Serum Autoantibody Signature of Ductal Carcinoma <i>In Situ</i> Progression to Invasive Breast Cancer

Mangé, Alain; Lacombe, Jérôme; Bascoul-Mollevi, Caroline; Jarlier, Marta; Lamy, Pierre‐Jean; Rouanet, Philippe; Maudelondé, Thierry; Solassol, Jérôme

doi:10.1158/1078-0432.ccr-11-2527

Cited by 35 publications

(23 citation statements)

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“…Similar findings have been reported by Alain Mange and his colleagues that the serum levels of the antibodies targeting HMGN1 were significantly increased in early-stage invasive breast cancer (IBC) relative to ductal carcinoma in situ (DCIS) [8]. In their work, they firstly examined autoantibody targets in 20 DCIS and 20 IBC patients using protein microarrays and selected a set of five autoantibody targets including HMGN1 could be used to generate an autoantibody signature for the DCIS to IBC transition.…”

Section: Discussionsupporting

confidence: 72%

“…Alain et al [8] demonstrated that the serum levels of the antibodies targeting HMGN1 were significantly increased in invasive breast cancer relative to ductal carcinoma in situ, suggesting it can be a potential predict marker for breast cancer recurrence. By present, there was no achievement indicated the relationship between HMGN1 and lung cancer.…”

Section: Introductionmentioning

confidence: 99%

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High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer

et al. 2015

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The involvement of alarmin high-mobility group nucleosome-binding protein 1 (HMGN1) in non-small cell lung cancer (NSCLC) is unknown. To address the presence of HMGN1 in the serum of different stages of NSCLC patients and healthy controls, we enrolled a consecutive sample of adult serum at diagnosis and correlated it with clinicopathologic outcomes. A total of 100 NSCLC patients and 23 healthy volunteers were enrolled from January 2012 through December 2013. Serum HMGN1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Additionally, HMGN1 levels in 50 NSCLC patients with early-stage disease who received curative pneumonectomy were correlated with survivals. Kaplan-Meier plots were used to analyze the data. The patients with NSCLC were characterized by significantly higher serum levels of HMGN1 (0.4585 ± 0.0640 ng/ml) compared to those in healthy controls (0.3578 ± 0.0304 ng/ml). The serum HMGN1 levels were 0.4027 ± 0.0271 ng/ml, 0.4604 ± 0.0328 ng/ml, 0.5408 ± 0.0459 ng/ml, and 0.4213 ± 0.0341 ng/ml in patients with TNM stages I, II, IV, and IV, respectively (p < 0.001). There were significant differences among four groups (p < 0.001). Additionally, a positive correlation between serum HMGN1 and tumor stage was found in local disease, while serum HMGN1 level in metastatic NSCLC patients was significantly decreased. The Kaplan-Meier plots showed that patients with high serum HMGN1 had a poorer overall survival (OS) after curative pneumonectomy than those with low serum HMGN1 (p = 0.019). Inflammation triggered by alarmins plays a role in NSCLC pathogenesis. HMGN1 can serve as a useful clinical parameter for evaluating disease progression and predicting the outcomes for early-stage patients with NSCLC undergoing pneumonectomy.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer

et al. 2015

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“…Using 120 cancer samples from benign ductal carcinoma in situ or invasive breast cancer, a signature of 5 TAAs (RBP-J kappa, HMGN1, PSRC, CIRBP, and ECHDC1) was able to discriminate patients with an AUC = 0.794. Higher autoantibody titers of RBP-J kappa were found in patients with a higher histotype grade and higher recurrence-free survival for those patients who were positive for the five-antibody signature (Mange et al 2012). Similar results were found in pancreatic cancer (Bracci et al 2012) and glioblastoma multiforme (Pallasch et al 2005), where survival rates were higher in patients with higher levels of autoantibodies to CTDSP1 and NR2E3 and GLEA2 and PHF3 autoantigens, respectively.…”

Section: Identification Of the Minimum Number Of Taas To Be Included supporting

confidence: 73%

Colorectal Cancer Circulating Biomarkers

Barderas¹,

Villar-Vázquez²,

Casal³

2014

Biomarkers in Cancer

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Circulating CRC markers might become useful tools for the massive screening of people since they satisfy a high degree of accuracy, noninvasiveness, reproducibility, and economy. Within circulating biomarkers, we will focus on the detection of autoantibodies in serum from cancer patients and their target tumorassociated antigens (TAAs). Although the sensitivity, specificity, and predictive value of individual TAAs present low scores, the combination of multiple TAAs shows improved values to discriminate between CRC patients and controls. In this review, we outline the methodologies used to identify circulating autoantibodies and their target proteins and discuss the relevance of CRC autoantibodies for diagnosis at, particularly, early stages. An overview of the reported biomarkers is given, showing the large complexity of the autoantibody response in cancer. Different strategies to improve CRC diagnostic tests by combining autoantibodies from different studies will be discussed. Association of autoantibodies to prognosis, recurrence, and the survival of patients will be introduced. We conclude that there is a great potential for the use of autoantibodies as diagnostic CRC biomarkers in the near future. List of Abbreviations Key Facts of Circulating Biomarkers• Tumor-associated antigens (TAAs) are self-proteins altered during tumor formation and progression.• Cancer humoral responses take place against TAAs.• Autoantibodies against TAAs can be used in colorectal cancer patients as circulating biomarkers. • Immunoproteomics provide useful approaches for identifying autoantibodies and their reactive TAA targets.• Circulating autoantibodies provide an effective, reliable, and reproducible tool in cancer patients for diagnosis, prognosis, recurrence, and therapy monitoring.• Targets of circulating autoantibodies might be novel therapeutic targets for intervention. Definitions of Words and TermsBiomarker A biological marker usually a protein or glycoprotein that can be used as an indicator of a biological or pathological state or condition.TAA Tumor-associated antigen which consists of an altered self-protein able to induce an immune response in cancer patients.Autoantibody Immunoglobulin G produced in response to self-proteins altered during tumor formation or progression which can be used as a cancer biomarker.ELISA Enzyme-linked immunosorbent assay which permits to detect the presence of an immune response to a specific TAA in a biological fluid (i.e., serum or plasma) by means of an enzyme immunoassay.SEREX Acronym of serological analysis of recombinant cDNA expression libraries (SEREX) which is a technology based on the detection of tumor-associated antigens within recombinantly expressed tumor cDNA phage libraries by autologous antibodies.SERPA Acronym of serological proteome analysis where proteins from tumoral samples are resolved by 2D gels to identify TAAs by immunostaining with sera from cancer patients and controls. TAAs are then identified in a subsequent step by LC-MS.LC-MS Liquid chromatography ...

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“…Il microarray di proteina è diventato uno degli strumenti più potenti negli studi di proteomica con moltissime possibilità di applicazione, affrontando questioni importanti anche nel campo della proteomica clinica [65]. In effetti, i recenti progressi ottenuti nel campo dell'immunoproteomica con tecnologie ad alta efficienza hanno suggerito, per esempio, che il repertorio di autoanticorpi nei pazienti affetti da cancro possa essere molto diverso rispetto a quello dei soggetti sani, portando all'ipotesi che possano essere identificati degli autoantigeni come marcatori per la diagnosi del cancro, nonché per la sua prognosi [66,67]. Gli autoanticorpi sono stati identificati come i principali attori in diverse malattie immuno-mediate; il danno tissutale e la sua riparazione sono fenomeni di particolare importanza per l'avvio di queste malattie.…”

Section: Microarray DI Proteineunclassified

Panoramica sul microarray

Morozzi

2015

Riv Ital Med Lab

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Ricevuto: 16 marzo 2015 / Accettato: 2 aprile 2015 © Springer-Verlag Italia 2015Riassunto Il microarray, spesso paragonato alla polymerase chain reaction e alle tecniche del DNA ricombinante, è tra le metodiche di biologia molecolare quella di più forte impatto scientifico. Nonostante la tecnica si basi su principi noti della biochimica e della biologia molecolare, come la specificità di legame di sequenze nucleotidiche complementari, a un certo momento del processo evolutivo tecnologico è stato possibile effettuare analisi su grande scala avvalendosi di tecniche miniaturizzate; è stata questa la vera conquista che ha portato gli scienziati a fare un grande "balzo avanti". Esistono varie classi di microarray, tutte di grande interesse sia nel campo della ricerca di base sia nella diagnostica medica. In certi settori della medicina la tecnica è entrata nella diagnostica di routine, mentre in altri rappresenta solo una speranza in attesa di validazione. Esistono problematiche diverse per ciascuna tipologia di microarray; in generale, il disegno sperimentale, l'elaborazione del campione, la normalizzazione dei dati e infine l'analisi e l'interpretazione costituiscono i passaggi fondamentali per produrre risultati con tecnologia microarray. Oggi le tecniche di biologia molecolare permettono l'analisi contemporanea di migliaia di geni, proteine o metaboliti e hanno cambiato la dimensione della ricerca biologica, facendo passare i ricercatori dallo studio dei singoli geni o proteine allo studio sistematico di tutti i geni e proteine. Risulta, quindi, di particolare interesse per la medicina molecolare poter disporre di una visione globale dei processi biologici, aprendo così la strada per migliaia di potenziali applicazioni. Infatti, la disponibilità di tecniche che permettono questo approccio "globale" offre, per esempio, la possibilità di confrontare due diverse B G. Morozzi situazioni biologiche contemporaneamente come, per esempio, lo stato di salute nei confronti della presenza di malattia o un trattamento farmacologico rispetto all'assenza di trattamento ecc., oppure esaminare i processi biologici complessi, le vie metaboliche e le interazioni tra biomolecolecole.Parole chiave Microarray · Applicazioni del microarray · Biologia molecolare · Medicina molecolare Summary The DNA microarray, often compared to the polymerase chain reaction and the recombinant DNA technique, is among the many methods of molecular biology, but the one that has had the strongest scientific impact. Although the technique is based on the known principles of biochemistry and molecular biology, such as the specificity of the binding of complementary nucleotide sequences, but at certain point in the technological evolutionary process, it was possible to perform analysis on a much larger scale while using miniaturized techniques; this was the real achievement that has led scientists to make a great "leap forward". There are various kinds of microarray, all of which are of great interest in both the fields of basic research and in medical diagn...

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Serum Autoantibody Signature of Ductal Carcinoma In Situ Progression to Invasive Breast Cancer

Cited by 35 publications

References 37 publications

High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer

High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer

Colorectal Cancer Circulating Biomarkers

Panoramica sul microarray

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