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1.
Jpn Dent Sci Rev ; 59: 289-302, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37680614

ABSTRACT

In the era of 'precision medicine', liquid biopsies based on cell-free DNA (cfDNA) have emerged as a promising tool in the oncology field. cfDNA from cancer patients is a mixture of tumoral (ctDNA) and non-tumoral DNA originated from healthy, cancer and tumor microenvironmental cells. Apoptosis, necrosis, and active secretion from extracellular vesicles represent the main mechanisms of cfDNA release into the physiological body fluids. Focused on HNC, two main types of cfDNA can be identified: the circulating cfDNA (ccfDNA) and the salivary cfDNA (scfDNA). Numerous studies have reported on the potential of cfDNA analysis as potential diagnostic, prognostic, and monitoring biomarker for HNC. Thus, ctDNA has emerged as an attractive strategy to detect cancer specific genetic and epigenetic alterations including DNA somatic mutations and DNA methylation patterns. This review aims to provide an overview of the up-to-date studies evaluating the value of the analysis of total cfDNA, cfDNA fragment length, and ctDNA analysis at DNA mutation and methylation level in HNC patients.

2.
Rev Esp Enferm Dig ; 115(2): 59-63, 2023 02.
Article in English | MEDLINE | ID: mdl-36454105

ABSTRACT

MicroRNAs detected in liquid biopsies have demonstrated to have potential as biomarkers of benign and malignant bowel conditions. Numerous studies have reported on the combination of different microRNAs to improve the diagnostic capabilities in the detection of bowel conditions. This editorial will be reviewing the best scientific evidence available to this date on studies showing microRNA models with sensitivity and specificity values. Also, the current challenges on how to implement microRNAs in the routine clinical practice are exposed.


Subject(s)
Intestinal Diseases , MicroRNAs , Humans , MicroRNAs/genetics , Biomarkers, Tumor/genetics , Biomarkers , Liquid Biopsy , Sensitivity and Specificity
3.
Cancer Med ; 12(6): 6615-6622, 2023 03.
Article in English | MEDLINE | ID: mdl-36420687

ABSTRACT

BACKGROUND: We explore the utility of TruSight Tumor 170 panel (TST170) for detecting somatic mutations in tumor and cfDNA from locoregional recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: Targeted NGS of tumor DNA and plasma cfDNA was performed using TST170 panel. In addition, a set of somatic mutations previously described in HNSCC were selected for validating in tumor, plasma, and saliva by digital droplet PCR. RESULTS: The TST170 panel identified 13 non-synonymous somatic mutations, of which five were detected in tumoral tissue, other five in plasma cfDNA, and three in both tissue and plasma cfDNA. Of the eight somatic mutations identified in tissue, three were also identified in plasma cfDNA, showing an overall concordance rate of 37.5%. CONCLUSIONS: This preliminary study shows the possibility to detect somatic mutations in tumor and plasma of HNSCC patients using a single assay that would facilitate the clinical implementation of personalized medicine in the clinic.


Subject(s)
Cell-Free Nucleic Acids , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Head and Neck Neoplasms/genetics , High-Throughput Nucleotide Sequencing , Mutation , Biomarkers, Tumor/genetics
4.
Rev. esp. enferm. dig ; 115(2): 59-63, 2023. tab
Article in Spanish | IBECS | ID: ibc-215603

ABSTRACT

Los microARNs detectados en biopsias líquidas han demostrado tener potencial como biomarcadores en la patología intestinal benigna y maligna. Numerosos estudios han reportado la combinación de diferentes microARNs con el fin de mejorar la capacidad diagnóstica en patología intestinal. En esta editorial se pretende revisar la mejor evidencia disponible sobre estudios que muestran modelos de microARNs, con valores de sensibilidad y especificidad. También se exponen los desafíos que existen actualmente hasta poder llegar a implementar los microARNs en la clínica (AU)


Subject(s)
Humans , Colorectal Neoplasms/diagnosis , Liquid Biopsy , MicroRNAs/analysis , Biomarkers, Tumor/analysis , Sensitivity and Specificity
5.
Oral Dis ; 2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36398465

ABSTRACT

OBJECTIVES: To provide a comprehensive characterization of DNA methylome of oral tongue squamous cell carcinoma (OTSCC) and identify novel tumor-specific DNA methylation markers for early detection using saliva. MATERIAL AND METHODS: Genome-wide DNA methylation analysis including six OTSCC matched adjacent non-tumoral tissue and saliva was performed using Infinium MethylationEPIC array. Differentially methylated levels of selected genes in our OTSCC cohort were further validated using OTSCC methylation data from The Cancer Genome Atlas database (TCGA). The methylation levels of a set of tumor-specific hypermethylated genes associated with a downregulated expression were evaluated in saliva. Receiver operating characteristic (ROC) curves were performed to assess the diagnostic value of DNA methylation markers. RESULTS: A total of 25,890 CpGs (20,505 hypomethylated and 5385 hypermethylated) were differentially methylated (DMCpGs) between OTSCC and adjacent non-tumoral tissue. Hypermethylation of 11 tumor-specific genes was validated in OTSCC TCGA cohort. Of these 11 genes, A2BP1, ANK1, ALDH1A2, GFRA1, TTYH1, and PDE4B were also hypermethylated in saliva. These six salivary methylated genes showed high diagnostic accuracy (≥0.800) for discriminating patients from controls. CONCLUSIONS: This is the first largest genome-wide DNA methylation study on OTSCC that identifies a group of novel tumor-specific DNA methylation markers with diagnostic potential in saliva.

6.
Article in English | MEDLINE | ID: mdl-36293951

ABSTRACT

Forensic dentistry plays an important role in human identification, and dental age estimation is an important part of the process. Secondary dentin deposition throughout an individual's lifetime and consequent modification in teeth anatomy is an important parameter for age estimation procedures. The aim of the present study was to develop regression equations to determine age in adults by means of linear measurements and ratios on sagittal, coronal and axial slices of maxillary central incisors using cone bean computed tomography (CBCT). Multiplanar measurements of upper central incisors were taken for a sample of 373 CBCTs. Subsequently, one-way analysis of variance (ANOVA) and multivariate linear regressions were performed for age estimation. The equations obtained from axial linear measurements and ratios presented a standard error of the estimate (SEE) of ±10.9 years (R2 = 0.49), and a SEE of ±10.8 years (R2 = 0.50), respectively. The equation obtained for multiplanar linear measurements presented a SEE of ±10.9 years (R2 = 0.52), while the equation for multiplanar ratios presented a SEE of ±10.7 years (R2 = 0.51). Thus, CBCT measurements on upper central incisors were found to be an acceptable method for age estimation. Horizontal measurements, especially pulp measurements, improve the accuracy of age estimate equations.


Subject(s)
Age Determination by Teeth , Dentin, Secondary , Adult , Humans , Incisor/diagnostic imaging , Age Determination by Teeth/methods , Cone-Beam Computed Tomography/methods , Forensic Dentistry/methods
7.
Adv Exp Med Biol ; 1379: 525-552, 2022.
Article in English | MEDLINE | ID: mdl-35761006

ABSTRACT

Liquid biopsy has emerged as one of the main pillars for personalized oncology. The term englobes body-fluid samples which contain tumor-derived material such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating extracellular vesicles (cEVs). Potential clinical application of liquid biopsy analyses includes cancer screening, detection of minimal residual disease and recurrence, therapy selection, and evaluation of acquired resistance. Despite the great developments of technology focused on circulating biomarkers characterization only cfDNA testing is nowadays implemented for the therapy selection in some advanced tumors. This can be partially explained by the fact that there is still a lack of global standardization of procedures both in the pre-analytical and analytical steps. In the present chapter, we summarize the different strategies for addressing the study of liquid biopsy taking into account their pros and cons to be applied in a clinical context and we also discuss the main technical and clinical challenges in the field of circulating biomarkers and personalized oncology.


Subject(s)
Cell-Free Nucleic Acids , Circulating Tumor DNA , Neoplastic Cells, Circulating , Biomarkers, Tumor/genetics , Circulating Tumor DNA/genetics , Humans , Liquid Biopsy , Neoplastic Cells, Circulating/pathology
8.
J Oral Pathol Med ; 51(5): 429-435, 2022 May.
Article in English | MEDLINE | ID: mdl-35416334

ABSTRACT

BACKGROUND: Differences in cell-free DNA (cfDNA) fragments have been described as a valuable tool to distinguish cancer patients from healthy individuals. We aim to investigate the concentration and integrity of cfDNA fragments in saliva from oral squamous cell carcinoma (OSCC) patients and healthy individuals in order to explore their value as diagnostic biomarkers. METHODS: Saliva samples were collected from a total of 34 subjects (19 OSCC patients and 15 healthy controls). The total concentration of salivary cfDNA (scfDNA) was determined using a fluorometry method and quantitative real-time polymerase chain reaction (qPCR). To evaluate the scfDNA quantity and integrity, qPCR targeting Arthobacter luteus (ALU) sequences at three amplicons of different lengths (60, 115, and 247 bp, respectively) was carried out. ScfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) were calculated as the ratio between the absolute concentration of the longer amplicons 115 bp and 247 bp and the total scfDNA amount (amplicon 60 bp). RESULTS: The total scfDNA concentration (ALU60) was higher in OSCC than in healthy donors, but this trend was not statistically significant. The medians of scfDNA integrity indexes, ALU115/ALU60 and ALU247/ALU60, were significantly higher in OSCC, showing area under the curve values of 0.8211 and 0.7018, respectively. CONCLUSION: Our preliminary results suggest that scfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) have potential as noninvasive diagnostic biomarkers for OSCC.


Subject(s)
Carcinoma, Squamous Cell , Cell-Free Nucleic Acids , Mouth Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Saliva
9.
Article in English | MEDLINE | ID: mdl-34574666

ABSTRACT

The Dental Aesthetic Index (DAI) was determined in 12- and 15-year-old schoolchildren to ascertain the prevalence of malocclusion and to assess its association with dental caries experience, dental plaque accumulation, and socio-demographic variables. We performed a cross-sectional study with a stratified two-stage sampling design. An oral health survey and oral examination were conducted, and socio-demographic data were recorded. The sample comprised 1453 schoolchildren aged 12 (868) and 15 (585). These two samples were analyzed separately because statistically significant differences were found: the 12-year-old age group displayed a higher frequency of schoolchildren who attended state-run public schools (p = 0.004) and belonged to a lower social class (p = 0.001); the 15-year-old age group registered higher levels of caries (p = 0.001) and lower levels of dental plaque (p < 0.001). The malocclusion was 9.5% higher (p = 0.001), and the global mean DAI score was likewise higher among the 12-year-olds (p < 0.001). The multivariate regression analysis not only showed that caries and dental plaque were the variables that were the most strongly associated with malocclusion, but that caries (OR = 1.5) and dental plaque (OR > 2) were also risk factors for malocclusion in both groups. In conclusion, this study revealed a higher prevalence of malocclusion and dental plaque at age 12. A higher risk of caries and dental plaque was found to be related to the presence of malocclusion in both age groups.


Subject(s)
Dental Caries , Malocclusion , Adolescent , Child , Cross-Sectional Studies , DMF Index , Dental Caries/epidemiology , Esthetics, Dental , Humans , Malocclusion/epidemiology , Prevalence
10.
J Pers Med ; 11(6)2021 Jun 17.
Article in English | MEDLINE | ID: mdl-34204396

ABSTRACT

DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis.

11.
J Pers Med ; 11(7)2021 Jun 26.
Article in English | MEDLINE | ID: mdl-34206840

ABSTRACT

Aberrant methylation of tumor suppressor genes has been reported as an important epigenetic silencer in head and neck cancer (HNC) pathogenesis. Here, we performed a comprehensive meta-analysis to evaluate the overall and specific impact of salivary gene promoter methylation on HNC risk. The methodological quality was assessed using the Newcastle-Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association and Egger's and Begg's tests were applied to detect publication bias. The frequency of salivary DNA promoter methylation was significantly higher in HNC patients than in healthy controls (OR: 8.34 (95% CI = 6.10-11.39; p < 0.01). The pooled ORs showed a significant association between specific tumor-related genes and HNC risk: p16 (3.75; 95% CI = 2.51-5.60), MGMT (5.72; 95% CI = 3.00-10.91), DAPK (5.34; 95% CI = 2.18-13.10), TIMP3 (3.42; 95% CI = 1.99-5.88), and RASSF1A (7.69; 95% CI = 3.88-15.23). Overall, our meta-analysis provides precise evidence on the association between salivary DNA promoter hypermethylation and HNC risk. Thus, detection of promoter DNA methylation in saliva is a potential biomarker for predicting HNC risk.

12.
J Endod ; 47(8): 1215-1228, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33957175

ABSTRACT

INTRODUCTION: This study aimed to perform a systematic review and meta-analysis on accessory mental foramen (AMF) research using cone-beam computed tomographic (CBCT) imaging. METHODS: A systematic review was performed in PubMed, Embase, Thomas Reuter's Web of Science, Scopus, and ScienceDirect databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Articles focusing on AMF prevalence and location using CBCT imaging were selected without language restrictions. Studies reporting pooled results only or presenting any pathology in the area surrounding the mental foramen (MF) were excluded. A meta-analysis using random effects was performed. RESULTS: The present meta-analysis included a total of 46 articles involving 21,761 subjects. The overall pooled AMF prevalence was 7.87% (95% confidence interval [CI], 6.69-9.24) in subjects and 4.75% (95% CI, 3.79-5.95) in hemimandibles (n = 31,158). AMF presence was most commonly unilateral, reaching 90.15% (95% CI, 82.98-94.49). AMFs were significantly more frequent in right hemimandibles (χ2 = 5.20, P < .05) and were most commonly located posterior and inferior to the MF. However, AMFs superior to the MF were also observed in 47.43% (95% CI, 38.45-56.58) of cases. The studies conducted over the last 3 years showed significantly higher AMF prevalence levels (χ2 = 5.12, P < .05). CONCLUSIONS: Our meta-analysis demonstrates that AMF prevalence is considerable and should not be underestimated. AMFs are most frequently located in right hemimandibles. The presence of AMFs superior to the MF is frequent. Around 3% of people present superior AMFs. This fact puts those patients at greater risk for injury when performing periapical surgery in this area.


Subject(s)
Mental Foramen , Cone-Beam Computed Tomography , Diagnostic Tests, Routine , Humans , Mandible/diagnostic imaging , Prevalence
13.
J Clin Med ; 10(9)2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33947071

ABSTRACT

Oral carcinogenesis is a multistep process characterized by a summation of multiple genetic and epigenetic alterations in key regulatory genes. The silencing of genes by aberrant promoter hypermethylation is thought to be an important epigenetic event in cancer development and progression which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. Aberrant DNA methylation has been detected in different liquid biopsies, which may represent a potential alternative to solid biopsies. The detection of methylated genes in saliva may have clinical application for noninvasive oral cancer screening and early diagnosis. Here, we review the current evidence on gene promoter hypermethylation in saliva.

15.
J Clin Med ; 9(5)2020 May 01.
Article in English | MEDLINE | ID: mdl-32370055

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. METHODS: A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82-8.67), oral cancer (OR = 2.58; 1.67-3.99) and oropharyngeal cancer (OR = 17.71; 6.42-48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65-27.82), oral cancer (OR = 2.95; 1.23-7.08) and oropharyngeal cancer (OR = 38.50; 22.43-66.07). CONCLUSIONS: Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator.

17.
Ann Med ; 52(3-4): 131-144, 2020.
Article in English | MEDLINE | ID: mdl-32056455

ABSTRACT

Background: Saliva represents a promising non-invasive source of novel biomarkers for diagnosis and prognosis cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the value of saliva as an alternative liquid biopsy.Materials and methods: We performed a systematic review and meta-analysis. PubMed, Embase, LILACS and the Cochrane Library were searched to identify articles that examined the potential of salivary biomarkers for the diagnosis of malignant non-oral tumours. To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR), area under hierarchical summary receiver operating characteristic (AUC) curve, sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) using a random- or fixed-effects model. Heterogeneity and publication bias were assessed. Statistical tests were two-sided.Results: One hundred fifty-five study units from 29 articles with 11,153 subjects were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.76 (95% confidence intervals (CI), 0.74-0.77), 0.76 (95% CI, 0.75-0.77), 3.22 (95% CI, 2.92-3.55), 0.31 (95% CI, 0.28-0.34), 13.42 (95% CI, 12.28-15.96) and 0.85 (95% CI, 0.84-0.87), respectively.Conclusion: Salivary biomarkers may be potentially used for non-invasive diagnosis of malignant non-oral tumours.Key messagesThis meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumours to better define the role of saliva as an alternative liquid biopsy.Salivary biomarkers showed 85% accuracy for cancer distant to the oral cavity.Saliva represents a promising non-invasive source of novel biomarkers in cancer.


Subject(s)
Neoplasms/diagnosis , Saliva/chemistry , Biomarkers, Tumor/analysis , Biopsy/methods , Humans , ROC Curve
18.
Cells ; 8(12)2019 12 17.
Article in English | MEDLINE | ID: mdl-31861130

ABSTRACT

Oral cavity cancer is the most frequent malignancy of the head and neck. Unfortunately, despite educational interventions for prevention and early diagnosis, oral cancer patients are often diagnosed in advanced stages associated with poor prognosis and life expectancy. Therefore, there is an urgent need to find noninvasive biomarkers to improve early detection of this tumor. Liquid biopsy has emerged as a valuable tool in medical oncology which provides new horizons for improving clinical decision making. Notably, cell-free microRNAs (miRNAs), a class of short non-coding RNAs, are emerging as novel noninvasive cancer biomarkers. Here, we provide an overview of the potential clinical application of cell-free miRNAs as diagnostic, prognostic, and therapeutic biomarkers in oral cancer.


Subject(s)
Biomarkers, Tumor/genetics , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Biomarkers, Tumor/blood , Biomarkers, Tumor/chemistry , Circulating MicroRNA/genetics , Humans , Liquid Biopsy/methods , MicroRNAs/genetics , Prognosis , Saliva/chemistry
19.
J Clin Med ; 8(12)2019 Nov 20.
Article in English | MEDLINE | ID: mdl-31757017

ABSTRACT

Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (P < 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (P < 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.

20.
Cancers (Basel) ; 11(7)2019 Jun 27.
Article in English | MEDLINE | ID: mdl-31252648

ABSTRACT

Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Despite numerous advances in therapeutic approaches, this cancer has a poor prognosis when it is diagnosed at late stages. Therefore, the scientific effort is nowadays directed towards the development of new non-invasive and dynamic biomarkers to improve the survival expectancy of CRC patients. In this sense, deregulated expression of many miRNAs has been shown to play an important role for CRC carcinogenesis and dissemination. Noticeably, an increasing number of studies highlight that circulating miRNAs, including those traveling inside exosomes or those released by tumor cells into circulation, constitute a promising tool for early detection, prognosis and therapy selection of CRC. Therefore, in this review we focus on the clinical potential of blood circulating miRNAs as emerging biomarkers with high value to improve the clinical management of CRC patients, providing a deep and complete perspective of the realities and challenges to translate these biomarkers to the clinical context.

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