Infrequent Presence of Anti-c-Myc Antibodies and Absence of c-Myc Oncoprotein in Sera from Lung Cancer Patients

Yamamoto, Akira; Shimizu, Eiji; Takeuchi, Eiji; Doi, Hiroyuki; Bando, Hiroyasu; Ogura, Takeshi; Sone, Saburo

doi:10.1159/000011953

Cited by 32 publications

(18 citation statements)

References 13 publications

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“…This feature is one of the innovative notions in this study. Previous observations show that antibodies to any individual antigen such as p53 [8,30], c-myc [30,33], p62 [30] or NY-Eso-1 [34] do not reach levels of sensitivity which could become routinely useful in diagnosis. Recent studies indicate that combinations of multiple antigen-antibody systems may acquire higher sensitivity for diagnosis of cancer [30,32].…”

Section: Discussionmentioning

confidence: 99%

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Zhang

Megliorino

Peng

et al. 2007

Journal of Hepatology

113

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Background/Aims-Previous studies have demonstrated that during transition from chronic liver disease to hepatocellular carcinoma (HCC), autoantibodies can appear which are not detected in the prior pre-malignant conditions. These antibody responses may be stimulated by cellular proteins involved in carcinogenesis. This study determines the prevalence of antibodies to a selected panel of eight tumor-associated antigens (TAAs) in sera from patients with chronic hepatitis, liver cirrhosis and HCC, and considers the possibility and usefulness of antibodies to such a panel of TAAs in differentiating between these conditions. The panel of eight TAAs includes Imp1, p62, Koc, p53, cmyc, cyclin B1, survivin and p16 full-length recombinant proteins.Methods-Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against eight selected TAAs in 30 sera from chronic hepatitis, 30 from liver cirrhosis, and 142 from HCC. Positive results were also confirmed by slot blot, Western blotting and immunoprecipitation assay.Results-Antibody frequency to any individual TAA in HCC varied from 9.9%-21.8%. With the successive addition of TAAs to a final total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a frequency of 59.8% with whole cohort of HCC patients. This was significantly higher than the frequency of antibodies in chronic hepatitis (20%), liver cirrhosis (30%) and normal individuals (12.2%).Conclusions-This study demonstrates that malignant transition to HCC is associated with increased autoantibody responses to certain cellular proteins which might have a role in tumorigenesis, and shows that a mini-array of eight TAAs enhanced antibody detection for diagnosis of HCC. More studies in patients with HCC and precursor conditions such as chronic hepatitis, alcoholic hepatitis and liver cirrhosis using enlarged TAA mini-array panels might further improve the sensitivity and specificity of this mode of cancer immunodiagnosis. Its additional usefulness might be in the early detection of cancer in some patients with predisposing conditions.

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Section: Discussionmentioning

confidence: 99%

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Zhang

Megliorino

Peng

et al. 2007

Journal of Hepatology

113

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“…Detection of anti-p53 autoantibodies may serve not only to diagnose early-stage malignancy but also to monitor tumor progression and recurrence (2). However, little work about autoantibodies against other proteins has been described (3,4). This may be attributed to conventional methods for detecting antibodies: enzyme immunoassay for predefined specific proteins, such as oncogene products and glycoproteins.…”

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confidence: 99%

Proteomics-Based Approach Identifying Autoantibody against Peroxiredoxin VI as a Novel Serum Marker in Esophageal Squamous Cell Carcinoma

Fujita¹,

Nakanishi

Hiramatsu³

et al. 2006

Clinical Cancer Research

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Purpose: Detection of novel tumor-related antigens and autoantibodies will aid in diagnosis of early-stage cancer and in development of more effective immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomicsbased approach. Experimental Design: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Results: Sera from patients with ESCC yielded multiple spots, one of which was identified as peroxiredoxin (Prx) VI by MALDI-TOF/TOF MS. Western blot analysis against recombinant Prx VI showed reactivity in sera from 15 of 30 (50%) patients with ESCC and 2 of 30 (6.6%) healthy individuals. Autoantibody against PrxVI was found in sera from 1of 30 (3.3%) patients with other types of cancer (colon cancer). Conclusion: We have identified for the first time an autoantibody against PrxVI in ESCC patients. The proteomic approach implemented here offers a powerful tool for identifying novel serum markers that may display clinical usefulness against cancer.

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“…They include differentiation antigens and other proteins that are overexpressed in tumors (5). The oncogenic proteins L-Myc and C-Myc have been found to elicit autoantibodies in a small percentage of patients (1,6). There is some evidence that occurrence of autoantibodies in lung cancer is of prognostic relevance (7)(8)(9).…”

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confidence: 99%

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

Brichory

Misek

Yim

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

284

204

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The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and͞or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and͞or II in sera from patients with lung cancer.

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Infrequent Presence of Anti-c-Myc Antibodies and Absence of c-Myc Oncoprotein in Sera from Lung Cancer Patients

Cited by 32 publications

References 13 publications

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Antibody detection using tumor-associated antigen mini-array in immunodiagnosing human hepatocellular carcinoma

Proteomics-Based Approach Identifying Autoantibody against Peroxiredoxin VI as a Novel Serum Marker in Esophageal Squamous Cell Carcinoma

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

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