Unveiling the Potential of Serum MiR-483-5p: A Promising Diagnostic and Prognostic Biomarker in OLP and OSCC Patients by In silico Analysis of Differential Gene Expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.

An Insight into Survivin in Relevance to Hematological, Biochemical and Genetic Characteristics in Tobacco Chewers with Oral Squamous Cell Carcinoma.

BACKGROUND: Survivin is an inhibitor of apoptosis protein (IAP), encoded by the Baculoviral IAP Repeat Containing 5 (BIRC5) gene located on q arm (25.3) on chromosome 17. It is expressed in various human cancers and involved in tumor resistance to radiation and chemotherapy. The genetic analysis of the BIRC5 gene and its protein survivin levels in buccal tissue related to oral squamous cell carcinoma (OSCC) in South Indian tobacco chewers has not been studied. Hence, the study was designed to quantify survivin in buccal tissue and its association with pretreatment hematological parameters and to analyze the BIRC5 gene sequence. METHOD: In a single centric case control study, buccal tissue survivin levels were measured by ELISA. A total of 189 study subjects were categorized into Group 1 (n = 63) habitual tobacco chewers with OSCC, Group 2 (n = 63) habitual tobacco chewers without OSCC, and Group 3 (n = 63) healthy subjects as control. Retrospective hematological data were collected from Group 1 subjects and statistically analyzed. The BIRC5 gene was sequenced and data were analyzed using a bioinformatics tool. RESULTS: Survivin protein mean ± SD in Group 1 was (1670.9 ± 796.21 pg/mL), in Group 2 it was (1096.02 ± 346.17 pg/mL), and in Group 3 it was (397.5 ± 96.1 pg/mL) with significance (p < 0.001). Survivin levels showed significance with cut-off levels of absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR) at (p = 0.001). The unique variants found only in OSCC patients were T → G in the promoter region, G → C in exon 3, C → A, A → G, G → T, T → G, A → C, G → A in exon 4, C → A, G → T, G → C in the exon 5 region. CONCLUSIONS: The tissue survivin level increased in OSCC patients compared to controls; pretreatment AMC, LMR, and NLR may serve as add-on markers along with survivin to measure the progression of OSCC. Unique mutations in the promoter and exons 3-5 were observed in sequence analysis and were associated with survivin concentrations.

Holliday junction recognition protein as a prognostic biomarker and therapeutic target for oral cancer.

Since oral cancer (OC) is highly malignant and the efficacy of standard treatments is limited, the development of new therapeutics is urgently awaited. To identify potential molecular targets for new OC diagnosis and therapies, we screened oncoantigens by gene expression profile and focused on Holliday junction recognition protein (HJURP), a mammalian centromere­specific chaperone. HJURP was found to be highly expressed in the majority of OC cell lines and tissues as compared to normal oral epithelial cells. Tissue microarray analysis confirmed that HJURP was expressed in 103 (67.8%) of 152 OC tissue specimens, but expression in normal oral tissues was limited. Positive HJURP expression was significantly correlated with shorter overall survival (P=0.003). Depletion of HJURP by small­interfering RNAs dramatically inhibited the growth of OC cells by inhibition of cell cycle progression and induced senescence of OC cells. In addition, inhibition of the interaction between HJURP and CENP­A significantly suppressed the growth of OC cells. These results indicate that HJURP is a potential prognostic biomarker, and targeting HJURP and its molecular pathway presents a new strategy for the development of treatments against OC.

The impact of prehistoric human dispersals on the presence of tobacco-related oral cancer in Northeast India.

BACKGROUND: Northeast (NE) India is a subject of debate for predicting its involvement in prehistoric anatomically modern human (AMH) dispersal. The unique lifestyle and genetic characteristics of native ethnic groups in this region are believed to be responsible for their susceptibility to tobacco-related oral cancer (TrOC). The present study assessed mitochondrial macro-haplogroup (mHG) diversity and TrOC susceptibility autosomal loci to evaluate the impact of prehistoric AMH dispersal on the present day's high TrOC prevalence in major NE Indian ethnics. METHODS: We considered 175 unrelated individuals from 35 ethnic groups and previously published 374 sequences for sequencing-based assessment of mtDNA-based marker by subsequent analyses like haplogroup diversity, phylogenetic, genetic structure by AMOVA, and MDS, descriptive statistics of demographic parameters, and migration analysis. Besides, we selected prolonged tobacco-chewing 124 case-control individuals from similar ethnic backgrounds for genotyping 115 autosomal loci in Sequenom iPLEX MassARRAY™ platform and mined 1000genome data (n = 398) for consequent global admixture and ancestry-specific allele frequencies-based analyses. RESULTS: Our mtDNA-based findings suggested that NE populations were distinct from other Indian populations, owing to the first wave of migration from ancient southern China (∼54kya) and two successive spatial expansion events at âˆ¼45kya and âˆ¼43kya. Consequently, it probably acted as another source for prehistoric AMH dispersal in N/NE Asia. Besides, the second wave of back-migration from SE Asia (∼40kya) probably replaced the mitochondrial footprints of survivors from the first migrants and introduced the TrOC susceptibility traits in this region. Afterward, the autosomal marker-based observations on the transition of the disease-associated admixture component 'K6' from SE Asia reconfirmed these results. Moreover, we also observed that the mitochondrial mHG 'R' is significantly associated with the risk of TrOC (OR > 9.5) in NE India. Furthermore, the possible onset of the phenotypic expression of those traits was predicted at âˆ¼4kya, thus, contributing to present-day's TrOC prevalence. CONCLUSIONS: This study reflects its uniqueness by revealing an updated AMH dispersal route for the peopling in and out of NE India, which probably introduced the disease-causing traits in the ancestral NE Indian population. Those traits were then imprinted in their genome to get transferred through their respective generations, forming the present-day's TrOC-prevalent NE Indian population.

The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.

OBJECTIVE: Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. MATERIALS AND METHODS: The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. RESULTS: OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P < 0.0001, n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P < 0.0001), and were correlated with LNM (P < 0.0001) and PNI (P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. CONCLUSIONS: The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.

Parameters of Oxidative Stress, Vitamin D, Osteopontin, and Melatonin in Patients with Lip, Oral Cavity, and Pharyngeal Cancer.

Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research.

Cell-free DNA and circulating tumor cell kinetics in a pre-clinical head and neck Cancer model undergoing radiation therapy.

BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

Macrophage migration inhibitory factor: A promising oncogenic serological biomarker for oral squamous cell carcinoma.

There are few reports in oral squamous cell carcinoma (OSCC) that indicate the expression of macrophage migration inhibitory factor (MIF) in tissues, serum, or saliva of patients with OSCC. The aim of this study was to evaluate the mRNA expression and protein of MIF in tissues and serum, respectively, in OSCC patients and its association with the TNM stage. A cross-sectional study was performed. Serum and tissues of 25 patients with OSCC and 25 healthy control subjects (HCS) were included to evaluate the MIF mRNA expression and protein serum levels by real-time PCR and ELISA, respectively. Serum MIF levels were significantly higher in OSCC compared with control subjects. Furthermore, in the OSCC group, MIF was significantly increased in accordance with tumor disease stage (TNM III-IV), as well as in poorly differentiated tumors. The mRNA showed significantly higher levels in HCS, as well as in more differentiated tumors. The results of this study suggest that MIF could be an indicator of severity and progression of OSCC. Further studies are required to explore the role of MIF as a serological biomarker for OSCC.

Salivary melatonin in oral squamous cell carcinoma patients.

Melatonin's role in circadian rhythm is well documented, as are its' anti-oxidant, oncostatic and anti-inflammatory properties. Poor sleep quality has been associated as a potential risk factor for several malignancies, including head and neck cancers. The purpose of this study is to determine salivary melatonin (MLT) levels in oral squamous cell carcinoma (OSCC) patients, compare the salivary MLT levels with those in healthy individuals and compare the salivary and serum levels in OSCC patients. Furthermore, the aim is to investigate the potential relationship between sleep quality and salivary MLT levels in OSCC patients. Unstimulated (UWS) and stimulated (SWS) whole saliva was sampled from patients with T1N0M0 and T2N0M0 OSCC (N = 34) and 33 sex and age matched healthy subjects. Serum samples were taken from 11 OSCC patients. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) questionnaire. Melatonin levels in UWS and SWS were significantly higher in the OSCC group. Sleep quality was significantly lower in patients with OSCC (P = 0.0001). ROC analysis was found to be significant (P < 0.001) in evaluating MLT concentration limit in diagnosing OSCC. The expected relationship between sleep quality and salivary MLT levels in OSCC patients was not observed. Our results suggest salivary MLT as a potential biomarker that might facilitate non-invasive detection of early stage OSCC.

ABO Blood Groups and Its Association with Oral Cancer, Oral Potentially Malignant Disorders and Oral Submucous Fibrosis- A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aimed to evaluate the association between ABO blood groups and oral cancer, other potentially malignant disorders (OPMD), and oral submucous fibrosis (OSMF). MATERIALS AND METHODS: A search was conducted in Medline, Cochrane databases, Google Scholar, Scopus, Web of Science and Directory of Open Access Journals (DOAJ) for studies evaluating ABO blood groups as risk factors for oral cancer and OPMD among cases and controls. The PRISMA guidelines were followed for the meta-analysis. Participants included patients with oral cancer, and OPMD diagnosed using histopathologic investigations.  Sub-group analysis was conducted to evaluate the association between blood groups and OSMF. Quality was evaluated using the Risk of Bias Assessment tool. Fixed effects model was used to assess the odds ratio for the association. RESULTS: There were 1352, 414, and 299 cases of oral cancer, OPMD, and OSMF and 11,699, 7382 and 7307 controls for analysis respectively. Blood group A was significantly associated with both oral cancer (Odds ratio: 1.27 [95% CI, 1.10, 1.47], P= 0.001) and OPMD (Odds ratio: 1.33 [95% CI, 1.01, 1.47], P= 0.04).  No association was noted between blood group B and AB with oral cancer, OPMD, and OSMF. Blood group O was significantly associated with lower chances of oral cancer (Odds ratio: 0.81 [95% CI, 0.71, 0.93], P= 0.002). CONCLUSION: Meta-analysis suggests blood group A has a greater risk for developing oral cancer and OPMD. Blood group O was associated with lower chances of oral cancer. No association was noted between ABO blood group system with OSMF.

Characterization and ex vivo expansion of rare in situ cytokine secreting T cell populations from tumor tissue and blood of oral squamous cell carcinoma patients.

Rare subpopulations of tumor antigen-reactive memory T cells, which actively secrete type-1 effector cytokines, particularly TNF-α in situ, possess anti-tumor activity and prognostic relevance. These cells are relevant for cancer immunotherapy; however, their low frequencies make them difficult to study and novel protocols for their culture and expansion ex vivo are needed. Here, we studied the presence of T cells secreting type-1 cytokines (Cy+T cells) in the blood and tumors of 24 patients with oral squamous cell carcinomas (OSCC) and explored possibilities for their isolation and expansion. More than 90% of OSCC patients contained enriched numbers Cy+T cells in the blood and tumors compared to healthy donors in which these were hardly detectable. The majority of TNF-α+T cells were CD4+ T helper cells while IFN-γ+TIL were predominantly CD8+. Cy+T helper cells in the blood were early-differentiated memory T cells while Cy+TIL and Cy+CD8+T cells showed advanced-differentiated memory T cell phenotypes. We explored different conditions for their in vitro culture and found that Cy+T cells can be efficiently expanded in vitro to similar levels as Cy-T cells and after expansion maintained their TNF-α secreting capacity. However, for optimal expansion they required specific culture conditions to support the maintenance of stem-like and central memory T cell phenotype. In conclusion, we show that Cy+T cells are enriched in OSCC patients and report a novel cell culture protocol optimized to specifically expand and functionally maintain these cells for further functional characterization or for their exploitation in immunotherapy of OSCC.

Diagnostic efficacy of neutrophil to lymphocyte ratio (NLR) in oral potentially malignant disorders and oral cancer.

BACKGROUND AND AIMS: Inflammation is considered to be the seventh hallmark of cancer and plays a pivotal role in all stages of tumor development. Systemic inflammatory responses in particular neutrophil to lymphocyte ratio (NLR) have garnered immense attention of current researchers and its role is well proven in various solid malignancies. Its prognostic role in oral cancer have been extensively studied. However, its diagnostic role is yet to be explored. The current study aims to investigate diagnostic utility of NLR in oral potentially malignant disorders and oral cancer, when compared to normal subjects. METHODS: A total of 150 subjects were involved in the study, a total of 2.5 ml of blood was drawn from the median cubital vein of the patient in an EDTA vial and hematological parameters were assessed using Erba-Transasia B7256 Autoanalyzer and reassessed manually by two experts. STATISTICAL ANALYSIS: The NLR values were recorded and tabulated as Mean ± S.D. and comparisons were analyzed using Kruskal Wallis and Mann Whitney post hoc U test. ROC curve analysis was performed to estimate cut-off values. RESULTS: The NLR values when compared between the 3 groups were statistically significant (P < 0.001). The cut off value between disease and normal subject was 2.33, while the cut-off value between potentially malignant and malignant condition is 3.20. CONCLUSION: NLR can be a valuable diagnostic adjunct in oral cancer and potentially malignant disorders of oral cavity.

Association between the C-reactive protein/albumin ratio and prognosis in patients with oral squamous cell carcinoma.

The systemic inflammatory response is known to be associated with poor outcomes in patients with various types of cancer. The C-reactive protein (CRP)/albumin (Alb) ratio (CAR) has been reported as a novel inflammation-based prognostic marker. We have evaluated the prognostic value of inflammatory markers for patients with oral squamous cell carcinoma (OSCC). The study population included 205 patients treated with OSCC between 2013 and 2018. The primary predictor variable was the inflammatory markers. The primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify independent prognostic factors. The CAR had the highest area under the curve (AUC) values compared with other markers in the receiver operating characteristic (ROC) curve analysis. The cutoff value for CAR was 0.032 (AUC 0.693, P < 0.001). There was a significant difference in OS when patients were stratified according to CAR, with 79.1% for CAR < 0.032 and 35% for CAR ≥ 0.032 (P < 0.001). Cox multivariate analysis identified independent predictive factors for OS: age (hazard ratio [HR] 2.155, 95% confidence interval [CI] 1.262-3.682; P = 0.005), stage (HR 3.031, 95% CI 1.576-5.827; P = 0.001), and CAR (HR 2.859, 95% CI 1.667-4.904; P < 0.001). CAR (≥ 0.032 vs. < 0.032) is a good prognostic marker in patients with OSCC in terms of age and stage.

Estimation of Serum Midkine in Oral Squamous Cell Carcinoma and Oral Premalignancy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive epithelial malignancy. Diagnosis at an early stage is a key for successful cancer therapy. Development of sensitive, specific, and non-invasive tumor markers, especially, in serum, is needed. Midkine (MK) is a plasma-secreted multifunctional peptide which is a heparin-binding growth factor. MATERIALS AND METHODS: Blood samples were collected from 20 patients with OSCC, 20 patients with oral premalignancy and 10 healthy controls. Only histologically proven oral cancer and precancerous patients were taken as test subjects. Healthy individuals without predisposing habits were selected. The Human Midkine ELISA kit (Biovendor,Czech Republic) was stored at 2-80C. STATISTICAL ANALYSIS: One way ANOVA was applied using SPSS software. RESULTS: Midkine Concentration in Poorly differentiated was significantly higher than Well differentiated OSCC. Midkine Concentration in stage II was significantly higher than stage I. There was a very strong positive and significant correlation between severity of disease and Midkine concentration. Also there was a strong positive and significant correlation between histological grades of oral squamous cell carcinoma and Midkine concentration. INTERPRETATION AND CONCLUSION: MK is a soluble, secreted cytokine and can be quantitated in blood. This is a merit of any biomarker compared to biopsy, as sampling of blood is minimally invasive, convenient, inexpensive and can be performed frequently for detecting, monitoring and managing illness. Increased MK expression in tissues, blood and urine has a strong relationship with higher malignant potential. Serum MK concentration may serve for cancer screening and monitoring the prognosis of the disease.

Comparative prognostic value of different preoperative complete blood count cell ratios in patients with oral cavity cancer treated with surgery and postoperative radiotherapy.

BACKGROUND: We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). METHODS: We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. RESULTS: The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656-0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478-0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high-risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)-with a borderline significance being evident for DC in patients with T4 disease (p = 0.058). CONCLUSIONS: A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance.

Prognosis and predictive value of heat-shock proteins expression in oral cancer: A PRISMA-compliant meta-analysis.

BACKGROUND: Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer. MATERIALS AND METHODS: We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX). RESULTS: A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression. CONCLUSION: HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.

Identification of potential glycoprotein biomarkers in oral squamous cell carcinoma using sweet strategies.

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma.

BACKGROUND: The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. METHODS: We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. RESULTS: Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively). CONCLUSION: In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up.

Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma.

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

Role of miR153 and miR455-5p Expression in Oral Squamous Cell Carcinoma Isolated from Plasma.

BACKGROUND: Despite the notable advances in modern surgery and radiotherapy,no significant increase in the five year survival rate of oral squamous cell carcinoma has been reported. Collecting evidence demonstrates that miR 153 and miR 455-5p play a key role in growth and progression of oral cancer. Early detection of OSCC is important for enhancing patient quality of life and clinical treatment.For this reason, biomarkers or tumour markers offer an opportunity to intervene and avoid development of oral cancer. METHODS: A total of 50 blood samples from patients from both genders (25 OSCC and 25 healthy people/control groups) were obtained to determine the expression of miR153 and miR455-5p using Real time Polymerase chain reaction and t test. RESULTS: In general by using the formula Δ ct, it is evident that the miR 153 expression in peripheral blood is lower in patients than in healthy individuals (1.97) while the miR 455-5p expression in peripheral blood is higher in patients than in healthy individuals (2.56). CONCLUSION: We conclude that miR153 and miR 455-5p expression in serum can function as a diagnostic screening test for the early detection of oral squamous cell carcinoma.
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