TITLE

Role of Leukocyte Cell-Derived Chemotaxin 2 as a Biomarker in Hepatocellular Carcinoma

AUTHOR(S)
Okabe, Hirohisa; Delgado, Evan; Lee, Jung Min; Yang, Jing; Kinoshita, Hiroki; Hayashi, Hiromitsu; Tsung, Allan; Behari, Jaideep; Beppu, Toru; Baba, Hideo; Monga, Satdarshan P.
PUB. DATE
June 2014
SOURCE
PLoS ONE;Jun2014, Vol. 9 Issue 6, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
We sought to identify a secreted biomarker for β-catenin activation commonly seen in hepatocellular carcinoma (HCC). By examination of our previously published genearray of hepatocyte-specific β-catenin knockout (KO) livers, we identified secreted factors whose expression may be β-catenin-dependent. We verified expression and secretion of the leading factor in HCC cells transfected with mutated (Hep3BS33Y)-β-catenin. Serum levels of biomarker were next investigated in a mouse model of HCC with β-catenin gene (Ctnnb1) mutations and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2) expression was decreased in KO livers. Hep3BS33Y expressed and secreted more LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations showed significantly higher serum LECT2 levels. However patients with CTNNB1 mutations showed LECT2 levels of 54.28±22.32 ng/mL (Mean ± SD; n = 8) that were insignificantly different from patients with non-neoplastic chronic liver disease (32.8±21.1 ng/mL; n = 15) or healthy volunteers (33.2±7.2 ng/mL; n = 11). Intriguingly, patients without β-catenin mutations showed significantly higher serum LECT2 levels (54.26 ± 22.25 ng/mL; n = 46). While β-catenin activation was evident in a subset of non-mutant β-catenin HCC group with high LECT2 expression, serum LECT2 was unequivocally similar between β-catenin-active and -normal group. Further analysis showed that LECT2 levels greater than 50 ng/ml diagnosed HCC in patients irrespective of β-catenin mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus, LECT2 is regulated by β-catenin in HCC in both mice and men, but serum LECT2 reflects β-catenin activity only in mice. Serum LECT2 could be a potential biomarker of HCC in patients.
ACCESSION #
96859271

 

Related Articles

  • 14-3-3ε Overexpression Contributes to Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma. Liu, Tzu-An; Jan, Yee-Jee; Ko, Bor-Sheng; Liang, Shu-Man; Chen, Shyh-Chang; Wang, John; Hsu, Chiun; Wu, Yao-Ming; Liou, Jun-Yang // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    Background: 14-3-3ε is implicated in regulating tumor progression, including hepatocellular carcinoma (HCC). Our earlier study indicated that elevated 14-3-3ε expression is significantly associated with higher risk of metastasis and lower survival rates of HCC patients. However, the...

  • Gene-expression signature in liver tissue correlated with survival in hepatocellular carcinoma.  // Hem/Onc Today;11/10/2008, Vol. 9 Issue 20, p27 

    The article focuses on a study which examined tissues from 307 patients with hepatocellular carcinoma. The study found a correlation between survival and a reproducible gene-expression signature in liver tissue adjacent to the tumor. The study concluded that it is feasible to use formalin-fixed,...

  • Diagnostic Value of SFRP1 as a Favorable Predictive and Prognostic Biomarker in Patients with Prostate Cancer. Zheng, Lei; Sun, Dongchen; Fan, Wentao; Zhang, Zhiwei; Li, Quanlin; Jiang, Tao // PLoS ONE;Feb2015, Vol. 10 Issue 2, p1 

    Growing genetic and molecular biological evidence suggests that the disruption of balance between Secreted Frizzled-Related Protein-1 (SFRP1) and β-catenin plays an important role in the initiation and development of multiple cancers. The aim of this study was to examine whether the...

  • Discretization Provides a Conceptually Simple Tool to Build Expression Networks. Vass, J. Keith; Higham, Desmond J.; Mudaliar, Manikhandan A. V.; Xuerong Mao; Crowther, Daniel J. // PLoS ONE;2011, Vol. 6 Issue 4, p1 

    Biomarker identification, using network methods, depends on finding regular co-expression patterns; the overall connectivity is of greater importance than any single relationship. A second requirement is a simple algorithm for ranking patients on how relevant a gene-set is. For both of these...

  • Evaluation of Allelic Expression of Imprinted Genes in Adult Human Blood. Frost, Jennifer M.; Monk, Dave; Stojilkovic-Mikic, Taita; Woodfine, Kathryn; Chitty, Lyn S.; Murrell, Adele; Stanier, Philip; Moore, Gudrun E. // PLoS ONE;2010, Vol. 5 Issue 10, p1 

    Background: Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as...

  • MicroRNA Expression Aberration as Potential Peripheral Blood Biomarkers for Schizophrenia. Lai, Chi-Yu; Yu, Sung-Liang; Hsieh, Ming H.; Chen, Chun-Houh; Chen, Hsuan-Yu; Wen, Chun-Chiang; Huang, Yung-Hsiang; Hsiao, Po-Chang; Hsiao, Chuhsing Kate; Liu, Chih-Min; Yang, Pan-Chyr; Hwu, Hai-Gwo; Chen, Wei J. // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Since brain tissue is not readily accessible, a new focus in search of biomarkers for schizophrenia is blood-based expression profiling of non-protein coding genes such as microRNAs (miRNAs), which regulate gene expression by inhibiting the translation of messenger RNAs. This study aimed to...

  • Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect. Faner, Rosa; Gonzalez, Nuria; Cruz, Tamara; Kalko, Susana Graciela; Agustí, Alvar // PLoS ONE;May2014, Vol. 9 Issue 5, p1 

    Background: Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested...

  • High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. Rui Liao; Jian Sun; Han Wu; Yong Yi; Wang, Jia-Xing; He, Hong-Wei; Cai, Xiao-Yan; Zhou, Jian; Cheng, Yun-Feng; Fan, Jia; Qiu, Shuang-Jian // Journal of Experimental & Clinical Cancer Research (17569966);2013, Vol. 32 Issue 1, p1 

    Background: Hepatocellular carcinoma (HCC) is a typical malignancy in a background of chronic inflammation. Th17 cells (a major source of IL-17) constitute crucial components of infiltrating inflammatory/immune cells in HCC and can amplify inflammatory response via binding to interleukin-17...

  • Diagnostic utility of glypican-3 for hepatocellular carcinoma on liver needle biopsy. Feng Hua Wang; Yuk Ching Yip; Meng Zhang; Heong Ting Vong; Kin Iong Chan; Kit Cheng Wai; Jian Ming Wen // Journal of Clinical Pathology;Jul2010, Vol. 63 Issue 7, p6 

    Aims Glypican 3 (GPC3) is a heparan sulphate proteoglycan that shows elevated levels in the serum of patients with hepatocellular carcinoma (HCC), but not in healthy blood donors or patients with benign liver disease. This study explores the value of GPC3 expression for diagnosis of HCC by...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics