Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

Pallasch, Christian P.; Struss, A.-K.; Munnia, Angela; König, J.; Steudel, Wolf-Ingo; Fischer, Ulrike; Meese, Eckart

doi:10.1002/ijc.20929

Cited by 65 publications

(47 citation statements)

References 27 publications

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“…PHF20 has been identified as an immunologically recognized protein that may represent a novel candidate for cancer-specific immunotherapy [1][2][3]. Patients with malignant cancer may develop an autoimmune response as a consequence of generation of autoantibodies against various antigens, the clinical significance of which is not clear [35].…”

Section: Discussionmentioning

confidence: 99%

“…PHF20 shows the most frequent antibody response in glioma patients [2], and auto-antibodies against PHF20 significantly correlated with prolonged survival in patients with glioblastoma [3]. Paradoxically, lower survival was observed in non-small-cell lung carcinoma (NSCLC) patients with PHF20 [4].…”

Section: Introductionmentioning

confidence: 99%

“…PKB activation occurs when PtdIns [3,4,5]P3 (a product of PI3K) binds to the pleckstrin homology (PH) domain of PKB. Phosphorylation of two amino acids (Thr308 and Ser473) is then required for full PKB activation [14].…”

Section: Introductionmentioning

confidence: 99%

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PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

Park

et al. 2013

Cellular Signalling

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Publisher rights This is the author's version of a work that was accepted for publication in Cellular Signalling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cellular Signalling, VOL25, ISSUE1, 01/2013General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Running Head: Regulation of PHF20 by PKB Keywords : PHF20, Glioblastoma, PKB, p53, protein phosphorylation A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract PHD finger protein 20 (PHF20) is a transcription factor, which was originally identified in glioma patients. PHF20 appears to be a novel antigen in glioma, and has also termed gliomaexpressed antigen 2. PHF20 is thought to contribute to the development of cancers, including glioblastoma, lung cancer, colon cancer and ovarian cancer. However, little is known about the function of PHF20 in various cancers. Here we report that PHF20 contains two consensus sites for protein kinase B (PKB) phosphorylation (RxRxxS/T). PKB can directly phosphorylate PHF20 on Ser291 in vitro and in vivo. It has been shown that PKB participates in the tumor suppressor p53 regulated gene expression program and has a direct effect on p21 regulation after DNA damage. UV induced DNA damage result in accumulation of p53 and PKB activation. Interestingly, PKB-mediated PHF20 phosphorylation led to an inhibition of p53 induction following UV treatment, leading to the reduction of p21 transcriptional activity.Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

Park

et al. 2013

Cellular Signalling

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“…Les anticorps anti-NY-ESO-1 ont été ensuite détectés avec une fréquence variant entre 20 et 50 % dans d'autres cancers comme le cancer bronchique non à petites cellules [8], le cancer de la prostate [9], le cancer médullaire de la thyroïde [10] et le mélanome [11]. Par la suite, d'autres AAT ont été étudiés, comme la protéine CAGE-1 (cancer/testis antigen gene) dans le cancer du poumon [12], NY-BR-1, ING1 et hMena dans le cancer du sein [13,14], GLEA1 (glioma expressed antigen 1), GLEA2 et PHF3 (PHD finger protein 3) dans le glioblastome [15]. Il est intéressant de mentionner que certains de ces autoanticorps présentent un intérêt comme marqueurs diagnostiques précoces ou marqueurs prédictifs d'une réponse thérapeutique.…”

Section: Analyse Sérologique Des Banques D'expression D'adncunclassified

“…Il est intéressant de mentionner que certains de ces autoanticorps présentent un intérêt comme marqueurs diagnostiques précoces ou marqueurs prédictifs d'une réponse thérapeutique. C'est le cas des anticorps anti-NY-ESO-1, présents dès les formes précoces de cancer du poumon [8], ou pour les anticorps anti-GLEA2 et anti-PHF3, associés à un pronostic favorable chez les patients atteints d'un glioblastome [15]. Malgré ces résultats très prometteurs, le SEREX pré-sente plusieurs inconvénients, inhérents pour la plupart à la technique.…”

Section: Analyse Sérologique Des Banques D'expression D'adncunclassified

Étude de la réaction immunitaire humorale aux cancers par des approches protéomiques

2008

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IgM and IgA augmented autoantibody signatures improve early‐stage detection of colorectal cancer prior to nodal and distant spread

et al. 2021

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Objectives Tumor‐associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa‐associated IgA can aid IgG AAbs in the detection of early‐stage colorectal cancer (CRC). Methods We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex‐ and age‐matched non‐cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and univariate and multivariate Cox regression analyses were conducted. Results We identified a panel of 16 multi‐isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850–0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884–0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440–0.601) balanced across all CRC stages. Kaplan–Meier analysis revealed that se33‐1 (ZNF638) IgG AAbs were associated with reduced 5‐year overall survival (log‐rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5‐year overall survival (log‐rank test, P = 0.024). Conclusion IgM AAbs are associated with early‐stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.

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Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival

Cited by 65 publications

References 27 publications

PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

Étude de la réaction immunitaire humorale aux cancers par des approches protéomiques

IgM and IgA augmented autoantibody signatures improve early‐stage detection of colorectal cancer prior to nodal and distant spread

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