Proteomics Clin Appl. 2009 Jan 1;3(1):116-134.
The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides.
To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released.
A total of 1939 nonredundant salivary proteins were compiled from a total of 19 474 unique peptide sequences identified from whole and ductal salivas; 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma.
The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.
Human papillomavirus in saliva of patients with oral squamous cell carcinoma
Objective: The aim of this study was to evaluate the presence of human papillomavirus (HPV) in saliva rinses of patients with oral squamous cell carcinoma and to analyze the possibility of using saliva as a diagnostic method for screening high-risk patients.
Study design: The saliva sample of 22 patients with oral squamous cell carcinoma and 20 age-sex matched healthy controls were obtained. The presence of HPV 6, 11, 16, 18, 31, and 33 was evaluated by polymerase chain reaction (PCR).
Results: In 40.9% of the patients and in 25% of the controls, the saliva was shown to be positive for HPV. In 27.3% of the patients and in 20% of the controls, the saliva was shown to be positive for HPV16; and none of the controls, except one patient was shown to be positive for HPV 18. Neither patients nor controls were positive for HPV 31 and 33. These differences were not statistically significant.
Conclusions: The results of this study were unable to support the detection of HPV in saliva rinses as a diagnostic method for OSCC.
Sahebjamee M, Boorghani M, Ghaffari SR, Atarbashimoghadam F, Keyhani A.
Department of Oral Medicine, Faculty of Dentistry, Tehran University of Medical Science, Tehran-Iran
Study design: The saliva sample of 22 patients with oral squamous cell carcinoma and 20 age-sex matched healthy controls were obtained. The presence of HPV 6, 11, 16, 18, 31, and 33 was evaluated by polymerase chain reaction (PCR).
Results: In 40.9% of the patients and in 25% of the controls, the saliva was shown to be positive for HPV. In 27.3% of the patients and in 20% of the controls, the saliva was shown to be positive for HPV16; and none of the controls, except one patient was shown to be positive for HPV 18. Neither patients nor controls were positive for HPV 31 and 33. These differences were not statistically significant.
Conclusions: The results of this study were unable to support the detection of HPV in saliva rinses as a diagnostic method for OSCC.
Sahebjamee M, Boorghani M, Ghaffari SR, Atarbashimoghadam F, Keyhani A.
Department of Oral Medicine, Faculty of Dentistry, Tehran University of Medical Science, Tehran-Iran
Salivary alpha-amylase as a longitudinal predictor of children's externalizing symptoms:
Department of Psychology, University of Kentucky, KY 40506, United States.
Salivary alpha-amylase (sAA) was examined as a predictor of children's externalizing symptoms cross-sectionally when children were in the 3rd grade (T1; N=64) and again in the 5th grade (T2; N=54) and longitudinally over two years. Parasympathetic nervous system (PNS) activity, indexed by respiratory sinus arrhythmia (RSA), was examined as a moderator of the sAA and child externalizing link. Participants were healthy, typically developing children, 34% of whom were African American and the rest European American. At each time point, saliva samples were collected during afternoon laboratory visits and assayed for sAA. Children's RSA was measured during baseline conditions and in response to an inter-adult argument and a star-tracing task. Cross-sectional associations between sAA and externalizing symptoms at T1 and T2 were moderated by PNS functioning. Longitudinally, sAA was directly associated with changes in externalizing symptoms in a non-linear fashion. Specifically, lower externalizing symptoms were predicted for children with moderate levels of sAA, but higher externalizing was predicted for children with higher or lower levels of sAA. Findings highlight the importance of the contemporaneous assessment of SNS and PNS functioning in the prediction of child psychopathology, and the need to examine curvilinear relations between ANS functioning and behavior
Salivary alpha-amylase (sAA) was examined as a predictor of children's externalizing symptoms cross-sectionally when children were in the 3rd grade (T1; N=64) and again in the 5th grade (T2; N=54) and longitudinally over two years. Parasympathetic nervous system (PNS) activity, indexed by respiratory sinus arrhythmia (RSA), was examined as a moderator of the sAA and child externalizing link. Participants were healthy, typically developing children, 34% of whom were African American and the rest European American. At each time point, saliva samples were collected during afternoon laboratory visits and assayed for sAA. Children's RSA was measured during baseline conditions and in response to an inter-adult argument and a star-tracing task. Cross-sectional associations between sAA and externalizing symptoms at T1 and T2 were moderated by PNS functioning. Longitudinally, sAA was directly associated with changes in externalizing symptoms in a non-linear fashion. Specifically, lower externalizing symptoms were predicted for children with moderate levels of sAA, but higher externalizing was predicted for children with higher or lower levels of sAA. Findings highlight the importance of the contemporaneous assessment of SNS and PNS functioning in the prediction of child psychopathology, and the need to examine curvilinear relations between ANS functioning and behavior
Salivary alpha-amylase, cortisol and chromogranin A responses to a lecture: impact of sex.
The aim of this study was to (1) examine the presence of stress on professors when they teach in front of 200 students and analyse objectively such stress using biomarkers such as salivary cortisol, chromogranin A (CgA) and alpha-amylase (AA) (2) investigate whether sex affects the reactivity of salivary alpha-amylase (sAA) and cortisol concentrations and the interaction of both hormonal systems. Fifty-two participants (26 women and 26 men) collected nine unstimulated saliva samples on 2 days, (one working day, and one resting day).
Cortisol concentrations and AA activity measured on the teaching day were significantly higher than those noted on the resting values. No differences between the resting day and the teaching day were reported for CgA. Our results showed a cortisol response to teaching, which was characterized by an anticipatory rise. The alpha-amylase level was significantly increased after the end of the lecture, and returned to the pre-lecture level 30 min after the end of the lecture.
The awakening cortisol response noted on the teaching day was significantly higher in females than in males. No baseline sex differences in sAA and CgA were observed and men and women seem to have a comparable reactivity in salivary alpha-amylase , CgA and cortisol levels on lecture stress. The mechanisms that leads to modify activity of salivary alpha-amylase and CgA due to stress is not entirely understood and further research is needed to elucidate them.
Laboratoire AMAPP, UFRSTAPS-2, Allée du Château, Orléans Cedex, France.
Cortisol concentrations and AA activity measured on the teaching day were significantly higher than those noted on the resting values. No differences between the resting day and the teaching day were reported for CgA. Our results showed a cortisol response to teaching, which was characterized by an anticipatory rise. The alpha-amylase level was significantly increased after the end of the lecture, and returned to the pre-lecture level 30 min after the end of the lecture.
The awakening cortisol response noted on the teaching day was significantly higher in females than in males. No baseline sex differences in sAA and CgA were observed and men and women seem to have a comparable reactivity in salivary alpha-amylase , CgA and cortisol levels on lecture stress. The mechanisms that leads to modify activity of salivary alpha-amylase and CgA due to stress is not entirely understood and further research is needed to elucidate them.
Laboratoire AMAPP, UFRSTAPS-2, Allée du Château, Orléans Cedex, France.
Salivary Proteomics for Oral Cancer Biomarker Discovery
Purpose: This study aims to explore the presence of informative protein biomarkers in the human saliva proteome and to evaluate their potential for detection of oral squamous cell carcinoma (OSCC).
Experimental Design: Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC.
Results: Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC.
Conclusion: Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers . The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer . Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
Shen Hu1, Martha Arellano1, Pinmanee Boontheung2, Jianghua Wang1, Hui Zhou1, Jiang Jiang1, David Elashoff7, Roger Wei1, Joseph A. Loo2,3,4 and David T. Wong1,3,5,6
Authors' Affiliations: 1 Oral Biology and Medicine Division and Dental Research Institute, School of Dentistry, 2 Department of Chemistry and Biochemistry, 3 Jonsson Comprehensive Cancer Center, 4 Department of Biological Chemistry, David Geffen School of Medicine, 5 Division of Head and Neck Surgery/Otolaryngology, School of Medicine, 6 Henry Samueli School of Engineering and Applied Science, and 7 Department of Biostatistics, School of Public Health, University of California at Los Angeles, Los Angeles, California
Experimental Design: Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC.
Results: Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC.
Conclusion: Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers . The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer . Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
Shen Hu1, Martha Arellano1, Pinmanee Boontheung2, Jianghua Wang1, Hui Zhou1, Jiang Jiang1, David Elashoff7, Roger Wei1, Joseph A. Loo2,3,4 and David T. Wong1,3,5,6
Authors' Affiliations: 1 Oral Biology and Medicine Division and Dental Research Institute, School of Dentistry, 2 Department of Chemistry and Biochemistry, 3 Jonsson Comprehensive Cancer Center, 4 Department of Biological Chemistry, David Geffen School of Medicine, 5 Division of Head and Neck Surgery/Otolaryngology, School of Medicine, 6 Henry Samueli School of Engineering and Applied Science, and 7 Department of Biostatistics, School of Public Health, University of California at Los Angeles, Los Angeles, California
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