Serum anti-p53 antibodies in patients with lung cancer.

Mack, Ulrich; Ukena, D.; Montenarh, Mathias; Sybrecht, Gerhard W.

doi:10.3892/or.7.3.669

Cited by 31 publications

(33 citation statements)

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“…Most notably, autoantibodies directed against p53 correlate with poor prognosis. [19][20][21] Likewise, autoantibodies associated with paraneoplastic syndromes have been correlated with poor prognosis and are thought to lead to fatal neurologic disorders. 22,23 Autoantibodies correlated with prolonged survival of tumor patients are rare and to the best of our knowledge of low specificity.…”

Section: Discussionmentioning

confidence: 99%

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

Pallasch

Struss

Munnia

et al. 2005

Intl Journal of Cancer

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Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma‐expressed antigens including GLEA1, GLEA2 and PHD‐finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1‐autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma‐associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma. © 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

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

Pallasch

Struss

Munnia

et al. 2005

Intl Journal of Cancer

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“…This idea largely stems from the popular notion that although a cancer is still asymptomatic and in its early stages, autoantibodies produced in response to cancerspecific antigens may be detectable due to signal amplification from the humoral immune response. To date, numerous autoantibody targets have been evaluated for their value in early detection of lung cancer or for prognostication (13,16,19,22,27,(34)(35)(36)(37)(38)(39). Despite the promise these studies have shown in this direction, little has been done outside the initial discovery efforts to validate these findings and to translate these promising antibodies into a clinically usable test.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant proteins were obtained for each of the candidate autoantibodies identified in the proteomic discovery efforts having value for NSCLC detection (see Table 2) as well as for a second group of autoantibodies with documented value for our purpose, including NY-ESO (13-15), p53 (13,(16)(17)(18)(19)(20)(21), peroxiredoxin (22,23), triosephosphate isomerase (23), recoverin (24), 3-oxoacid CoA transferase (23), survivin (also known as BIRC5; ref. 25), c-Myc (13,26), Annexin II (27), and ubiquillin (28).…”

Section: Serum Test Developmentmentioning

confidence: 99%

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Farlow

Patel

Basu

et al. 2010

Clinical Cancer Research

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Purpose: Non-small cell lung cancer (NSCLC) has an overall 5-year survival of <15%; however, the 5-year survival for stage I disease is over 50%. Unfortunately, 75% of NSCLC is diagnosed at an advanced stage not amenable to surgery. A convenient serum assay capable of unambiguously identifying patients with NSCLC may provide an ideal diagnostic measure to complement computed tomography-based screening protocols.Experimental Design: Standard immunoproteomic method was used to assess differences in circulating autoantibodies among lung adenocarcinoma patients relative to cancer-free controls. Candidate autoantibodies identified by these discovery phase studies were translated into Luminex-based "direct-capture" immunobead assays along with 10 autoantigens with previously reported diagnostic value. These assays were then used to evaluate a second patient cohort composed of four discrete populations, including: 117 NSCLC (81 T 1-2 N 0 M 0 and 36 T 1-2 N 1-2 M 0 ), 30 chronic obstructive pulmonary disorder (COPD)/ asthma, 13 nonmalignant lung nodule, and 31 "normal" controls. Multivariate statistical methods were then used to identify the optimal combination of biomarkers for classifying patient disease status and develop a convenient algorithm for this purpose.Results: Our immunoproteomic-based biomarker discovery efforts yielded 16 autoantibodies differentially expressed in NSCLC versus control serum. Thirteen of the 25 analytes tested showed statistical significance (Mann-Whitney P < 0.05 and a receiver operator characteristic "area under the curve" over 0.65) when evaluated against a second patient cohort. Multivariate statistical analyses identified a six-biomarker panel with only a 7% misclassification rate.Conclusions: We developed a six-autoantibody algorithm for detecting cases of NSCLC among several high-risk populations. Population-based validation studies are now required to assign the true value of this tool for identifying early-stage NSCLC. Clin Cancer Res; 16(13); 3452-62. ©2010 AACR.Lung cancer remains the leading cause of cancer death nationwide, with ∼160,000 deaths predicted in the United States in 2009 (1). Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers and has a poor overall 5-year survival rate of ∼15% (2-4). This low survival rate is largely attributed to the fact that >75% of patients present with local or distant metastasis at diagnosis, which are associated with a 21% and 3% 5-year survival, respectively (2,3,5). In contrast to these dismal figures, stage I disease is associated with a 50% to 67% 5-year survival but accounts for only 15% of patients (2). This suggests that if patients could be diagnosed at an earlier stage, when a complete surgical resection offers the greatest potential for a cure, the mortality associated with this disease could be reduced.To that end, considerable efforts have been undertaken to produce an effective screening method for early NSCLC. In the 1950s, trials of chest X-rays alone or in combination with sputum analysis were com...

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“…p53 Ab production is associated with TP53 gene mutation in CRC tissue and the consequent accumulation of mutant TP53 protein. The p53 Ab can be found in 13-47% of CRC patients [5,6,7,8,9,10], and its elevation has been reported in a wide variety of solid cancers such as esophageal, gastric, lung, ovarian, and hepatocellular cancers [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Thus, the clinical applicability of the p53 Ab in cancer screening is well established.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Pre- and Postoperative Anti-p53 Antibody Levels in Colorectal Cancer Patients: A Retrospective Study

Abe

Kawai²,

Ishihara³

et al. 2016

Oncology

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Objective: To determine the utility of the post-/preoperative anti-p53 antibody (p53 Ab) ratio as a prognostic factor for colorectal cancer (CRC) recurrence. Methods: A total of 737 nonmetastatic CRC patients who had undergone R0 resection were retrospectively analyzed. p53 Ab levels were measured within 1 month prior to and at least every 3 months after surgery. Post-/preoperative p53 Ab ratios were calculated, and the optimal ratio cutoff values for predicting recurrence were determined using the Kaplan-Meier method and the log-rank test. Results: Preoperative p53 Ab elevation was observed in 194 patients (pre-p53 high). Preoperative p53 Ab levels correlated with TNM stage. Re-elevation of p53 Ab levels occurred on recurrence in the pre-p53 high group, but not in the pre-p53 low group (n = 543). In the pre-p53 high group, patients who experienced tumor recurrence exhibited a slow postoperative reduction of p53 Ab levels, and a post-/preoperative p53 Ab ratio >0.4 at postoperative 3 months predicted relapse-free survival. In other words, a p53 Ab level remaining higher than 40% of the preoperative level was an independent and strong risk factor for recurrence in multivariate analyses. Conclusion: In CRC patients with preoperative p53 Ab elevation, the rate of p53 Ab reduction in the early postsurgical period is a promising prognostic factor for recurrence.

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Serum anti-p53 antibodies in patients with lung cancer.

Cited by 31 publications

References 0 publications

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

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

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Prognostic Value of Pre- and Postoperative Anti-p53 Antibody Levels in Colorectal Cancer Patients: A Retrospective Study

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