Differential analysis of salivary microRNA profiles in healthy and chronic periodontitis patients using Next Generation sequencing technology.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE121910 | GEO | 2018/10/30
REPOSITORIES: GEO
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Project description:Pancreatic cancer is the fourth leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. Oral fluid (saliva) meets the demand for non-invasive, accessible, and highly efficient diagnostic medium. The level of salivary analytes, such as mRNA and microflora, vary upon disease onset; thus possess valuable signatures for early detection and screening. In this study, we evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for non-invasive detection of early pancreatic cancer. Two biomarker discovery technologies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 early pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. Importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This study comprehensively compared the salivary transcriptome and microflora between pancreatic cancer and control subjects. We have discovered and validated eleven mRNA biomarkers and two microbial biomarkers for early detection of pancreatic cancer in saliva. The logistic regression model with four salivary biomarkers can detect pancreatic cancer specifically without the complication of chronic pancreatitis. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. Keywords: Salivary biomarker, pancreatic cancer, early detection, salivary transcriptome, salivary microflora This study, which was approved by the UCLA Institutional Review Board, started sample collection in February 2006 and ended in April 2008. It had a discovery and verification phase, followed by an independent validation phase. All patients with clinically diagnosed early or locally advanced pancreatic cancer, chronic pancreatitis and matched healthy control were recruited from the UCLA Medical Center. The controls were matched for gender, age, ethnicity and smoking history. We chose early and locally advanced pancreatic cancers because they were considered early stage diseases. All patients were recently diagnosed with primary disease, and had not received any prior treatment in the form of chemotherapy, radiotherapy, surgery, or alternative remedies. No subjects had a history of prior malignancy, immunodeficiency, autoimmune disorders, hepatitis, or HIV infection. Written informed consent was obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were collected and processed as previously described. The saliva bank of pancreatic disease at the UCLA Dental Research Institute has collected 283 saliva samples since 2006. Of these, 114 samples, from 42 pancreatic cancer patients, 30 chronic pancreatitis patients and 42 healthy control subjects, met the following eligibility criteria: the disease subjectsâ?? samples were obtained immediately after primary diagnosis from patients without evidence of metastasis; the saliva sample was free of blood (Table 1 in accompanying manuscript). Of the 114 samples, 12 pancreatic cancer samples and 12 healthy control samples were chosen for the discovery and verification phase. The transcriptomic approach profiled the saliva supernatant samples from 12 pancreatic cancer patients and 12 healthy control subjects using the Affymetrix Human Genome U133 Plus 2.0 Array platform.
2008-12-30 | E-GEOD-14245 | biostudies-arrayexpress
Project description:The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. Thus, the purpose of the present investigation was to compare metaproteomic profiles of saliva in oral health and disease. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. Samples were analyzed by means of shotgun proteomics. 4161 different proteins were recorded out of which 1946 and 2090 were of bacterial and human origin respectively. The human proteomic profile displayed significant overexpression of the complement system and inflammatory mediators in periodontitis and dental caries. Bacterial proteomic profiles and functional annotation were very similar in health and disease. Data revealed multiple potential salivary proteomic biomarkers of oral disease. In addition, comparable bacterial functional profiles were observed in periodontitis, dental caries and oral health, which suggest that the salivary microbiota predominantly thrives in a planktonic state expressing no characteristic disease-associated metabolic activity. Future large-scale longitudinal studies are warranted to reveal the full potential of proteomic analysis of saliva as a biomarker of oral health and disease.
2017-03-29 | MSV000080763 | MassIVE
Project description:Periodontitis is a chronic inflammatory disease resulting from a dysbiosis of the dental biofilm and a dysregulated host response in susceptible individuals. It is characterized by periodontal attachment destruction, bone resorption, and eventual tooth loss. Salivary biomarkers have been sought to predict and prevent periodontitis. This comparative study analyzed the salivary proteome of 30 individuals with chronic periodontitis (CP) and 10 with periodontal health (PH), and correlated specific proteins with clinical parameters of disease by using mass spectrometry. Stimulated whole saliva was obtained and pooled for 5 healthy controls and 15 CP patients, precipitated with TCA, digested enzymatically with trypsin and analyzed by an LTQ Orbitrap Velos equipped with a nanoelectrospray ion source. A wide range of salivary proteins of various functions was significantly reduced in CP individuals, whereas salivary acidic proline-rich phosphoprotein, submaxillary gland androgen-regulated protein, histatin, fatty acid-binding protein, thioredoxin, and cystatin were predominant in diseased patients and correlated significantly with signs of periodontal attachment loss and inflammation. Specific salivary proteins were associated with PH and CP. These differences in salivary proteome profiles may contribute to the identification of disease indicators or signatures and the improvement of periodontal diagnosis.
2020-05-20 | PXD015024 | Pride
Project description:The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. Thus, the purpose of the present investigation was to compare metaproteomic profiles of saliva in oral health and disease. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. Samples were analyzed by means of shotgun proteomics. 4161 different proteins were recorded out of which 1946 and 2090 were of bacterial and human origin respectively. The human proteomic profile displayed significant overexpression of the complement system and inflammatory mediators in periodontitis and dental caries. Bacterial proteomic profiles and functional annotation were very similar in health and disease. Data revealed multiple potential salivary proteomic biomarkers of oral disease. In addition, comparable bacterial functional profiles were observed in periodontitis, dental caries and oral health, which suggest that the salivary microbiota predominantly thrives in a planktonic state expressing no characteristic disease-associated metabolic activity. Future large-scale longitudinal studies are warranted to reveal the full potential of proteomic analysis of saliva as a biomarker of oral health and disease.
2016-08-15 | PXD004319 | Pride
Project description:Tissue microRNAs (miRNAs) can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the diagnostic value of salivary miRNAs (including whole saliva and saliva supernatant) for detection of esophageal cancer. By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls.
2012-10-03 | E-GEOD-41268 | biostudies-arrayexpress
Project description:Pancreatic cancer is the fourth leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. Oral fluid (saliva) meets the demand for non-invasive, accessible, and highly efficient diagnostic medium. The level of salivary analytes, such as mRNA and microflora, vary upon disease onset; thus possess valuable signatures for early detection and screening. In this study, we evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for non-invasive detection of early pancreatic cancer. Two biomarker discovery technologies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 early pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. Importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This study comprehensively compared the salivary transcriptome and microflora between pancreatic cancer and control subjects. We have discovered and validated eleven mRNA biomarkers and two microbial biomarkers for early detection of pancreatic cancer in saliva. The logistic regression model with four salivary biomarkers can detect pancreatic cancer specifically without the complication of chronic pancreatitis. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. Keywords: Salivary biomarker, pancreatic cancer, early detection, salivary transcriptome, salivary microflora
2008-12-31 | GSE14245 | GEO
Project description:Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC. By Agilent microarray salivary miRNAs were profiled from saliva samples from 8 patients with resectable PC and 8 healthy controls. Candidate biomarkers discovered from the profile were subjected to validation by qPCR.
2013-12-15 | E-GEOD-53325 | biostudies-arrayexpress
Project description:The analysis of the salivary proteome of individuals with chronic periodontitis indicated that 21 differential proteins detected in saliva
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Project description:The goal of this study is to use a rapid method for oral neutrophil isolation and use a transcriptomics approach to characterize and compare the neutrophil gene expression profile in the blood and oral compartment of healthy individuals, chronic periodontitis patients and refractory periodontitis patients. Total RNA obtained from isolated neutrophils from blood and oral samples of Healthy patients, chronic periodontits patients and refractory periodontitis patients
2013-02-26 | E-GEOD-43525 | biostudies-arrayexpress
Project description:Periodontitis is characterized by the loss of the supporting tissues of the teeth in an inflammatory-infectious context. The diagnosis relies on clinical and X-ray examination. Unfortunately, clinical signs of tissue destruction occur late in the disease progression. Therefore, it is mandatory to identify reliable biomarkers to facilitate a better and earlier management of this disease. To this end, saliva represents a promising fluid for identification of biomarkers as metabolomic fingerprints. The present study used high-resolution 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis to identify the metabolic signature of active periodontitis. The metabolome of stimulated saliva of 26 patients with generalized periodontitis (18 chronic and 8 aggressive) was compared to that of 25 healthy controls. Principal Components Analysis (PCA), performed with clinical variables, indicated that the patient population was homogeneous, demonstrating a strong correlation between the clinical and the radiological variables used to assess the loss of periodontal tissues and criteria of active disease. Orthogonal Projection to Latent Structure (OPLS) analysis showed that patients with periodontitis can be discriminated from controls on the basis of metabolite concentrations in saliva with satisfactory explained variance (R2X = 0.81 and R2Y = 0.61) and predictability (Q2Y = 0.49, CV-AUROC = 0.94). Interestingly, this discrimination was irrespective of the type of generalized periodontitis, i.e. chronic or aggressive. Among the main discriminating metabolites were short chain fatty acids as butyrate, observed in higher concentrations, and lactate, gamma-amino-butyrate, methanol, and threonine observed in lower concentrations in periodontitis. The association of lactate, GABA, and butyrate to generate an aggregated variable reached the best positive predictive value for diagnosis of periodontitis. In conclusion, this pilot study showed that 1H-NMR spectroscopy analysis of saliva could differentiate patients with periodontitis from controls. Therefore, this simple, robust, non-invasive method, may offer a significant help for early diagnosis and follow-up of periodontitis.
2018-08-14 | MTBLS524 | MetaboLights