Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Differences among oral carcinomas arising de novo from those associated with oral potentially malignant disorders: a systematic review and meta-analysis.

OBJECTIVE: To analyze the frequency of sequential oral squamous cell carcinomas (s-OSCC), preceded by oral potentially malignant disorders, and OSCC de novo (OSCC-dn) and explore differences in their clinicopathologic presentations. STUDY DESIGN: A structured electronic search strategy identified studies that analyzed frequency, clinical, biological, demographic, biomarkers, and prognostic features of s-OSCC and OSCC-dn according to PRISMA guidelines in PubMed, Scopus, Cochrane Library, and Google Scholar, up to January 31, 2023. Inclusion criteria were original English, Spanish, Portuguese, French, Italian, and German cross-sectional, cohort, and case-control studies. The quality of studies was assessed using the Agency for Research and Health Quality tool and the Newcastle-Ottawa Scale tool. RESULTS: The final selection included 40 studies. OSCC-dn and s-OSCC represent, respectively, 71% and 29% of cases of OSCC (P = .00), showing a higher percentage of T1 or of T1+T2 in s-OSCC (P < .0001). The association meta-analysis showed OSCC-dn with a significant association. The meta-analysis showed that s-OSCC was significantly associated with smaller tumor size, absence of distant metastases, relapses, male sex, and tumor sites different from tongue; and OSCC-dn was associated with more advanced tumor size, more regional and distant metastases, more advanced stages, and worse survival. CONCLUSIONS: S-OSCC was less frequent than expected. OSCC-dn seems to have specific clinical, biological, and prognostic features. Future perspectives on oral cancer prevention should address novel approaches and alternatives to screening, such as urgent referral of OSCC-dn.

Potential Single Nucleotide Polymorphisms markers for radiation dermatitis in head and neck cancer patients: a meta-analysis.

PURPOSE: To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD. METHODS: This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE. RESULTS: Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFß1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with a similar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed a statistically significant association with very low certainty of evidence. CONCLUSION: The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be a promising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have a customized treatment. This current review provides new research directions.

Peptidomics Strategies to Evaluate Cancer Diagnosis, Prognosis, and Treatment.

Peptides have potential bioactive functions, and the peptidomics landscape has been broadly investigated for various diseases, including cancer. In this chapter, we reviewed the past four years of literature available and selected 16 peer-reviewed publications exploring peptidomics in diagnosis, prognosis, and treatment in cancer research. We highlighted their main aims, mass spectrometry-based peptidomics, multi-omics, data-driven and in silico strategies, functional assays, and clinical applications. Moreover, we underscored several levels of difficulties in translating the peptidomics findings to clinical practice, aiming to learn with the accumulated knowledge and guide upcoming studies. Finally, this review reinforces the peptidomics robustness in discovering potential candidates for monitoring the several stages of cancer disease and therapeutic treatment, leveraging the management of cancer patients in the future.

Proteomics of serum-derived extracellular vesicles are associated with the severity and different clinical profiles of patients with COVID-19: An exploratory secondary analysis.

BACKGROUND AIMS: Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical manifestations with the potential to progress to multiple organ dysfunction in severe cases. Extracellular vesicles (EVs) carry a range of biological cargoes, which may be used as biomarkers of disease state. METHODS: An exploratory secondary analysis of the SARITA-2 and SARITA-1 datasets (randomized clinical trials on patients with mild and moderate/severe COVID-19) was performed. Serum-derived EVs were used for proteomic analysis to identify enriched biological processes and key proteins, thus providing insights into differences in disease severity. Serum-derived EVs were separated from patients with COVID-19 by size exclusion chromatography and nanoparticle tracking analysis was used to determine particle concentration and diameter. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to identify and quantify protein signatures. Bioinformatics and multivariate statistical analysis were applied to distinguish candidate proteins associated with disease severity (mild versus moderate/severe COVID-19). RESULTS: No differences were observed in terms of the concentration and diameter of enriched EVs between mild (n = 14) and moderate/severe (n = 30) COVID-19. A total of 414 proteins were found to be present in EVs, of which 360 were shared while 48 were uniquely present in severe/moderate compared to mild COVID-19. The main biological signatures in moderate/severe COVID-19 were associated with platelet degranulation, exocytosis, complement activation, immune effector activation, and humoral immune response. Von Willebrand factor, serum amyloid A-2 protein, histone H4 and H2A type 2-C, and fibrinogen ß-chain were the most differentially expressed proteins between severity groups. CONCLUSION: Exploratory proteomic analysis of serum-derived EVs from patients with COVID-19 detected key proteins related to immune response and activation of coagulation and complement pathways, which are associated with disease severity. Our data suggest that EV proteins may be relevant biomarkers of disease state and prognosis.

Burning mouth in oncology care: a systematic review.

Burning mouth, also referred to as oral dysesthesia, is an underreported condition among cancer patients that may represent an early symptom of cancer or an adverse effect of treatment. This review sought to characterize this symptom in oncology care where burning symptoms may occur. A systematic review of the literature was performed based on the PRISMA statement, and the protocol was registered at PROSPERO database. A structured search was done using eight databases. The process of study selection was conducted in two distinct phases. The JBI Critical Appraisal Tools were utilized to evaluate the risk of bias in the studies included. Of the total number of studies assessed, sixteen met the eligibility criteria. Of these studies included, 7 were case reports, 7 cross-sectional studies, and 2 non-randomized clinical trials. Most studies presented low risk of bias (n = 9), while the remaining studies were evaluated and scored as moderate (n = 5) or high (n = 2) risk of bias. Burning mouth was reported as a first symptom of cancer in three studies, and as an adverse event of radiotherapy (n = 2), chemoradiotherapy (n = 2), and chemotherapy (n = 9). Burning mouth was a first symptom in 0.62% of oral squamous cell carcinoma (OSCC), and 3.3% of patients with pain as chief complaint. Oral dysesthesia prevalence was 13.6% in patients experiencing chemotherapy-induced oral adverse events. The symptom of burning mouth should be examined in oncology care, as it may be underreported and therefore undertreated. New therapies may be related to a higher risk of oral burning and studies assessing approach to management are needed. Current management borrows from the current management of burning mouth in the non-cancer setting.

Clinical and epidemiological profile of burning mouth syndrome patients following the International Headache Society classification: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to determine the clinical and epidemiologic profile of patients with burning mouth syndrome (BMS) following the current classification of the International Headache Society (IHS)-the International Classification of Headache Disorders (ICHD-3) and the International Classification of Orofacial Pain (ICOP). STUDY DESIGN: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and involved a comprehensive search on PubMed, Scopus, EMBASE, Web of Science, LILACS, and the gray literature. RESULTS: Of the 4,252 studies identified, 41 were included. In general, there were no differences between the clinical and epidemiologic profiles of patients with BMS classified based on ICHD-3 or ICOP. Studies were pooled in meta-analyses and showed a significant prevalence of female patients between the sixth and seventh decade of life. The burning sensation and the tongue were the most prevalent descriptors and affected location. Significant associations were demonstrated between BMS and anxiety (P = .0006), depression (P = .004), and poor oral hygiene (P = .00001). CONCLUSIONS: Under the existing contemporary classification systems, patients with BMS were found to be mostly females in the sixth and seventh decade of life with a burning sensation on the tongue. Experiencing depression and anxiety was a commonly existing comorbidity.

Prevalence and clinical characteristics of oral lesions in heart transplant patients induced by sirolimus and everolimus: a systematic review and meta-analysis on a global scale.

OBJECTIVE: Sirolimus (SRL) and everolimus (EVL) are increasingly included in immunosuppressive protocols after heart transplantation. They present some side effects, including the appearance of painful lesions in the oral cavity. Therefore, this systematic review aimed to verify the global prevalence and clinical characteristics of oral lesions induced by SRL and EVL in heart transplant patients. STUDY DESIGN: A systematic review was performed using 5 main electronic databases (Medline/PubMed, SCOPUS, EMBASE, Web of Science, and LILACS), in addition to the gray literature. Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the Joanna Briggs Institute appraisal tools, and the certainty of evidence was evaluated through GRADE assessment. RESULTS: Seventeen studies (860 patients) were included in the qualitative analysis. Of these, 11 studies were pooled in a meta-analysis of prevalence. The worldwide prevalence of oral lesions induced by SRL and EVL in heart transplant patients was 10.0%, and most lesions were described as ulcers >1.0 cm, related to significant pain. CONCLUSIONS: Oral lesions induced by SRL and/or EVL, although not very prevalent, have a relevant impact on patient's lives and the continuity of treatment.

Pan-American prevalence of smokeless tobacco use and association with oral potentially malignant disorders and head and neck cancer: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of smokeless tobacco (SLT) use and its association with oral potentially malignant disorders (OPMDs) and head and neck cancer (HNC) in the Pan-American Health Organization (PAHO) region. STUDY DESIGN: A literature search was conducted across 9 databases and other sources. The eligibility criteria were pediatric (0-18 years old) and adult (19 years and older) populations consuming any type of SLT. Meta-analysis was performed to determine the prevalence of SLT and the association between its use and OPMDs/HNC in the PAHO region; the Grading of Recommendations Assessment, Development, and Evaluation tool was used to verify the certainty of evidence. RESULTS: Fifty-nine studies from 6 PAHO countries were included, of which 51 were also subjected to quantitative analysis. The pooled SLT prevalence of use was 15% (95%CI: 11.93-18.69) overall, 17% (95%CI: 13.25-22.65) in adults, and 11% (95%CI: 8.54-14.78) in the pediatric population. The highest reported SLT prevalence of use was 33.4% (95%CI: 27.17-39.93) in Venezuela. HNC was positively associated with SLT use (OR = 1.98, 95%CI: 1.54-2.55), with a moderate certainty of evidence. Among OPMDs, only leukoplakia reported a positive association with SLT use (OR = 8.38; 95%CI: 1.05-67.25). However, the quality of the evidence was very low. CONCLUSION: A high consumption of SLT use, chewing tobacco and snuff, is reported among the adult population residing in the PAHO region with a positive association with the development of oral leukoplakia and HNC.