Dataset Information

Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer.

ABSTRACT: The majority of non-small-cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here, we utilize a novel approach based on whole genome-derived tiled peptide arrays to identify epitopes associated with autoantibody reactivity in NSCLC as a potential means for early detection. Arrays consisted of 2,781,902 tiled peptides representing 20,193 proteins encoded in the human genome. Analysis of 86 prediagnostic samples and 86 matched normal controls from a high-risk cohort revealed 48 proteins with three or more reactive epitopes in NSCLC samples relative to controls. Independent mass spectrometry analysis identified 40 of the 48 proteins in prediagnostic sera from NSCLC samples, of which, 21 occurred in the immunoglobulin-bound fraction. In addition, 63 and 34 proteins encompassed three or more epitopes that were distinct for squamous cell lung cancer and lung adenocarcinoma, respectively. Collectively, these data show that tiled peptide arrays provide a means to delineate epitopes encoded across the genome that trigger an autoantibody response associated with tumor development. SIGNIFICANCE: This study provides a modality for early diagnosis of NSCLC for precision oncology that can be applied to other cancer types.

SUBMITTER: Yan Y

PROVIDER: S-EPMC6445725 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer.

Yan Yuanqing Y Sun Nan N Wang Hong H Kobayashi Makoto M Ladd Jon J JJ Long James P JP Lo Ken C KC Patel Jigar J Sullivan Eric E Albert Thomas T Goodman Gary E GE Do Kim-Anh KA Hanash Samir M SM

Cancer research 20190205 7

The majority of non-small-cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here, we utilize a novel approach based on whole genome-derived tiled peptide arrays to identify epitopes associated with autoantibod ...[more]

PMID: 30723114

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Project description:BackgroundLipopolysaccharide (LPS) is recognized as the most potent microbial mediator presaging the threat of invasion of Gram-negative bacteria that implicated in the pathogenesis of sepsis and septic shock. This study was designed to examine the microRNA (miRNA) expression in whole blood from mice injected with intraperitoneal LPS.MethodsC57BL/6 mice received intraperitoneal injections of varying concentrations (range, 10-1000 μg) of LPS from different bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Salmonella enterica, and Serratia marcescens and were killed 2, 6, 24, and 72 h after LPS injection. Whole blood samples were obtained and tissues, including lung, brain, liver, and spleen, were harvested for miRNA expression analysis using an miRNA array (Phalanx miRNA OneArray® 1.0). Upregulated expression of miRNA targets in the whole blood of C57BL/6 and Tlr4(-/-) mice injected with LPS was quantified using real-time RT-PCR and compared with that in the whole blood of C57BL/6 mice injected with lipoteichoic acid (LTA) from Staphylococcus aureus.ResultsFollowing LPS injection, a significant increase of 15 miRNAs was observed in the whole blood. Among them, only 3 miRNAs showed up-regulated expression in the lung, but no miRNAs showed a high expression level in the other examined tissues. Upregulated expression of the miRNA targets (let-7d, miR-15b, miR-16, miR-25, miR-92a, miR-103, miR-107 and miR-451) following LPS injection on real-time RT-PCR was dose- and time-dependent. miRNA induction occurred after 2 h and persisted for at least 6 h. Exposure to LPS from different bacteria did not induce significantly different expression of these miRNA targets. Additionally, significantly lower expression levels of let-7d, miR-25, miR-92a, miR-103, and miR-107 were observed in whole blood of Tlr4(-/-) mice. In contrast, LTA exposure induced moderate expression of miR-451 but not of the other 7 miRNA targets.ConclusionsWe identified a specific whole blood-derived miRNA signature in mice exposed to LPS, but not to LTA, from different gram-negative bacteria. These whole blood-derived miRNAs are promising as biomarkers for LPS exposure.

Dataset Information

Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer.

Publications

Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer.

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