM stage (p = 0.019), and BCLC stage (p = 0.008). Importantly, Kaplan–Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC patients and found that DIXDC1 protein expression was one of the independent prognostic factors for overall survival of HCC patients.
Appendix
Available only for authorised users
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics. CA Cancer J Clin. 2012;2015(65):87–108.
2.
3.
Pan HW, YH O, Peng SY, Liu SH, Lai PL, Lee PH, Sheu JC, Chen CL, Hsu HC. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer. 2003;98:119–27.CrossRefPubMed
4.
Goodwin JM, Svensson RU, Lou HJ, Winslow MM, Turk BE, Shaw RJ. An AMPK-independent signaling pathway downstream of the LKB1 tumor suppressor controls Snail1 and metastatic potential. Mol Cell. 2014;55:436–50.CrossRefPubMedPubMedCentral
5.
Shiomi K, Uchida H, Keino-Masu K, Masu M. Ccd1, a novel protein with a DIX domain, is a positive regulator in the Wnt signaling during zebrafish neural patterning. Curr Biol. 2003;13:73–7.CrossRefPubMed
6.
Singh KK, Ge X, Mao Y, Drane L, Meletis K, Samuels BA, Tsai LH. Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron. 2010;67:33–48.CrossRefPubMedPubMedCentral
7.
Kivimäe S, Martin PM, Kapfhamer D, Ruan Y, Heberlein U, Rubenstein JL, Cheyette BN. Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1. Transl Psychiatry. 2011;1:e43.CrossRefPubMedPubMedCentral
8.
Shiomi K, Kanemoto M, Keino-Masu K, Yoshida S, Soma K, Masu M. Identification and differential expression of multiple isoforms of mouse Coiled-coil-DIX1 (Ccd1), a positive regulatorof Wnt signaling. Mol Brain Res. 2005;135:169–80.CrossRefPubMed
9.
Wang X, Zheng L, Zeng Z, Zhou G, Chien J, Qian C, Vasmatzis G, Shridhar V, Chen L, Liu W. DIXDC1 isoform, l-DIXDC1, is a novel filamentous actin-binding protein. Biochem Biophys Res Commun. 2006;347:22–30.CrossRefPubMed
10.
Tan C, Qiao F, Wei P, Chi Y, Wang W, Ni S, Wang Q, Chen T, Sheng W, Du X, Wang L. DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis. Mol Carcinog. 2016;55:397–408.CrossRefPubMed
11.
Wang L, Tan C, Qiao F, Wang W, Jiang X, Lian P, Chang B, Sheng W. Upregulated expression of DIXDC1 in intestinal-type gastric carcinoma co-localization with β-catenin and correlation with poor prognosis. Cancer Cell Int. 2015;15:120.CrossRefPubMedPubMedCentral
12.
Xu Z, Liu D, Fan C, Luan L, Zhang X, Wang E. DIXDC1 increases the invasion and migration ability of non-small-cell lung cancer cells via the PI3K-AKT-AP-1 pathway. Mol Carcinog. 2014;53:917–25.CrossRefPubMed
13.
Wang L, Cao XX, Chen Q, Zhu TF, Zhu HG, Zheng L. DIXDC1 targets p21 and cyclin D1 via PI3K pathway activation to promote colon cancer cell proliferation. Cancer Sci. 2009;100:1801–8.CrossRefPubMed
14.
Wang L, Li H, Chen Q, Zhu T, Zhu H, Zheng L. Wnt signaling stabilizes the DIXDC1 protein through decreased ubiquitin-dependent degradation. Cancer Sci. 2010;101:700–6.CrossRefPubMed
15.
Edge SB, Byrd DR, Compton CC et al (eds) (2009) AJCC cancer staging manual, 7th edn. Springer, New York
16.
Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698–711.CrossRefPubMed
17.
Tang L, Tan YX, Jiang BG, Pan YF, Li SX, Yang GZ, et al. The prognostic significance and therapeutic potential of hedgehog signaling in intrahepatic cholangiocellular carcinoma. Clin Cancer Res. 2013;19:2014–24.CrossRefPubMed
18.
Luo RZ, Cai PQ, Li M, Fu J, Zhang ZY, Chen JW, Cao Y, Yun JP, Xie D, Cai MY. Decreased expression of PTPN12 correlates with tumor recurrence and poor survival of patients with hepatocellular carcinoma. PLoS One. 2014;9(1):e85592.CrossRefPubMedPubMedCentral
19.
Llovet JM1, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX,et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008; 100: 698–711.
20.
Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. 2006;12:410–6.CrossRefPubMed
21.
22.
Liu YT, Dan QJ, Wang J, Feng Y, Chen L, Liang J, Li Q, Lin SC, Wang ZX, Wu JW. Molecular basis of Wnt activation via the DIX domain protein Ccd1. J Biol Chem 2011; 286: 8597–8608.
23.
Wong CK, Luo W, Deng Y, Zou H, Ye Z, Lin SC. The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by axin and dishevelled through distinct mechanisms. J Biol Chem. 2004;279:39366–73.CrossRefPubMed
24.
Wu Y, Jing X, Ma X, Wu Y, Ding X, Fan W, Fan M. DIXDC1 co-localizes and interacts with gamma-tubulin in HEK293 cells. Cell Biol Int. 2009;33:697–701.CrossRefPubMed
25.
Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology. 2002;35:519–24.CrossRefPubMed
26.
Ajay D. Staging of hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(Suppl 3):S74–9.
27.
Aravalli RN, Cressman EN, Steer CJ. Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch Toxicol. 2013;87:227–47.CrossRefPubMed
28.
Funasaka T, Hogan V, Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer. Cancer Res. 2009;69:5349–56.CrossRefPubMedPubMedCentral
29.
Lee BY, Timpson P, Horvath LG, Daly RJ. FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 2015;146:132–49.CrossRefPubMed
30.
Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9.CrossRefPubMed
31.
A Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodés J. EASL panel of experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–30.CrossRefPubMed
Metadata
Title
Downregulated expression of DIXDC1 in hepatocellular carcinoma and its correlation with prognosis
Authors
Senjun Zhou
Jiliang Shen
Shuang Lin
Xiaolong Liu
Ming Xu
Liang Shi
Xianfa Wang
Xiujun Cai
Publication date
01-10-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 10/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5213-9

Other articles of this Issue 10/2016

Tumor Biology 10/2016 Go to the issue

Original Article

Violacein induces death of RAS-mutated metastatic melanoma by impairing autophagy process

Review

Molecular mechanisms of action of quercetin in cancer: recent advances

Original Article

MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer

Original Article

Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer

Original Article

Overall survival of cancer patients with serum lactate dehydrogenase greater than 1000 IU/L

Review

Peptide receptor radionuclide therapy: focus on bronchial neuroendocrine tumors
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