scholarly journals Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer

2018 ◽  
Vol 64 (10) ◽  
pp. 1513-1521 ◽  
Author(s):  
Feng Li ◽  
Janice M Yoshizawa ◽  
Kyoung-Mee Kim ◽  
Julie Kanjanapangka ◽  
Tristan R Grogan ◽  
...  

Abstract BACKGROUND Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72–0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80–0.93). CONCLUSIONS We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

Author(s):  
Christina Winter ◽  
Roman Keimel ◽  
Markus Gugatschka ◽  
Dagmar Kolb ◽  
Gerd Leitinger ◽  
...  

The intact function of the salivary glands is of utmost importance for oral health. During radiotherapy in patients with head and neck tumors, the salivary glands can be damaged, causing the composition of saliva to change. This leads to xerostomia, which is a primary contributor to oral mucositis. Medications used for protective or palliative treatment often show poor efficacy as radiation-induced changes in the physico-chemical properties of saliva are not well understood. To improve treatment options, this study aimed to carefully examine unstimulated whole saliva of patients receiving radiation therapy and compare it with healthy unstimulated whole saliva. To this end, the pH, osmolality, electrical conductivity, buffer capacity, the whole protein and mucin concentrations, and the viscoelastic and adhesive properties were investigated. Moreover, hyaluronic acid was examined as a potential candidate for a saliva replacement fluid. The results showed that the pH of radiation-induced saliva shifted from neutral to acidic, the osmolality increased and the viscoelastic properties changed due to a disruption of the mucin network and a change in water secretion from the salivary glands. By adopting an aqueous 0.25% hyaluronic acid formulation regarding the lost properties, similar adhesion characteristics as in healthy, unstimulated saliva could be achieved.


Author(s):  
Kohei Fujimori ◽  
Toshiki Yoneda ◽  
Takaaki Tomofuji ◽  
Daisuke Ekuni ◽  
Tetsuji Azuma ◽  
...  

The aim of this two-year cohort study was to investigate salivary microRNAs (miRNAs) that predict periodontitis progression. A total of 120 patients who underwent supportive periodontal therapy were recruited. Unstimulated whole saliva was collected at baseline. Two years later, 44 patients were followed up (median age, 67.1 years) and divided into two groups: progression group (n = 22), with one or more sites with clinical attachment level (CAL) progression (>3 mm compared with baseline) or tooth extraction due to periodontitis progression; and the control group (n = 22), which did not exhibit CAL progression. In the microarray analysis of salivary miRNAs, hsa-miR-5571-5p, hsa-miR-17-3p, hsa-let-7f-5p, hsa-miR-4724-3p, hsa-miR-99a-5p, hsa-miR-200a-3p, hsa-miR-28-5p, hsa-miR-320d, and hsa-miR-31-5p showed fold change values <0.5 or ≥2.0 in the progression group compared with the control group (p < 0.05). On receiver operating characteristic curve analysis, areas under the curves of hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were >0.7, indicating fair discrimination power. The expressions of salivary hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were associated with periodontitis progression in patients with chronic periodontitis. These salivary miRNAs may be new biomarkers for progression of periodontitis, and monitoring them may contribute to new diagnostics and precision medicine for periodontitis.


2010 ◽  
Vol 135 ◽  
pp. S81
Author(s):  
Elissaveta Zvetkova ◽  
Georgi Kostov

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Merih T. Tesfazghi ◽  
Neil W. Anderson ◽  
Ann M. Gronowski ◽  
Melanie L. Yarbrough

ABSTRACT Manual treponemal and nontreponemal serologic testing has historically been used for the diagnosis of syphilis. This approach is simple and reproducible but labor intensive. Recently, the FDA cleared the fully automated BioPlex 2200 Syphilis Total & RPR assay for the detection of treponemal and nontreponemal antibodies. We evaluated the clinical performance of this assay at a tertiary medical center with a high syphilis prevalence. Prospective consecutively collected (n = 400) and known RPR-positive (n = 100) specimens were compared using predicate manual rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA) methods and the BioPlex 2200 Syphilis Total & RPR assay. Positive and negative percent agreements (PPA and NPA, respectively) between the assays were calculated. The PPA and NPA between the manual and BioPlex 2200 RPR results for the prospective population were 85% (17/20; 95% confidence interval [CI], 69% to 100%) and 98% (373/380; 95% CI, 97% to 99%), respectively. The PPA for the manual RPR-positive population was 88% (88/100; 95% CI, 82% to 94%). Overall, the manual and BioPlex 2200 RPR titers demonstrated 78% (99/127) concordance within ±1 dilution and 94% (120/127) within ±2 dilutions. An interpretation of the syphilis serologic profile using the traditional algorithm showed a concordance of 99.5% in the prospective population and 85% in the manual RPR-positive cohort. The performance of the BioPlex 2200 Syphilis Total & RPR assay is comparable to those of manual methods. The high NPA of this assay combined with the ability to automate a historically labor-intensive assay is an appealing attribute for syphilis screening in a high-volume laboratory.


2011 ◽  
Vol 6 ◽  
pp. BMI.S8326 ◽  
Author(s):  
Anna Gustafsson ◽  
Vjosa Ajeti ◽  
Lennart Ljunggren

The soluble urokinase plasminogen activator receptor (suPAR) has been detected in blood, plasma, serum, urine, ovarian cystic fluid, and cerebrospinal fluid. Elevated suPAR levels in plasma have been associated with negative outcomes in various diseases, such as bacteremia, sepsis, SIRS, cardiovascular disease, cancer, and tuberculosis. The primary aim of this study was to investigate whether suPAR can be detected in saliva from healthy individuals and thus, if saliva suPAR can be related to plasma suPAR, CRP, BMI, or gender. Blood and unstimulated whole saliva was collected from 20 healthy individuals (10 female and 10 male, median age of 28 years; range 21–41). CRP and suPAR were measured with ELISA in saliva and serum/plasma. suPAR was detected in all saliva samples in the 5.2–28.1 ng/mL range, with a median value of 17.1 ng/mL. Saliva suPAR was significantly higher ( P < 0.001) but not correlated to plasma suPAR in healthy young adults with normal plasma suPAR levels. suPAR and CRP levels were correlated in blood but not in saliva. No correlation was found between BMI, age, or gender and suPAR in saliva.


2018 ◽  
Vol 1 (1) ◽  
pp. 181-188
Author(s):  
Yumi Lindawati ◽  
Ameta Primasari ◽  
Dwi Suryanto

Fusobacterium nucleatum pada plak gigi berperan penting sebagai jembatan peralihan antara kolonisasi bakteri awal plak gigi dengan kolonisasi bakteri berikutnya, khususnya bakteri anaerob obligat. Fusobacterium nucleatum merupakan bakteri anaerob obligat, namun membran terluar F. nucleatum secara spesifik mengikat asam amino ke-21 dan 26 dari molekul staterin yang berasal dari saliva sehingga memungkinkan bakteri ini dapat tumbuh pada saliva dan plak supragingiva. Penelitian ini bertujuan untuk mengetahui keberadaan dan jumlah koloni F. nucleatum, konsentrasi staterin, korelasi keduanya pada saliva dan plak supragingiva. Penelitian observasional ini menggunakan desain cross- sectional pada 28 sampel Unstimulated whole saliva menggunakan metode spitting dan plak supragingiva matang dilekatkan pada paper point nomor 60 dari pasien di Instalasi Periodonsia RSGMP FKG USU. Konsentrasi staterin dihitung menggunakan ELISA, jumlah koloni F. nucleatum dengan mengkultur sampel pada media Crystal Violet Erythromicyn, dilakukan perhitungan manual pada piring petri. Penelitian ini menemukan pertumbuhan koloni F. nucleatum dari sampel saliva dan plak supragingiva dalam jumlah sedikit. Median konsentrasi staterin diperoleh pada saliva 1,5 µg/ml (x=2,35±2,71 µg/ml) pada plak supragingiva 223 µg/ml (x=332±242 µg/ml). Secara teoritis bakteri ini berhubungan dengan staterin, akan tetapi pada penelitian ini secara statistik tidak dapat dikorelasikan pertumbuhannya dengan staterin. Simpulan penelitian ini membuktikan bahwa F. nucleatum dapat diperoleh dari lingkungan yang mengandung oksigen seperti pada saliva dan plak supragingiva, akan tetapi keterkaitannya dengan staterin saliva pada lingkungan tersebut memerlukan penjelasan lebih lanjut. Fusobacteriumnucleatum on dental plaque plays an important role as a transitional bridge between early bacterial colonization of dental plaques and subsequent bacterial colonization, especially obligate anaerobes. Fusobacteriumnucleatum is an obligate anaerobic bacteria, but the outer nucleatum membrane specifically binds to the 21st and 26th amino acids from the statherin molecule which comes from saliva, allowing this bacteria to grow in saliva and supragingival plaque. The objective of this study was to determine the presence and the number of fusobacteriumnucleatum colonies, statherine concentrations, their correlation to saliva and supragingival plaque. This observational study used a cross-sectional design in 28 unstimulated whole saliva samples using spitting and mature supragingival plaque methods attached to number 60 paper points from patients at Installation Periodonsia RGGMP FKG USU. The concentration of statherin was calculated using ELISA, the number of F. nucleatum colonies by culturing samples on the Violet Erythromicyn Crystal media. Manual calculations were made on petri dishes. This study found small amounts of F. nucleatum colonies from saliva and supragingival plaque samples. The median statherine concentration was found at saliva 1.5 µg / ml (x = 2.35 ± 2.71 µg / ml) and at supragingival plaques 223 µg / ml (x = 332 ± 242 µg / ml). Theoretically, this bacteria is related to statherine, but its growth can not be statistically correlated with statherine in this study. The conclusion of this study proved that F. nucleatumcould be obtained from oxygen rich environment such as saliva and supragingival plaque, but its association with saliva in the temperature required further explanation.


2021 ◽  
Vol 45 (6) ◽  
pp. 414-420
Author(s):  
Alaa Sabah Hussein ◽  
Manal Mohamed Almoudi ◽  
Mohamed Ibrahim Abu-Hassan ◽  
Robert J Schroth ◽  
Bahruddin Saripudin ◽  
...  

Objective: Several studies have reported that low levels of vitamin D (25(OH)D) are associated with an increased risk of dental caries and that optimal levels may offer protection This study aimed to assess the relationship between serum and saliva 25(OH)D levels and caries among young children. Study design: A total of 120 healthy children were recruited; 93 with caries and 27 caries-free. Dental caries status was evaluated using decayed, missing and filled in primary teeth (dmft) index. Blood and unstimulated whole saliva samples were collected. Laboratory analysis was performed using Enzyme-Linked Immunosorbent Assay Kit. Data were analyzed with descriptive statistics, bivariate and Spearman’s rank correlation analysis. Results: There were no significant associations between serum and saliva 25(OH)D levels and caries status (P &gt; 0.05). Levels of 25(OH)D in serum were significantly higher than levels found in saliva (P &lt; 0.05), and a correlation between serum and saliva 25(OH)D levels was observed (P &lt; 0.05). Conclusions: The association between serum and saliva 25(OH)D and dental caries in young children was inconclusive. However, a positive and significant correlation was observed between serum and saliva 25(OH)D levels. Further studies are warranted to investigate the definite relation between 25(OH)D levels and dental caries and using saliva 25(OH)D as a non-invasive alternative method over blood samples.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Youn I Choi ◽  
Jun-won Chung ◽  
Kyoung Oh Kim ◽  
Kwang An Kwon ◽  
Yoon Jae Kim ◽  
...  

Backgrounds/Aims. Watson for Oncology (WFO) is a cognitive technology that processes medical information by analyzing the latest evidence and guidelines. However, studies of the concordance rate between WFO and clinicians for advanced gastric cancer (AGC) are lacking.Methods. We retrospectively reviewed 65 patients with AGC who consulted WFO and the Gachon Gil Medical Center multidisciplinary team (GMDT) in 2016 and 2017. The recommendations of WFO were compared with the opinions of the GMDT. WFO provided three treatment options: recommended (first treatment option), for consideration (second treatment option), and not recommended.Results. In total, 65 patients (mean age 61.0 years; 44 males and 21 females) were included in the study. The concordance rate between WFO and the GMDT was 41.5% (27/65) at the recommended level and 87.7% (57/65) at the for consideration level. The main causes of discordance between WFO and the GMDT were as follows. First, WFO did not consider the medical history. Second, WFO recommended the use of agents that are considered outdated in Korea. Third, some patients wanted to be involved in a clinical trial. Fourth, some patients refused to use the biologic agents recommended by WFO for financial reasons as they were not covered by medical insurance.Conclusions. The concordance rate at the recommended level was relatively low but was higher at the for consideration level. Discordances arose mainly from the different medical circumstances at the Gachon Gil Medical Center (GMC) and the Memorial Sloan Kettering Cancer Center (MSKCC), the main WFO consulting center. The utility of WFO as a tool for supporting clinical decision making could be further improved by incorporating regional guidelines.


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