Detection Of Oral Squamous Cell Carcinoma Research Articles

Evaluating high-mobility group box 1 protein serum levels amongst Iranian patients with oral squamous cell carcinoma

ObjectiveMost patients with oral squamous cell carcinoma (OSCC) are diagnosed during advanced stages; hence, early detection programs might help the prognosis and survival rate. High mobility group box 1 protein (HMGB1) is a new biomarker, with possible association with the pathogenesis of human cancers. We aimed to investigate the diagnostic value of serum HMGB1 level amongst Iranian patients with OSCC. MethodsIn this cross-sectional study, HMGB1 serum activity was measured in 60 patients with OSCC and 60 eligible healthy individuals, using enzyme-linked immunosorbent assay (ELISA). The possible associations between the serological activity of HMGB1 and the clinicopathologic features of patients were also assessed. ResultsThe HMGB1 serum level in patients group (2514.1 ± 935.6 pg/mL) was significantly higher than the controls (508.7 ± 370.5 pg/mL) (p < 0.0001). This study demonstrated that the serum levels of HMGB1 were correlated with some of the features associated with a clinical advanced disease. A positive correlation was observed between HMGB1 level and tumor size (p = 0.038). HMGB1 level was significantly elevated in those with the lymph node involvement (p = 0.001), but no association was found with other clinicopathologic characteristics of OSCC patients, such as age, gender and different clinical stages (p > 0.05). ConclusionsThe HMGB1 levels in patient’s sera can be used as a diagnostic marker to detect OSCC. However, further studies with the larger sample size and longer follow-up are warranted to assess the potential of HMGB1 for the early detection of OSCC.

An insight into crystallization test

Crystallization test is based on the principle that, when a salt crystallizes out of an aqueous solution, the crystal growth is influenced by the presence of other substances in the solution, such as blood or plant extracts. If a mixture of copper chloride solution with a small amount of whole blood is allowed to crystallize under controlled experimental conditions, an aggregate of crystals forms. Crystallization method can be used as a diagnostic aid to provide information about the systemic conditions and general health of the patient. This study aims to study the patterns of crystallization and to further determine the efficacy of crystallization test as a screening modality in premalignant lesions and oral squamous cell carcinoma (OSCC). Fifty patients of OSCC, 50 patients of premalignant lesions, and 50 healthy individuals were selected. One drop of blood was collected from the study groups to perform crystallization using cupric chloride. Statistical analysis was performed using Chi-square test, Student's t-test (two-tailed), and analysis of variance. The different patterns of crystals formed were studied and statistically analyzed. Based on the study, it was concluded that Crystallization test can be used as an effective screening modality for detection of premalignant lesions and OSCC.

Extracellular matrix metalloproteinase inducer expression in histological grades of oral squamous cell carcinoma - An immunohistochemical study.

Background:Oral squamous cell carcinoma (OSCC) is the most common type of head-and-neck cancer. It is a complex and relentless malignancy prone to local invasion and dissemination. An insight into the molecular alterations associated with metastasis will provide critical insights into the fundamental mechanisms underlying its progression and further contribute to improvements in the clinical management of H and N cancer patients. Hence, identifying specific biomarkers would pave the way for early detection and prognosis of OSCC. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a membrane-bound glycoprotein found on the surface of tumor cells. It plays a central role in the promotion of tumor invasion, progression and metastasis as it upregulates matrix metalloproteinases secreted from adjacent fibroblasts. There is a paucity of studies on the expression of EMMPRIN in OSCC.Objectives:The aim is to assess the immunohistochemical expression of EMMPRIN in OSCC and to compare it with the clinicopathological parameters and histological grades of OSCC.Materials and Methods:Thirty histopathologically diagnosed cases of OSCC were included in the study. The slides were immunohistochemically analyzed for EMMPRIN expression and correlated with the clinicopathological parameters and histological grades of OSCC.Results:EMMPRIN expression was noted in all 30 cases of OSCC. Strong EMMPRIN expression was noted in the advanced clinical stages of OSCC. Higher histological grades of OSCC exhibited strong EMMPRIN expression.Conclusion:EMMPRIN overexpression indicates that this protein could be used as an important biological prognostic marker to identify high-risk OSCC patients.

An immuno-MALDI mass spectrometry assay for the oral cancer biomarker, matrix metalloproteinase-1, in dried saliva spot samples

Oral cavity cancer is a common cancer type that presents an increasingly serious global problem. Oral squamous cell carcinoma (OSCC) accounts for >90% oral cancer cases. No biomarker tests are currently available for management of this cancer type in clinical practice. Previously, we validated matrix metalloproteinase-1 (MMP1) as one of the most promising salivary biomarkers for OSCC detection. Development of a convenient, rapid and high-throughput assay should further facilitate application of salivary MMP1 measurement for early detection of OSCC. The present study aimed to develop a workflow comprising dry saliva spot (DSS) sampling and immunoenrichment-coupled MALDI-TOF MS (immuno-MALDI) analysis to quantify salivary MMP1. We generated recombinant MMP1 protein and anti-peptide antibodies against MMP1, which were used to optimize the procedures of the entire workflow, including DSS sampling, on-paper protein digestion and elution, KingFisher magnetic particle processor-assisted immuno-enrichment and MALDI-TOF MS analysis. The established workflow was applied to measure salivary MMP1 levels in DSS samples from 5 healthy donors and 9 OSCC cases. The newly developed workflow showed good precision (intra-day and inter-day variations <10%) and accuracy (80–100%) in quantification of MMP1 in DSS samples, with the limit of quantification at 3.07 ng/ml. Using this assay, we successfully detected elevated salivary MMP1 levels (ranging from 5.95 to 242.52 ng/ml) in 7 of 9 OSCC cases while MMP1 was not detectable in samples from the 5 healthy donors. In comparison, the traditional immunoassay was not effective in measuring MMP1 in DSS samples, highlighting the significant advantage of our immuno-MALDI assay. The DSS sampling format confers high flexibility and convenience of collection, storage and delivery of saliva specimens and the KingFisher-assisted immuno-MALDI analysis renders the assay as suitable for high-throughput screening. By combining the two features, the workflow developed in this study should facilitate improvement of molecular diagnostic tests for OSCC using salivary MMP1 as a biomarker.

History and future perspectives for the use of fluorescence visualization to detect oral squamous cell carcinoma and oral potentially malignant disorders.

The early diagnosis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is challenging. The use of fluorescence visualization (FV) has been improved as an auxiliary method to early detect alterations in the oral mucosa suggestive of malignancy or pre-malignancy. However, perhaps due to some misinterpretation regarding the clinical purpose of this method, its applicability may have been underestimated. The purpose of this review is to comment on the challenges within the prevention and early diagnosis of OSCC and OPMDs; to contextualize the use of fluorescence-based methods in the diagnosis of human cancers; and to critically analyze the methods and results of studies that evaluated the FV to detect OSCC and OPMDs, and how this method might be applicable in the clinical practice. The current evidence available in the scientific literature indicates that the FV has the potential to improve the early detection of OSCC and OPMDs. Its use in primary healthcare by general practice dentists, oral hygienists, and oral health therapists is recommended, although more research in the population screening scenario is still required.

Saliva as a Non-Invasive Diagnostic Medium in Proteomics for Oral Squamous Cell Carcinoma Detection

Non-invasive diagnostic techniques are essential for the screening of oral cancer to reduce high mortality associated with it. The acknowledgement of various research advancements namely omic research and technological advances in the field of genomes has led to an increased use of saliva collection. Obtaining saliva for diagnosis is simple and non-invasive and is safe for both the health worker and the patient. It also permits easy and cost-effective storage methods. Around 3000 differently expressed proteins and peptides have been identified in various proteomic studies involving saliva, and hence, salivary proteomics is being progressively used for the early diagnosis of numerous diseases such as oral cancer, breast cancer, and several autoimmune disorders, among others. The salivary analysis riding on the recent advancements in technology, can prove to be of much more importance in near future.

Changes in oral microbial profiles associated with oral squamous cell carcinoma vs leukoplakia.

Oral squamous cell carcinoma (OSCC) is the most frequently occurring cancer among head and neck SCC worldwide. The identification of novel effective biomarkers for early detection may greatly improve the survival rate and prognosis of patients with OSCC. This study aimed to identify specific oral microbial profiles associated with OSCC. Saliva samples were collected from oral leukoplakia (OLK) and OSCC patients (N=6 each) and healthy controls (HC; N=4). Total bacterial genomic DNA was isolated and 16S rRNA gene survey was performed by next-generation sequencing of the V4 region. The relative distribution of abundance for phylogenetic groups was compared among the OSCC and OLK groups. The 448 operational taxonomic units detected from the libraries were classified into 133 genera, 69 families, 41 orders, 26 classes and 12 phyla. The abundance of phyla Bacteroidetes and genus Solobacterium was notably higher in the OSCC group when compared with the OLK group, whereas those of genus Streptococcus was significantly lower in the OSCC group when compared with the OLK. These changes in the salivary microbiome may have potential applications as a novel diagnostic tool for the early detection of OSCC.

The role of cyclin-dependent kinases in oral potentially malignant disorders and oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a major global health problem with a relatively low-moderate 5-year survival rate. OSCC is often preceded by lesions and conditions known as oral potentially malignant disorders (OPMDs) that have an increased risk of malignant transformation. Despite advances in diagnostic technology and cancer research, the prognosis of OSCC remains poor as it is frequently detected a late stage. Understanding the molecular pathways involved in oral carcinogenesis provides a platform to identify biomarkers that may allow the early detection of OSCC and accurate prediction of the malignant potential of OPMDs. In addition, specific molecular inhibitors can be developed to target these important pathways and allow advanced therapeutic management to improve the prognosis of this malignancy. A common feature across a number of different cancers is the dysfunction of cell cycle moderator proteins known as cyclin-dependent kinases. This review summarises the current literature regarding the role of cyclin-dependent kinases in oral carcinogenesis with a particular focus on cyclin-dependent kinases 4 (CDK4) and 6 (CDK6). This is of particular relevance as CDK4 and CDK6 inhibitors have shown some promising results in other cancer types and are interesting potential treatments for OSCC.

Increase in detection of oral cancer and precursor lesions by dentists: Evidence from an oral and maxillofacial pathology service

BackgroundDentists play an important role in the detection and diagnosis of oral diseases, including oral cancer and its precursor lesions. There are few comprehensive reviews in the recent literature that examine the scope and trends of oral disease diagnoses by dentists. MethodsThe authors analyzed all accessions to the Toronto Oral Pathology Service at the Faculty of Dentistry at the University of Toronto in Toronto, Ontario, Canada, from 2005 through 2015 using a custom-built database. They used these data to calculate the temporal trends in the diagnoses of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). ResultsA total of 63,483 biopsy specimens were submitted primarily by dentists from 2005 through 2015. From these, 2,679 cases of OED and 828 OSCC were diagnosed. The authors’ results show a 3.8-fold increase in the number of epithelial dysplasias and a 1.8-fold increase in mucosal carcinomas over the study period. The rate of increase of OED and OSCC was significantly higher than the rate of increase of total oral carcinomas diagnosed in the region, the population changes, and the number of dentists in the region. Conclusions and Practical ImplicationsWithin the limitations of a study of a single large oral pathology biopsy service, the analysis of diagnoses shows that dentists are increasingly involved in the detection of oral mucosal carcinoma and precursor lesions. The dental community plays an important and increasing role in the detection of oral cancer and potentially malignant disorders. Increased awareness among oral health care and nonoral health care professionals may increase early detection of OSCC.

An unusual case of recurrent oral cancer in a young woman HPV-negative, non-smoker and non-drinker

An unusual case of recurrent oral cancer in a young woman HPV-negative, non-smoker and non-drinker

Plasma-Derived Inflammatory Proteins Predict Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a major concern with high morbidity and mortality worldwide, even with the current knowledge and the advancement in treatment. OSCCs diagnosed at late-stage often require wide-excision with or without neck dissection, radiotherapy, or chemotherapy. When deemed successful, treatment often results in diminished quality of life, impaired function, and disfigurement. Strategies for early detection are urgently needed for patients afflicted with this disease. Inflammatory protein plasma biomarkers have shown to be potential tests for early detection and disease monitoring in several cancers. There has been no study on inflammation-related plasma biomarkers in OSCC. The objectives of the study were to use a multiplex approach to screen plasma-derived biomarkers and to examine the association of measurable proteins with OSCC. A total of 260 plasma samples (210 OSCC and 50 normal controls) were collected to measure for concentration of inflammatory related biomarkers using electrochemiluminescence multiplex assay. After screening of 82 potential biomarkers of the first 160 OSCC, 16 cytokines, chemokines, and growth factors were identified and verified in the second set of samples containing 50 OSCC and 50 normal. After adjustment of age and batch effects, the adjusted differential expression analysis showed that the OSCCs were markedly lower in 14 biomarkers and significantly higher level of interleukin 1 receptor antagonist (IL1Ra). By performing unsupervised clustering analysis, we observed distinctive groups of normal and two subgroups of OSCC. Linear regression of IL2, IL1Ra, and macrophage inhibitory factor (MIF) showed high accuracy in classifying OSCC with sensitivity of 0.96 and specificity of 0.92. In conclusion, this is the first paper to identify potential inflammatory plasma protein biomarkers of patients with OSCC. With further validation, the set of biomarkers can potentially be used to assist in early detection of OSCC when the disease is localized and in more treatable stage.

Mediators of Inflammation - A Potential Source of Biomarkers in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common tumour of the oral cavity, associated with significant morbidity and mortality. It is a multifactorial condition, both genetic and environmental factors being involved in its development and progression. Its pathogenesis is not fully elucidated, but a pivotal role has been attributed to inflammation, strong evidence supporting the association between chronic inflammation and carcinogenesis. Moreover, an increasing number of studies have investigated the role of different mediators of inflammation in the early detection of OSCC. In this review, we have summarized the main markers of inflammation that could be useful in diagnosis and shed some light in OSCC pathogenesis.

Salivary biomarkers and their efficacies as diagnostic tools for Oral Squamous Cell Carcinoma: Systematic review and meta-analysis.

More than 90% of malignant tumors of the head and neck are oral squamous cell carcinomas. Early detection of oral squamous cell carcinoma using salivary biomarkers could prevent malignant transformations and enhance patient survival. A systematic search in MEDLINE and the Central Register of Controlled Trials and meta-analysis were undertaken to identify the screening potential of six salivary biomarkers for early oral squamous cell carcinoma detection: interleukins IL-8 and IL1-β, DUSP-1 and S100P messenger RNAs, and miR125a and miR200a microRNAs. The sensitivities of IL-8 (0.41; 95%CI 0.19-0.99), IL1-β (0.26; 95%CI 0.19-0.99), DUSP-1 (0.61; 95%CI 0.01-0.98), and S100P (0.67; 95%CI 0.32-0.99) were calculated. Specificities of the biomarkers analyzed were found to be IL-8 (0.69; 95%CI 0.66-0.99), IL1-β (0.47; 95%CI 0.46-0.90), DUSP-1 (0.75; 95%CI 0.33-1), and S100P (0.73; 95%CI 0.18-0.99). Early detection of oral squamous cell carcinoma was best achieved by screening for salivary messenger RNA DUSP-1 and S100P. Further investigation is required into miRNAs as novel biomarkers.

An Overview on Current Non-invasive Diagnostic Devices in Oral Oncology.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, and despite advances in cancer therapies, the overall 5-year survival rate has remained below 50% over the past decades. OSCC is typically preceded by potentially malignant disorders (PMD), but distinguishing high-risk from low-risk PMD is challenging. In the last years, several diagnostic methods as light-based detection systems (LBDS) have been proposed to facilitate the detection of OSCC and PMD. Furthermore, the recent evolution of nanotechnology may provide new opportunities to detect PMD and OSCC at an early stage. Indeed, several preclinical studies showed the potential of nanotechnology to enhance diagnostic accuracy. For these reasons, it is fundamental to conduct studies to evaluate the efficacy of nanotechnology implementation in LBDS. The aim of this article is to review the current literature on LBDS and to provide a summary of the sensitivity and specificity of each technique, and possible future applications of nanotechnologies. The LBDS showed great potential for screening and monitoring oral lesions, but there are several factors that hinder an extensive use of these devices. These devices seem to be useful in assessing lesion margins that must be biopsied. However, to date, conventional oral examination, and tissue biopsy remain the gold standard for OSCC diagnosis. The use of nanotechnologies could be the next step in the evolution of LBDS, thus providing devices that can help clinicians to detect and better monitor oral lesions.

Combinatorial Characterization of Saliva for Oral Precancer Diagnostics

Background: Saliva based diagnostic can play an important role in the translational research related to cancer diagnostics and treatment. It is easily available, noninvasive, low storage cost, has less contamination chances with simple collection procedure. Cancers related to tobacco use, including oral cancer account for about 30% of all cancers in males and females. Five years' survival rate remains the same even after decades of advancement of detection, prevention, and treatment of OSCC (oral squamous cell carcinoma) mainly due to late diagnosis of oral potentially malignant disorders (OPMDs). Aim: Combinatorial characterization of saliva, endorsing multidimensional spectroscopic signatures using suitably designed biochamber. Methods: Eighteen saliva samples (6 normal, 6 OSF [oral submucous fibrosis, a type of OPMD] and 6 confirmed OSCC) were collected from GNIDSR (Guru Nanak Institute of Dental Science and Research) Kolkata. Ethical approval was obtained for the study and all the participants were explained the objectives of the study and a written informed consent was obtained from them. Participant's demographic detail and clinical characteristics were also recorded. The participants were asked not to consume food 1 hour before sample collection and were suggested to rinse their mouth 30 minutes prior to saliva expectoration to minimize the contamination of food in saliva. Empty, sterile, graded tubes were used for this purpose. The subjects were asked not to clear nose or throat during the process of saliva expectoration to avoid forced phlegm from other part of the respiratory tract. The saliva samples were then immediately transferred to −20 degrees and later in −80 degrees for long storage. The electrical impedance (EI) of saliva was measured in custom made biochambers with copper electrodes. The EI was measured for the frequency sweep from 20 Hz to 2 MHz using an impedance analyzer. Apart from EI measurement, the corresponding samples were subjected to FTIR (Fourier-transform IR spectroscopy) analysis. SPSS and OMNIC software were used for the data analysis of EI and FTIR respectively. Results: [Table: see text][Table: see text][Table: see text][ Table A , B &amp; C represents descriptive statistics, correlation matrix and component matrix respectively. The multivariate analysis of the FTIR data indicates the significant differences ( P &lt; 0.005) among the different study groups such as normal, OSF and OSCC. The eigen values (normal 0.917, OSF 0.962, OSCC 0.975) from component matrix analysis also indicate the same. Conclusion: The spectroscopic characterization (EI and FTIR) of saliva was effective in evaluating normal and OPMD condition. This noninvasive paradigm can serve as a complimentary technique to the existing gold standard methods for the early detection of oral cancer.

Promotor hypermethylated genes: Prospective diagnostic biomarkers in oral cancerogenesis

The advancements in epigenetics of oral squamous cell carcinoma (OSCC), are made in regard to DNA hypermethylation of MGMT, DAPK, ECAD (E-cadherin) and p16, as an important component of oral carcinogenesis and new potential biomarkers in molecular diagnostic strategies. The objective of the study was to evaluate the methylation status of the proposed genes and their possible role in the tumor genesis and diagnosis of OSCC. Materials and methods: From sixty surgically treated and molecularly analyzed patients, we obtained three groups of bioptical materials: tumor, normal contralateral and healthy tissues. Comparison of the frequencies of DNA methylation for all transcripts was utilized to validated their potential role in the cancerogenesis and detection of OSCC. Results: The most often methylated genes in the tumor samples were ECAD, MGMT, DAPK followed by p16 genes (90% vs 75% vs 75% vs 52,5%), respectively. We observed frequent methylated genes in contralateral mucosa and consistently unmethylated- 0% in healthy samples. ECAD methylated genes showed the highest sensitivity for diagnosing OSCC in tumor and contralateral tissues (90% and 89,7% respectively, with a specificity of 100%). Conclusion: ECAD and MGMT have tumor-specific signatures and can be considered as potential noninvasive diagnostic biomarkers in OSCC.

Human leucocyte antigen-G 14-bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case-control study.

Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14-bp insertion/deletion (InDel) polymorphism in the 3' untranslated region (3'-UTR) of HLA-G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA-G (sHLA-G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR]=0.75; 95% confidence interval [CI]: 0.57-0.99; p=0.040). Distribution of the 14-bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR=0.57; 95% CI=0.33-0.99; p=0.044) and the log-additive model (OR=0.76; 95% CI: 0.58-0.99; p=0.044). The serum sHLA-G level was significantly higher in the OSCC patients than those in the healthy controls (p<0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA-G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856-0.925, p<0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA-G levels than those with Ins/Del and Del/Del genotypes (p=0.015). Furthermore, serum sHLA-G levels were significantly increased with the increasing TNM stages of the OSCC patients (p=0.017). Our findings revealed that the HLA-G 14-bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA-G may act as a promising biomarker for noninvasive diagnosis of OSCC.

Abstract 5123: Changes of oral microbiome profiles associated with oral squamous cell carcinoma

Abstract [Background] Oral squamous cell carcinoma (OSCC) is the most frequently occurring cancer among the head and neck SCCs worldwide. Despite significant efforts in OSCC research and advanced surgical treatments, radiotherapy, and chemotherapy, the 5-year overall survival rate has remained &amp;lt; 50% for the last few decades. OSCC prognosis remains poor due to late diagnosis. Therefore, clinically effective biomarkers for the early detection of OSCC can greatly improve the survival rate and prognosis. Approximately 15% of oral cancers cannot be explained by major risk factors, such as tobacco and alcohol use. A growing body of evidence supports an association between specific microorganisms, including those in the oral cavity, and various types of cancers. Because the role of bacteria in OSCC development has not been completely described, we investigated the changes in abundance of oral microbiota associated with OSCC. [AIMS] To identify the association between the oral microbiome and OSCC for the early detection and prevention. [Materials and methods] Unstimulated saliva samples were collected from 4 OSCC-free, 6 leukoplakia, and 6 OSCC subjects. Total bacterial genomic DNA from saliva was isolated, and 16S rRNA gene survey was performed by next-generation sequencing of the V4 region. The sequences were analyzed against reference sequences from the Human Oral Microbiome Database, and the relative abundance distribution for phylogenetic groups in 3 different libraries was compared. [Results] In total, 448 bacterial species from combined (OSCC-free, leukoplakia, and OSCC) libraries were detected, which were classified into 133 genera, 69 families, 41 orders, 26 classes, and 12 phyla. The frequency of phylum Bacteroidetes was more notably abundant in OSCC subjects compared with leukoplakia and OSCC-free subjects. In contrast, the abundances of genera Streptococcus and Rothia were significantly lower in OSCC subjects compared with leukoplakia and OSCC-free subjects using the Mann-Whitney U test. [Conclusion] This study revealed some OSCC-associated shifts in oral microbial communities. Salivary screening is suitable for the primary screening procedure because of its noninvasiveness and easy accessibility. Therefore, these changes in the saliva microbiome may have potential application as a useful diagnostic tool for the early detection of OSCC and malignant transformation of pre-cancerous regions. Citation Format: Kengo Hashimoto, Shuji Nomoto, Sho Hirabayashi, Sei Ueda, Ichiro Oh-iwa, Toru Nagao, Kazuo Shimozato. Changes of oral microbiome profiles associated with oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5123.

Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches

No effective screening method is available for oral squamous cell carcinoma (OSCC) that is recognized to influence by environmental factors as well as human papillomavirus (HPV) and Epstein-Barr virus (EBV). Therefore, we sought to identify salivary biomarkers for screening of OSCC with or without HPV and/or EBV infection. Saliva, lesion and oral exfoliated cells were collected from OSCC patients and cancer-free controls (CFCs) and grouped depending on their HPV- and EBV-infection status. Salivary protein was precipitated and subjected to 2-dimensional gel electrophoresis. Differential expression of proteins was identified by mass spectrometry and validated by Western blotting. Distinctive expression patterns of salivary proteins were detected in OSCC as compared with CFCs. Levels of peroxiredoxin-2 (PRDX-2) and zinc-alpha-2-glycoprotein (ZAG) were significantly up-regulated in OSCC cases (p<0.001) relative to CFCs. Similarly, these proteins were also up-regulated in lesion cells compared with oral exfoliated cells (p<0.001). However, the expression patterns of these proteins were not significantly influenced by patient histories (risk factors). In combination, these proteins yielded the highest discriminatory power (AUC=0.999), sensitivity (100%), and specificity (98.77%) in distinguishing the early stages of OSCC. The detection of PRDX-2 combining with ZAG protein could potentially be used as salivary biomarkers for early screening of OSCC. SignificanceOur findings demonstrate a useful of combined detection of PRDX-2 and ZAG as a salivary biomarker for the early detection of OSCC.

Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma

The aim of this study was to investigate potential biomarkers in human saliva and plasma to aid in the early diagnosis of oral squamous cell carcinoma (OSCC). Saliva and plasma samples obtained from OSCC patients (n=41) and non-oral cancer patients (n=24) were analyzed by Luminex Bead-based Multiplex Assay. Data were analyzed using the non-parametric Mann–Whitney U-test, Kruskal–Wallis test, and receiver operating characteristics curve (ROC) to evaluate the predictive power of 14 biomarkers individually for OSCC diagnosis. The plasma level of IP-10 in early OSCC differed significantly from that in controls. Among the salivary biomarkers, IL-1β, IL-6, IL-8, MIP-1β, eotaxin and IFN-γ and TNF-α showed significant differences between OSCC patients and controls. With respect to carcinogenesis, significant differences in plasma levels of eotaxin, G-CSF, and IL-6 were found between OSCC stages III/IV and OSCC stages I/II. The area under the curve (AUC) for OSCC vs. control was greater than 0.7 for plasma IP-10 and saliva IL-1β, IL-6, IL-8, and TNF-α. The study findings indicate that salivary biomarkers may serve a useful role as a complementary adjunct for the early detection of oral OSCC. With regard to the evaluation of tumour progression, plasma eotaxin, G-CSF, and IL-6 may help in the detection of advanced OSCC. However, the correlation between saliva and plasma biomarkers in OSCC was weak.