Proteomics‐based identification of α‐enolase as a tumor antigen in non‐small lung cancer

He, Ping; Naka, Tetsuji; Serada, Satoshi; Fujimoto, Minoru; Tanaka, Toshio; Hirano, Shoji; Shima, Yoshihito; Yamadori, Tomoki; Suzuki, Hidekazu; Hirashima, Tomonori; Matsui, Kunihiko; Shiono, Hiroshi; Okumura, Meinoshin; Nishida, Toshiro; Tachibana, Isao; Norioka, Naoko; Norioka, Shigemi; Kawase, Ichiro

doi:10.1111/j.1349-7006.2007.00509.x

Cited by 108 publications

(73 citation statements)

References 27 publications

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“…This approach led to the identification of 31 putative antigenic proteins capable of eliciting a T cell-dependent antibody response, as revealed by IgG production [42,43]. Similar approaches have been used recently to identify relevant antigenic proteins in oncologic, autoimmune, and infectious diseases [44][45][46][47][48][49][50]. To our knowledge, this study is the first to apply an immunoproteomic approach to identify potential antigens in xenotransplanted tissues.…”

Section: Discussionmentioning

confidence: 99%

Immunoproteomic identification of bovine pericardium xenoantigens

et al. 2008

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Bovine pericardium is an important biomaterial with current application in glutaraldehyde-fixed bioprosthetic heart valves and possible future application as an unfixed biological scaffold for tissue engineering. The importance of both humoral and cell-mediated rejection responses toward fixed and unfixed xenogeneic tissues has become increasingly apparent. However, the full scope and specific identities of bovine pericardium proteins that can elicit an immune response remain largely unknown. In this study, an immunoproteomic approach was used to survey bovine pericardium proteins for their ability to elicit a humoral immune response in rabbits. A two-stage protein extraction protocol was used to separate bovine pericardium proteins into water-and lipid-soluble fractions. Two-dimensional gel electrophoresis was performed to separate the proteins from each fraction. Western blots were generated from two-dimensional gels of both bovine pericardium protein fractions. These blots were probed with serum from rabbits immunized with bovine pericardium and a secondary antibody was used to assess for IgG positivity. Western blots were compared to duplicate two-dimensional gels and proteins in matched spots were identified by tandem mass spectrometry. Thirty-one putative protein antigens were identified, eight of which are known to be antigenic from previous studies. All of the putative antigens demonstrated progressive staining intensity with increasing days of post-exposure serum. Identified antigenic proteins represented a variety of functional and structural protein types, and included both cellular and matrix proteins. The results of this study have implications for the use of bovine pericardium as a biomaterial in bioprostheses and tissue engineering applications, as well as xenotransplantation in general.

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Section: Discussionmentioning

confidence: 99%

Immunoproteomic identification of bovine pericardium xenoantigens

et al. 2008

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“…Although many reports show the production of antibodies against autoantigens in cancer patients, [23][24][25] that of these antibodies in healthy individuals remains unclear. This study showed that WT1 IgG Ab was produced in all of the healthy individuals examined.…”

Section: Discussionmentioning

confidence: 99%

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

Oji

Kitamura

Kamino

et al. 2009

Intl Journal of Cancer

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There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzymelinked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean 1 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC. ' UICCKey words: lung cancer; WT1; humoral immune response; tumor marker; prognostic marker Lung cancer is the leading cause of cancer death in the world and nonsmall cell lung cancer (NSCLC) represents nearly 80% of the disease. 1 Because 75% of lung cancer patients are diagnosed at stages of metastatic spread when therapies are rarely curative, 2 early detection of localized lung cancer is the key to improve its clinical outcome.Although chest X-ray is routinely used as a screening tool, its limitation to detect localized lung cancer has been evident because of its insufficient sensitivity. 2 Recently, low-dose spiral computed tomography (CT) has been proposed as an early detection screening tool. However, despite its high sensitivity, specificity of CT in lung cancer detection is poor. 3 Therefore, serum biomarkers with high sensitivity and specificity for diagnosis of lung cancer are needed. However, current serum biomarkers for NSCLC such as carcino embryonic antigens (CEA) and squamous cell carcinoma antigen do not have sufficient sensitivity and specificity required for early detection of NSCLC. 4,5 It is now clear that malignant transformation occurs by changes in cellular gene expression with subsequent clonal proliferation. Altered gene expression in malignant cells may lead to the expression of aberrantly expressed proteins recognized by host immune system. If autoantibodies against these antigens are produced at early stage of NSCLC when quantity of the tumor antigens in the circulation is very small, these...

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“…In addition, enolase 1 was reported to be a hypoxic stress protein and an HSP [8,9]. This molecule has also been considered to be a diagnostic tumor marker [10], and autoantibodies against enolase 1 have been found in numerous autoimmune diseases [11]. A recent work demonstrates the existence of a regulatory circuit between c-myc, MBP-1, and enolase 1 that connects cellular energy metabolism and proliferation [12].…”

Section: Is Enolase 1 a Universal Sensor Regulator Or A Stress Chapmentioning

confidence: 99%

Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins

et al. 2008

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After reading many 2-DE-based articles featuring lists of the differentially expressed proteins, one starts experiencing a disturbing déjà vu. The same proteins seem to predominate regardless of the experiment, tissue or species. To quantify the occurrence of individual differentially expressed proteins in 2-DE experiment reports, we compiled the identities of differentially expressed proteins identified in human, mouse, and rat tissues published in three recent volumes of Proteomics and calculated the appearance of the most predominant proteins in the dataset. The most frequently identified protein is a highly abundant glycolytic enzyme enolase 1, differentially expressed in nearly every third experiment on both human and rodent tissues. Heat-shock protein 27 (HSP27) and heat-shock protein 60 (HSP60) were differentially expressed in about 30 percent of human and rodent samples, respectively. Considering protein families as units, keratins and peroxiredoxins are the most frequently identified molecules, with at least one member of the group being differentially expressed in about 40 percent of all experiments. We suggest that the frequent identification of these proteins must be considered in the interpretation of any 2-DE studies. We consider if these commonly observed changes represent common cellular stress responses or are a reflection of the technical limitations of 2-DE.

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Proteomics‐based identification of α‐enolase as a tumor antigen in non‐small lung cancer

Cited by 108 publications

References 27 publications

Immunoproteomic identification of bovine pericardium xenoantigens

Immunoproteomic identification of bovine pericardium xenoantigens

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins

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