Identification of tumor-associated antigens by using SEREX in hepatocellular carcinoma

Wang, Kaijuan; Xu, Xueqin; Nie, Yifei; Dai, Liping; Wang, Peng; Zhang, Jianying

doi:10.1016/j.canlet.2009.02.037

Cited by 40 publications

(30 citation statements)

References 24 publications

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“…In microsatellite stable colon cancer, KRT23 expression is highly increased, and this may have a protective function counteracting the proliferation and survival of cells [36]. Another study identified KRT23 as a HCC-associated antigen in patient sera [37]. KRT23 has not yet been described to be expressed in liver or liver disease.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Unravels Cancer-Related Hepatic Molecular Signatures in Steatohepatitis but Not in Steatosis

et al. 2012

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BackgroundPathogenesis and factors for determining progression of alcoholic and non-alcoholic steatosis to steatohepatitis with risk of further progression to liver cirrhosis and cancer are poorly understood. In the present study, we aimed to identify potential molecular signatures for discrimination of steatohepatitis from steatosis.Methodology and ResultsGlobal microarray gene expression analysis was applied to unravel differentially expressed genes between steatohepatitis compared to steatosis and control samples. For functional annotation as well as the identification of disease-relevant biological processes of the differentially expressed genes the gene ontology (GO) database was used. Selected candidate genes (n = 46) were validated in 87 human liver samples from two sample cohorts by quantitative real-time PCR (qRT-PCR). The GO analysis revealed that genes down-regulated in steatohepatitis were mainly involved in metabolic processes. Genes up-regulated in steatohepatitis samples were associated with cancer progression and proliferation. In surgical liver resection samples, 39 genes and in percutaneous liver biopsies, 30 genes were significantly up-regulated in steatohepatitis. Furthermore, immunohistochemical investigation of human liver tissue revealed a significant increase of AKR1B10 protein expression in steatohepatitis.ConclusionsThe development of steatohepatitis is characterized by distinct molecular changes. The most striking examples in this respect were KRT23 and AKR1B10, which we found to be highly differentially expressed in steatohepatitis compared to steatosis and normal liver. We propose that KRT23 and AKR1B10 may serve as future potential biomarkers for steatohepatitis as well as markers for progression to HCC.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Unravels Cancer-Related Hepatic Molecular Signatures in Steatohepatitis but Not in Steatosis

et al. 2012

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“…In contrast, there are no data available, to our knowledge that associates autoantibodies against p53 with patients' clinical characteristics. In patients with colorectal cancer (CRC), there is an increase in the prevalence of anti-p53 autoantibodies in carcinoma in-situ (6%) compared with adenomas (1%), indicating that the level of anti-p53 autoantibody increases with CRC [36] hnRNP L Akada et al [42] HSP70, SOD2, and PRDX6 Shao et al [41] Glucose-regulated protein 78 Nomura et al [39] Ku86 Liu et al [40] CENPF, DDX3, HSPA4, HSPA5, VIM, LMNB1, and p53 Pekáriková et al [21] CRT Chen et al [28] Sui1, RalA Wang et al [43] KRT23, AHSG and FTL Wang et al [44] RalA Looi et al [45] HSP60, HSP70 Li et al [35] DDX3, eEF2, AIF, hnRNP A2, PBP, and TIM Chen et al [46] EIF3SI, LDHA, RFC2, and MCART1 Zhang et al [27] IMP1, IMP2, IMP3, p53, c-myc, cyclin B1, survivin and p16 Akere et al [13] p53 Zhou et al [47] HCC-22-5 Takashima et al [48] HSP70, GAPDH, PRX, Mn-SOD Looi et al [49] p16 Yagihashi et al [25] Survivin Su et al [17] IMP2 Himoto et al [19] IMPs Himoto et al [18] IMPs, p53, c-myc, and survivin Zhang et al [24] c-myc, cyclin B1, IMP1, Koc, p53, IMP2, and survivin Soo Hoo et al [50] p53, IMP2, Koc, CENP-F, p90 Le Naour et al [51] CRT, CK8, NDK-A, and ATP5B Zhang et al [23] IMP2, CENPF Zhang et al [20] IMP2 Raedle et al [52] p53 Covini et al [22] Cyclin B1 Imai et al [53] HCC1 TAAs: Tumor-associated antigens; HCC: Hepatocellular carcinoma; IMP: Insulin-like growth factor mRNA-binding; CENPF: Centromere protein F. 9…”

Section: Association Of the Prevalence Of Autoantibodies With The CLImentioning

confidence: 99%

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Huang

2015

WJH

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Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens (TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.

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“…Techniques such as SEREX [24] T7 phage display [25], two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) [26], amongst others, have been successfully employed for the detection of AAbs raised to TAAs in HCC and in patients with pre-disposing liver disease [27], [28]. However, previous studies have generally been performed using relatively small numbers of TAAs and with inappropriate control groups.…”

Section: Introductionmentioning

confidence: 99%

Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

et al. 2014

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BackgroundIndividuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC.MethodsSerum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA.ResultsVarying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel.ConclusionsThis minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung).

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Identification of tumor-associated antigens by using SEREX in hepatocellular carcinoma

Cited by 40 publications

References 24 publications

Gene Expression Profiling Unravels Cancer-Related Hepatic Molecular Signatures in Steatohepatitis but Not in Steatosis

Gene Expression Profiling Unravels Cancer-Related Hepatic Molecular Signatures in Steatohepatitis but Not in Steatosis

Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma

Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

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