Discovery and Preclinical Validation of Salivary Transcriptomic and Proteomic Biomarkers for the Non-Invasive Detection of Breast Cancer

Zhang, Lei; Xiao, Hua; Karlan, Scott; Zhou, Hui; Gross, Jenny; Elashoff, David; Akin, David; Yan, Xinmin; Chia, David; Karlan, Beth Y.; Wong, David T.

doi:10.1371/journal.pone.0015573

Cited by 232 publications

(181 citation statements)

References 55 publications

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“…Currently, the growing research field of circulating biomarkers present in the body fluids or 'liquid biopsy,' promises to revolutionize the undetected malignant cells or their molecular biomarkers (2,(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

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Proteomic profile of saliva and plasma from women with impalpable breast lesions

et al. 2016

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Abstract. The present study evaluated the proteomic profile of saliva and plasma from women with impalpable breast lesions using nano-liquid chromatography-quadrupole-time-of-flight (nLC-Q-TOF) technology. Plasma and saliva from patients with fibroadenoma (n=10), infiltrating ductal carcinoma (n=10) and healthy control groups (n=8) were assessed by combinations of inter/intra-group analyses, revealing significant quantitative and qualitative differences. The major differentially-expressed proteins in the saliva of patients compared with the controls were α2-macroglobulin and ceruloplasmin, but the proteins that met the minimum fold-change and P-value cut-offs were leukocyte elastase inhibitor and α-enolase, and deleted in malignant brain tumors 1. Concerning plasma, α-2-macroglobulin and ceruplasmin were upregulated, while other proteins such as haptoglobin, hemopexin and vitamin D-binding protein were downregulated compared with the control. The changes in immune, molecular transport and signaling pathways were the most representative in the proteomic profile of the saliva and plasma. This is the first study to describe the proteome of saliva and plasma from the same women with impalpable breast lesions.

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Section: Introductionmentioning

confidence: 99%

“…More recently, saliva has become a new alternative source for biomarkers that can reveal local and systemic diseases (7)(8)(9). Saliva is a liquid less complex than blood, but it remains able to contain the same proteins and represent the pathological condition of the individual (6,10).…”

Section: Introductionmentioning

confidence: 99%

Proteomic profile of saliva and plasma from women with impalpable breast lesions

et al. 2016

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“…The samples were all collected, processed, and stored in a similar fashion. Unstimulated saliva samples were consistently collected, stabilized, and preserved as previously described (31). The sample supernatants were kept at Ϫ80°C prior to assay.…”

Section: Methodsmentioning

confidence: 99%

“…Human saliva is an attractive early detection biofluid (26,27,28) because its collection is noninvasive, and it contains a large array of proteins, many of which have been shown to be informative for the detection of oral (29,30) and systemic diseases (31,32,33). Systemic diseases, like lung cancer, may affect salivary glands directly or indirectly, and may influence the quantity of saliva that is produced, as well as the composition (26,27,34).…”

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confidence: 99%

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

Xiao¹,

Zhang²,

Zhou³

et al. 2012

Molecular & Cellular Proteomics

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Lung cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. Early detection represents one of the most promising approaches to reduce the growing lung cancer burden. Human saliva is an attractive diagnostic fluid because its collection is less invasive than that of tissue or blood. Profiling of proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of oral or systematic diseases, which may be used extensively in future medical diagnostics. There were 72 subjects enrolled in this study for saliva sample collection according to the approved protocol. Two-dimensional difference gel electrophoresis combined with MS was the platform for salivary proteome separation, quantification, and identification from two pooled samples. Candidate proteomic biomarkers were verified and prevalidated by using immunoassay methods. There were 16 candidate protein biomarkers discovered by two-dimensional difference gel electrophoresis and MS. Three proteins were further verified in the discovery sample set, prevalidation sample set, and lung cancer cell lines. The discriminatory power of these candidate biomarkers in lung cancer patients and healthy control subjects can reach 88.5% sensitivity and 92.3% specificity with AUC ‫؍‬ 0.90. This preliminary data report demonstrates that proteomic biomarkers are present in human saliva when people develop lung cancer. The discriminatory power of these candidate biomarkers indicate that a simple saliva test might be established for lung cancer clinical screening and detection. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.012112, 1-12, 2012.Lung cancer has long been a significant worldwide public health issue. In the United States, lung cancer is the most common cause of cancer-related death in men and women. According to the American Cancer Society, the major type of lung cancer is non-small-cell lung cancer (NSCLC) 1 , which comprises ϳ85% of lung cancers (1, 2). Small cell lung cancer (SCLC) is another type of lung cancer, which represents about 15% of cases (3). Cigarette smoking causes lung cancer, which is by far the major risk factor (4, 5, 6). Lung cancer has a high mortality rate among malignancies, in part because symptoms are frequently absent until disease is already metastatic and is, therefore, incurable (7,8,9). Early detection represents a very promising approach to reduce lung cancer incidence and mortality. However, conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are either expensive and occasionally miss tumors or invasive cancer (10,11,12,13). Computed tomography has been wildly used for lung cancer early screening, although it often produces a high rate of false positives (7,14,15). Better diagnostic methods are urgently needed to improve the detection of lung cancer.Tissue and blood have been extensively used in attempts to detect lung cancer earlier (1,16,17,18). Sputum has also been used to predict lung cancer by detecting its aberra...

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“…Cell-free saliva has been found to contain over a thousand proteins involved in a wide range of biologic functions, 3 as well as messenger RNA (mRNA) and micro RNA (miRNA) transcripts [4][5][6] and metabolites. 7,8 Saliva proteins, mRNA, miRNA, and metabolites are proving useful for diagnostic purposes, as their increased and decreased occurrence in saliva is being found to reflect oral as well as systemic disease.…”

Section: Saliva: the Biofluidmentioning

confidence: 99%

Salivary Diagnostics

Wong

2012

Operative Dentistry

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The past 10 years have witnessed significant advances in the science and technology of salivary diagnostics. The integration of salivary diagnostics into the clinical practice of dentistry is on the horizon to enable chair-side detection of oral and systemic disorders in the dental office. SUMMARYSaliva is a noninvasive and accessible biofluid that permits early detection of oral and systemic diseases. Recent scientific and technologic advances have uncovered specific salivary biomarkers for a number of clinical conditions, including cancers, autoimmune diseases, and cardiovascular disorders. The availability of highly sensitive and highthroughput assays such as microarray, mass spectrometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and nano-scale sensors that can measure proteins and nucleic acids are poising saliva as an emerging biofluid for translational and clinical applications. This paper will discuss development of salivary biomarkers for the detection of oral and systemic diseases and the translational application of these markers for clinical applications.

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Discovery and Preclinical Validation of Salivary Transcriptomic and Proteomic Biomarkers for the Non-Invasive Detection of Breast Cancer

Cited by 232 publications

References 55 publications

Proteomic profile of saliva and plasma from women with impalpable breast lesions

Proteomic profile of saliva and plasma from women with impalpable breast lesions

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

Salivary Diagnostics

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