Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection

Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary prote...

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Published inScientific reports Vol. 6; no. 1; p. 22165
Main Authors Xiao, Hua, Zhang, Yan, Kim, Yong, Kim, Sung, Kim, Jae Joon, Kim, Kyoung Mee, Yoshizawa, Janice, Fan, Liu-Yin, Cao, Cheng-Xi, Wong, David T. W.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 25.02.2016
Nature Publishing Group
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Online AccessGet full text
ISSN2045-2322
2045-2322
DOI10.1038/srep22165

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Abstract Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation.
AbstractList Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation.
Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation.Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation.
ArticleNumber 22165
Author Kim, Sung
Xiao, Hua
Kim, Yong
Yoshizawa, Janice
Cao, Cheng-Xi
Kim, Jae Joon
Zhang, Yan
Wong, David T. W.
Kim, Kyoung Mee
Fan, Liu-Yin
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  surname: Xiao
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  organization: State Key Laboratory of Microbial Metabolism, Laboratory of Bioseparation and Analytical Biochemistry, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
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  givenname: Yan
  surname: Zhang
  fullname: Zhang, Yan
  organization: School of Pharmacy, Shanghai Jiao Tong University
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  givenname: Yong
  surname: Kim
  fullname: Kim, Yong
  organization: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles
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  givenname: Sung
  surname: Kim
  fullname: Kim, Sung
  organization: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine
– sequence: 5
  givenname: Jae Joon
  surname: Kim
  fullname: Kim, Jae Joon
  organization: Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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  givenname: Janice
  surname: Yoshizawa
  fullname: Yoshizawa, Janice
  organization: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles
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  givenname: Liu-Yin
  surname: Fan
  fullname: Fan, Liu-Yin
  organization: State Key Laboratory of Microbial Metabolism, Laboratory of Bioseparation and Analytical Biochemistry, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
– sequence: 9
  givenname: Cheng-Xi
  surname: Cao
  fullname: Cao, Cheng-Xi
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– sequence: 10
  givenname: David T. W.
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  organization: Dental Research Institute, School of Dentistry, University of California-Los Angeles, Los Angeles
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26911362$$D View this record in MEDLINE/PubMed
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Snippet Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed...
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StartPage 22165
SubjectTerms 631/67/1504/1829
692/53/2421
82/16
82/58
82/81
Adult
Aged
Biomarkers
Biomarkers, Tumor - metabolism
Brain cancer
Brain tumors
Case-Control Studies
Cystatin B - genetics
Cystatin B - metabolism
Cystatins
DMBT1 protein
Enzyme-linked immunosorbent assay
Female
Gastric cancer
Humanities and Social Sciences
Humans
Male
Middle Aged
multidisciplinary
Proteins
Proteome - chemistry
Proteome - genetics
Proteome - metabolism
Proteomics
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Saliva
Saliva - metabolism
Science
Science (multidisciplinary)
Stomach Neoplasms - diagnosis
Stomach Neoplasms - metabolism
Triose-phosphate isomerase
Triose-Phosphate Isomerase - genetics
Triose-Phosphate Isomerase - metabolism
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Title Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection
URI https://link.springer.com/article/10.1038/srep22165
https://www.ncbi.nlm.nih.gov/pubmed/26911362
https://www.proquest.com/docview/1899008637
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https://pubmed.ncbi.nlm.nih.gov/PMC4766442
Volume 6
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