Peptides from the Variable Region of Specific Antibodies Are Shared among Lung Cancer Patients

Costa, Dominique de; Broodman, Ingrid; Calame, Wim; Stingl, Christoph; Dekker, Lennard J. M.; Vernhout, René M.; Koning, Harry J. de; Hoogsteden, Henk C.; Klaveren, Rob J. van; Luider, Theo M.; VanDuijn, Martijn M.

doi:10.1371/journal.pone.0096029

Cited by 14 publications

(20 citation statements)

References 30 publications

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“…Overall, 1,380 publications that did not meet the inclusion criteria were excluded based on the titles and abstracts. Among the remaining 77 full-text articles, 7 were excluded because no outcomes of interest were reported [ 20 – 26 ], 3 were excluded because the participants were not evaluated for serum autoantibodies [ 27 – 29 ], 2 were excluded because it was neither in English or Chinese [ 30 , 31 ]. One article was excluded because the autoantibody was not performed in the serum [ 32 ], and another one was excluded because of duplicate data [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

et al. 2017

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ObjectiveWe performed a comprehensive review and meta-analysis to evaluate the diagnostic values of serum single and multiplex tumor-associated autoantibodies (TAAbs) in patients with lung cancer (LC).MethodsWe searched the MEDLINE and EMBASE databases for relevant studies investigating serum TAAbs for the diagnosis of LC. The primary outcomes included sensitivity, specificity and accuracy of the test.ResultsThe systematic review and meta-analysis included 31 articles with single autoantibody and 39 with multiplex autoantibodies. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method. For the diagnosis of patients with all stages and early-stage LC, different single or combinations of TAAbs demonstrated different diagnostic values. Although individual TAAbs showed low diagnostic sensitivity, the combination of multiplex autoantibodies offered relatively high sensitivity. For the meta-analysis of a same panel of autoantibodies in patients at all stages of LC, the pooled results of the panel of 6 TAAbs (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2) were: sensitivity 38% (95% CI 0.35–0.40), specificity 89% (95% CI 0.86–0.91), diagnostic accuracy 65.9% (range 62.5–81.8%), AUC 0.52 (0.48–0.57), while the summary estimates of 7 TAAbs (p53, CAGE, NY-ESO-1, GBU4-5, SOX2, MAGE A4 and Hu-D) were: sensitivity 47% (95% CI 0.34–0.60), specificity 90% (95% CI 0.89–0.92), diagnostic accuracy 78.4% (range 67.5–88.8%), AUC 0.90 (0.87–0.93). For the meta-analysis of the same panel of autoantibodies in patients at early-stage of LC, the sensitivities of both panels of 7 TAAbs and 6 TAAbs were 40% and 29.7%, while their specificities were 91% and 87%, respectively.ConclusionsSerum single or combinations of multiplex autoantibodies can be used as a tool for the diagnosis of LC patients at all stages or early-stage, but the combination of multiplex autoantibodies shows a higher detection capacity; the diagnostic value of the panel of 7 TAAbs is higher than the panel of 6 TAAbs, which may be used as potential biomarkers for the early detection of LC.

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Section: Resultsmentioning

confidence: 99%

Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

et al. 2017

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“…Hints that support such assumptions come from other studies that show the diseasespecific accumulation of distinct complementarity determining region peptides (CDR peptides) of the highly variable region of AAbs in glaucoma and other diseases. [43][44][45] From these findings, it seems likely that not only alterations of the antigen but also of the AAbs themselves can lead to the onset of autoimmune processes. This raises an interesting question for future studies that aim to analyse whether alterations of either antibody or target protein can influence the binding properties.…”

Section: Discussionmentioning

confidence: 99%

“…A hypothesis that needs further validation by subsequent experiments is that not only quantitative but also qualitative differences between natural and disease‐related AAbs may play a role. Hints that support such assumptions come from other studies that show the disease‐specific accumulation of distinct complementarity determining region peptides (CDR peptides) of the highly variable region of AAbs in glaucoma and other diseases . From these findings, it seems likely that not only alterations of the antigen but also of the AAbs themselves can lead to the onset of autoimmune processes.…”

Section: Discussionmentioning

confidence: 99%

Autoantigens in the trabecular meshwork and glaucoma‐specific alterations in the natural autoantibody repertoire

et al. 2020

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Objectives Primary open‐angle glaucoma (POAG) is a neurodegenerative disorder leading to a gradual vision loss caused by progressive damage to the optic nerve. Immunological processes are proposed to be involved in POAG pathogenesis. Altered serological autoantibody levels have been frequently reported, but complete analyses of the natural autoantibodies with respect to disease‐related alterations are scarce. Here, we provide an explorative analysis of pathways and biological processes that may involve naturally immunogenic proteins and highlight POAG‐specific alterations. Methods Mass spectrometry‐based antibody‐mediated identification of autoantigens (MS‐AMIDA) was carried out in healthy and glaucomatous trabecular meshwork (TM) cell lines, using antibody pools purified from serum samples of 30 POAG patients and 30 non‐glaucomatous subjects. Selected antigens were validated by protein microarray (n = 120). Bioinformatic assessment of identified autoantigens, including Gene Ontology (GO) enrichment analysis and protein–protein interaction networks, was applied. Results Overall, we identified 106 potential autoantigens [false discovery rate (FDR) < 0.01], from which we considered 66 as physiological targets of natural autoantibodies. Twenty‐one autoantigens appeared to be related to POAG. Bioinformatic analysis revealed that the platelet‐derived growth factor receptor beta (PDGFRB) pathway involved in TM fibrosis was particularly rich in POAG‐related antigens. Antibodies to threonine‐tRNA ligase (TARS), component 1 Q subcomponent‐binding protein (C1QBP) and paraneoplastic antigen Ma2 (PNMA2) showed significantly (P < 0.05) higher levels in POAG patients as validated by protein microarray. Conclusion This study provides new insights into autoimmunity in health and glaucoma. Bioinformatic analysis of POAG‐related autoantigens showed a strong association with the PDGFRB pathway and also increased levels of PNMA2, TARS, and C1QBP autoantibodies in the serum of POAG patients as potential glaucoma biomarkers.

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“…In addition, Hong et al also found that 131I-anti-ProGRP(31–98)scFv, which can bind to progastrin-releasing peptide(31–98) (ProGRP(31–98)), had a high level of selective uptake by tumor tissues, but a low level in normal tissues, indicating that it could be used for SCLC radioimmunoimaging [ 62 ]. Impressively, de Costa et al first found that peptides generated from variable antibodies were shared among lung cancer patients but not a control group [ 25 ], suggesting that these peptides could be novel biomarkers for screening lung cancer. Evidence also showed that the peptide HCBP-1 has exhibited specific binding to lung cancer stem cells, suggesting that this peptide may be used to identify lung cancer stem cells and as a drug carrier to lung cancer stem cells [ 26 ].…”

Section: Peptides and Lung Cancermentioning

confidence: 99%

Peptide-Based Treatment: A Promising Cancer Therapy

Xiao

Jie

et al. 2015

Journal of Immunology Research

133

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Many new therapies are currently being used to treat cancer. Among these new methods, chemotherapy based on peptides has been of great interest due to the unique advantages of peptides, such as a low molecular weight, the ability to specifically target tumor cells, and low toxicity in normal tissues. In treating cancer, peptide-based chemotherapy can be mainly divided into three types, peptide-alone therapy, peptide vaccines, and peptide-conjugated nanomaterials. Peptide-alone therapy may specifically enhance the immune system's response to kill tumor cells. Peptide-based vaccines have been used in advanced cancers to improve patients' overall survival. Additionally, the combination of peptides with nanomaterials expands the therapeutic ability of peptides to treat cancer by enhancing drug delivery and sensitivity. In this review, we mainly focus on the new advances in the application of peptides in treating cancer in recent years, including diagnosis, treatment, and prognosis.

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Peptides from the Variable Region of Specific Antibodies Are Shared among Lung Cancer Patients

Cited by 14 publications

References 30 publications

Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

Autoantigens in the trabecular meshwork and glaucoma‐specific alterations in the natural autoantibody repertoire

Peptide-Based Treatment: A Promising Cancer Therapy

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