Indicator In Oral Squamous Cell Carcinoma Research Articles

Association between lymph node ratio and survival outcomes in patients with oral squamous cell carcinoma

BackgroundRecent reports have shown that the Lymph node ratio (LNR) is useful for predicting the prognosis in some cancers, however there are few reports on the usefulness of LNR in predicting the prognosis of oral squamous cell carcinoma (OSCC). The predictive value of LNR for prognosis of OSCC was investigated. Materials and methodsThe study included 152 patients with OSCC and histologically confirmed cervical lymph node metastasis who underwent neck dissection. We analyzed the relationship between LNR and overall survival (OS) and recurrence-free survival (RFS) retrospectively in these cases, with the relationship between prognosis and clinicopathological findings also examined. ResultsUsing a receiver operating characteristics curve, the LNR cutoff value was set at 0.095, categorizing 64 and 88 cases into high LNR (≥ 0.095) and low LNR (< 0.095) groups, respectively. Regarding OS and RFS, the prognosis was significantly worse in the high LNR group compared with the low LNR group. In multivariate analysis, sex, postoperative nodal stage, and LNR merged as independent prognostic factors. ConclusionThis study's findings suggest that LNR may represent a prognostic indicator in OSCC with cervical lymph node metastasis.

Fibroblast growth factor receptors 1 and 4 combined with lymph node metastasis predicts poor prognosis in oral cancer.

The fibroblast growth factor receptor (FGFR) members including FGFR1-4 have been identified as promising novel therapeutic targets and prognostic markers in multiple solid tumors. However, the predictive role of the expression of FGFR proteins in oral squamous cell carcinoma (OSCC) requires further exploration. Immunohistochemical evaluation of FGFR1-4 was performed on 161 paired OSCC samples. The associations of FGFRs with clinicopathologic and prognostic parameters were analyzed. To further assess the contribution of FGFRs to OSCC proliferation, cell lines, and one PDX model was utilized to examine the anti-tumor effect of the pan-FGFR inhibitor AZD4547. All FGFR members were found to be overexpressed in OSCC tumors when compared to normal tissues, and their expression was significantly associated with poor overall survival and disease-free survival. Multivariate Cox regression analysis revealed high expression of FGFR1 (p = 0.014) and FGFR4 (p = 0.009) were independent prognostic factors and co-overexpression of FGFR1 and FGFR4 with lymph node metastasis increased HR for death (p = 0.02). The pan-FGFR inhibitor AZD4547 showed anti-tumor activity in cell lines and in a patient-derived xenograft of OSCC. This study highlights the co-overexpression of FGFR1 and FGFR4 as a significantly poor prognosis indicator in OSCC when combined with lymph node metastasis.

Development and Clinical Validation of a Novel 5 Gene Signature Based on Fatty Acid Metabolism-Related Genes in Oral Squamous Cell Carcinoma.

Lipid metabolism disorders play a crucial role in tumor development and progression. The aim of the study focused on constructing a novel prognostic model of oral squamous cell carcinoma (OSCC) patients using fatty acid metabolism-related genes. Microarray test and data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes related to fatty acid metabolism. The quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of targeted fatty acid metabolism genes. A risk predictive scoring model of fatty acid metabolism-related genes was generated using a multivariate Cox model. The efficacy of this model was assessed by time-dependent receiver operating characteristic curve (ROC). 14 fatty acid metabolism-related genes were identified by microarray test and TCGA database analysis and then confirmed by PCR. Finally, a 5 gene signature (ACACB, FABP3, PDK4, PPARG, and PLIN5) was constructed and a RiskScore was calculated for each patient. Compared to the high RiskScore group, the low RiskScore group had better overall survival (OS) (p = 0.02). The RiskScore derived from a 5 gene signature was a prognostic factor (HR: 3.73, 95% CI: 1.38, 10.09) for OSCC patients. The predictive classification efficiencies of RiskScore were evaluated and the area under the curve (AUC) values for 1, 3, and 5 years were 0.613, 0.652, and 0.681, respectively. Then we compared the predictive performance of the prognostic model with or without the RiskScore. The 5 gene-derived RiskScore can improve the predictive performance with AUC values of 0.760, 0.803, and 0.830 for 1, 3, and 5 years OS in prognostic model including the RiskScore. While the predicted AUC values of the model without RiskScore for 1, 3, and 5 years OS were 0.699, 0.715, and 0.714, respectively. We developed a predictive score model using 5 fatty acid metabolism-related genes, which could be a potential prognostic indicator in OSCC.

Peripheral blood values as predictors of autoimmune status in oral cavity squamous cell carcinoma

BackgroundRecent literature has highlighted the role of the host in prognosis in oral squamous cell carcinoma (OSCC). Autoimmune (AI) disease represents a macroscopic depiction of host status. The goal of this study was to predict an AI “status” and to analyze the utility of this “status” as a prognostic indicator in OSCC. MethodsFrom a departmental database of OSCC patients (n = 1377), 125 patients with an AI disorder were identified. PBL values were obtained and standardized for analysis. A LASSO regression model was used to determine the best predictors of AI status and an AI score was developed. The score was then analyzed across various survival endpoints. ResultsWhen AI score was divided into a binary variable, patients in the highest quartile had a significantly worse overall survival (OS), local recurrence-free (LRFP) and distant recurrence-free probability (DRFP). Survival curves showed significant differences for OS, DSS, LRFP, and DRFP. ConclusionsAI diseases are immune dysregulations that could play a role in prognosis. Therefore, development of an AI score is necessary to depict host status in a ubiquitous manner. AI score as a binary variable may be more utilitarian in a clinical setting, compared to the continuous score. This novel tool needs validation and integration into more tumor and host characteristics. This investigation showed utility of such a score, similar to PBL data in OSCC prognosis. Future studies should incorporate other relevant variables known to affect outcome and implement a more comprehensive predictive model.

Salivary Porphyromonas gingivalis predicts outcome in oral squamous cell carcinomas: a cohort study

BackgroundStudies suggest Porphyromonas gingivalis (Pg) increased the incidence of oral squamous cell carcinoma (OSCC). However, fimA genotypes distribution of Pg, the origination of Pg in tissue, and its prognostic value are inconclusive. We aimed to investigate the frequency of fimA genotypes in OSCC patients, study the association between Pg and OSCC, and explore the prognostic value of Pg.MethodsThe abundance of Pg in saliva from the OSCC group and the OSCC-free group was analysed by qPCR. The presence of Pg was explored in OSCC tissue and para-cancerous tissue by in situ hybridization. The frequency of fimA genotypes in saliva and OSCC tissue was determined by PCR, then PCR products were sequenced and compared. Clinical data were extracted, and patients followed up for a median period of 23 months. Clinicopathological variables were compared with the abundance of Pg using Pearson Chi-square test or Fisher’s exact test. The disease-free survival (DFS) rate was calculated by Kaplan–Meier method with log-rank tests.ResultsComparing the OSCC-free group, 95 patients with OSCC showed a high abundance of Pg in saliva (P = 0.033), and OSCC tissue showed strong in situ expression of Pg compared with paired normal tissue. Patients with OSCC showed a dominant distribution of Pg with genotype I + Ib (21.1%), II (31.6%), and IV (21.1%). FimA genotypes detected in saliva were in accordance with those in OSCC tissue, there was, moreover, a significant similarity in amplified Pg fragments. Of the 94 responsive OSCC patients, the recurrence rate was 26.6% (25/94). Overabundance of Pg in saliva showed advanced pathologic staging (P = 0.008), longer disease-free time (P = 0.029) and lower recurrence rate (P = 0.033). The overabundance of Pg in saliva was associated with improved disease-free survival (P = 0.049).ConclusionsThis study indicated that Pg might involve in the pathogenesis of OSCC, Pg carrying fimA I, Ib, II, and IV were prevalent genotypes in patients with OSCC, the provenance of Pg in OSCC tissue might be from the salivary microbial reservoir, and the abundance of Pg in saliva might consider as a favorable potential prognostic indicator in OSCC.

The CLINICOPATHOLOGICAL SPECTRUM OF ORAL SQUAMOUS CELL CARCINOMA AMONG TOBACCO CONSUMERS: AN INSTITUTIONAL STUDY

Background: Oral squamous cell carcinoma (OSCC) constitutes 90% of all oral malignancies. Tobacco products, viral infections and additional risk factors are common etiological elements for this tumor.&#x0D; Objective: The aim of this study is to analyze the clinicopathological and sociodemographic features of patients diagnosed with oral squamous cell carcinoma.&#x0D; Material and Methods: Histologically confirmed 35 OSCC cases were selected for study. The clinicopathological data was obtained from patients and analyzed using SPSS software version 20.&#x0D; Results: Majority of cases was men and diagnosed with disease during fourth decade of life. Buccal mucosa was the common site while gutka chewing was observed as leading habit among our cases. Also, stage II and moderate histological differentiation was predominant among prognostic indicators of OSCC.&#x0D; Conclusion: Our data suggested that men, gutka consumers and early onset of disease are more prevalent characteristics in oral squamous cell carcinoma cases from our population. Most tumors classically affected buccal mucosa and late diagnosis seems to be common among our cases.&#x0D; Keywords: Malignancy, Squamous Cell Carcinoma, Oral Cavity, Tobacco

Serum levels of 25-hydroxy-vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention.

ObjectivesSerum level of vitamin D has been used as a predictor for cancer development. We intend to measure the baseline vitamin D level in patients with oral squamous cell carcinoma (OSCC) and to compare same with non‐cancer controls to determine any association.Materials and methodsPatients with OSCC presenting to our clinics were included in this study. Their baseline serum vitamin D levels were measured prior to cancer treatment after obtaining their consents. These patients were then matched with at least 2 cancer‐free subjects to serve as controls and whose serum vitamin D levels were also measured. The serum vitamin D levels obtained for the two groups were then categorized into normal (>35 ng/ml), mild deficiency (25–35 ng/ml), moderate deficiency (12.5–25 ng/ml), and severe deficiency (<12.5 ng/ml). The data were analyzed statistically and the two groups compared.ResultsA total of 51 patients with OSCC (Male 22 [43%] and female 29 [57%]) and 113 cancer‐free controls (Male 36 [31.86%] and female 77 [68.14%]) were included in the study. The commonest site for OSCC was the tongue, accounting for 45% of the cancer cases. Mean age for cancer patients was 59.33 years ±12.54 and 49.24 years ±15.79 for the control. Among the OSCC patients, 74.51% had moderate to severe vitamin D deficiencies, whereas only 20.35% had a moderate deficiency in the control group with no severe deficiency.ConclusionLogistic regression analysis shows a positive association between vitamin D deficiency and OSCC risk especially in levels below 25 ng/ml. This further corroborates the assertion that vitamin D deficiency may be a useful indicator of OSCC. It may, therefore, be necessary to routinely prescribe vitamin D supplements to subjects with moderate to severe deficiencies in order to decrease the chances of OSCC development.

KRT84 is a potential tumor suppressor and good prognosis signature of oral squamous cell carcinoma.

Aims: Oral squamous cell carcinoma (OSCC) is a common oral cancer; however, current therapeutic approaches still show limited efficacy. Our research aims to explore effective biomarkers related to OSCC.Main methods: Gene expression profiles of paired OSCC tumor and paracancerous samples from The Cancer Genome Atlas (TCGA) were analyzed. mRNA and protein levels of KRT84 in OSCC cell line HSC-3 were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. KRT84 protein levels in OSCC tumor samples of different stages were determined by immunohistochemistry. Overall survival (OS) of OSCC samples was evaluated and association of multiple factors with OS was assessed.Key findings: Compared with paracancerous samples, 4642 DEGs were identified in OSCC tumor samples. Among them, KRT84 expression level in OSCC tumor tissues was obviously decreased, which was validated in HSC-3 cells. KRT84 expression level showed decreasing tendency with the increase of tumor grade and stage. Patients with low KRT84 expression level had inferior OS independently of multiple factors. Besides, antigen processing and presentation pathway were significantly activated in OSCC samples with high KRT84 expression. Elevated KRT84 mRNA as well as protein levels were confirmed by RT-qPCR and Western blot in OSCC and normal cell lines, and immunohistochemistry in OSCC tumor and paracancerous tissues.Significance: Our study suggests KRT84 as a tumor suppressor and good prognostic indicator for OSCC, which might be significant for OSCC diagnosis and treatment.

Quantitative analysis of microvessels density in different grades of oral squamous cell carcinoma

Background: Oral cancer is the sixth most common cancer in the world today. Angiogenesis plays a vital role in neoplasm growth and metastasis. It is modulated by both angiogenic stimulators and angiogenic inhibitors. Cluster of differentiation 31 (CD31) is expressed on endothelial cells and has been implicated in the adhesion and migration of endothelial cells during angiogenesis. Aims and Objectives: The aim and objectives of this study are to analyze the expression of CD31 in different histological grades of oral squamous cell carcinoma (OSCC), to determine the microvessel area (MVA) using a CD31 marker. Materials and Methods: The retrospective study was undertaken on 10 cases each of different grades of squamous cell carcinoma. Immunostaining using CD31 was used to demonstrate blood vessels. MVA was calculated using measurement tools in image analysis software and compared between the groups. One-way analysis of variance was used for comparing the parameter for multiple groups. Pairwise comparison of different grades of squamous cell carcinoma with the mean vascular area by Tukey's multiple analysis was done. Results: The mean vascular area decreased from well-differentiated squamous cell carcinoma to moderately differentiated carcinoma and was statistically significant (P ≤ 0.05) and increased from moderately differentiated squamous cell carcinoma to poorly differentiated squamous cell carcinoma and showed no statistical significance (P ≥ 0.05). Conclusion: Our study suggests that CD31 can be used as a prognostic indicator in OSCC.

Long non-coding RNA LINC00662 promotes proliferation and migration in oral squamous cell carcinoma.

BackgroundAlthough increasing evidence has demonstrated important roles for long non-coding RNAs (lncRNAs) in cancer development, their functions in oral squamous cell carcinoma (OSCC) growth remain largely unknown. Therefore, we aimed to investigate the role of LINC00662 in OSCC.MethodsThe expression of LINC00662 in 61 OSCC tissues and four OSCC cell lines were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and EdU staining methods. Migration and invasion abilities were analyzed using transwell and wound healing assay. Cell cycle distribution and apoptosis rate were evaluated by flow cytometry. Western blot method was performed to detect protein expression.ResultsWe found that the expression of LINC00662 was significantly increased in OSCC tissues, and a higher expression of LINC00662 was detected in larger tumor size, higher stage tumors and with lymph node metastasis. Moreover, overexpression of LINC00662 induced OSCC cell proliferation, increased migration and invasion abilities, and suppressed cell apoptosis. Knockdown of LINC00662 decreased the proliferation, migration, and invasion abilities of OSCC cell, and induced apoptosis. Furthermore, LINC00662 regulated the Wnt/β-catenin pathway.ConclusionOur data indicate that LINC00662 may represent a novel indicator of OSCC and may be a potential therapeutic target for diagnosis and therapy.

Letter to the editor: is HIF-1\u03b1 a viable prognostic indicator in OSCC? A critical review of a meta-analysis study

The study performed by Zhou et al. (World J Surg Oncol 15:104, 2017) titled “Clinical and prognostic significance of HIF-1α overexpression in oral squamous cell carcinoma: a meta-analysis” attempts to highlight hypoxia-inducible factor-1 alpha as a possible prognostic marker in oral squamous cell carcinoma (OSCC). We would like to underline a few points which may affect such a conclusion. The correlations between HIF-1α expression and tumour size as well as tumour stage are debatable. Further, the subgroup analysis incorporating Australia and Europe into a single subgroup limits the viability of the prognostic analysis of HIF-1α. We also suggest future studies in the same research area to analyse head and neck squamous cell carcinoma instead of OSCC, to ameliorate the limitations encountered by Zhou et al., due to the scarcity of relevant clinical data and a low number of studies about OSCC.

Prognostic impact of tumor-stroma ratio in oral squamous cell carcinoma - A pilot study.

Several prognostic indicators have been used for many decades in an attempt to predict clinical behaviour of Oral Squamous Cell Carcinoma (OSCC). The prognostic value of TSR is yet to be explored in OSCC. Hence, the aim of the present study was to evaluate the prognostic value of TSR in OSCC patients. A cohort of 60 histologically diagnosed cases of OSCC who underwent Radical Neck Dissection was included in the study. TSR was assessed and patients with >50% intratumor stroma were quantified as the stroma-poor group and those with <50% as the stroma-rich group. The parametric tests were performed for the statistical evaluation of TSR with the clinico-pathological variables and the survival. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 95.23% and 69.04%, respectively, in stroma-poor group and 77% and 44%, respectively in the stroma-rich group. TSR may serve as a reliable histologic prognostic indicator in OSCC and could be used in routine diagnostic pathology.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

Background:Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have “immuno-protective” effect, this remains unproven and various researchers have conflicting opinion.Aim:The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM.Study Design:It is a comparative retrospective study between two groups including 35 OSCC cases positive and 35 negative for LNM.Materials and Methodology:Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using “zigzag” method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue.Statistics:Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. The level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN and in tumor proper.Results and Conclusion:Our study showed weak positive correlation between mean eosinophils count in tumor and LNs which implies a definite association between the microenvironment of tumor, its progression and LNM. There was a significant association between MC density and decreased LNM also. We conclude that an increased number of immunological cells (TATE and MCs) are a favorable prognostic indicator in OSCC. There is evidence of reduction in LNM with increasing density of these immunological cells. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

Background:Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection, and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have “immuno-protective” effect, this remains unproven and various researchers have conflicting opinion.Aim:The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM.Study Design:It is a comparative-retrospective study between 2 groups including 35 OSCC cases positive and 35 negative for LNM.Materials and Methodology:Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using “zigzag” method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue.Statistics:Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. Level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN, and in tumor proper.Results and Conclusion:This study showed weak positive correlation between mean eosinophils count in tumor and LNs. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies. We conclude that an increased number of immunological cells are a favorable prognostic indicator in OSCC.

The expression of Bcl-2 in oral squamous cell carcinoma—A review

Currently, oral cancer is one of the most alarming health problems facing mankind. More than 90% of all oral cancers are oral squamous cell carcinoma (OSCC). BCL-2 proteins are one of the most prominent anti-apoptotic proteins expressed in OSCC. They contribute to cancer development and mediate resistance to current anticancer treatments. Various studies have been conducted to evaluate the expression of Bcl-2 in OSCC. This article emphasizes the importance of Bcl-2 expression as a prognostic indicator in OSCC.

Nuclear Fractal Dimensions as a Tool for Prognostication of Oral Squamous Cell Carcinoma.

Carcinogenesis follows complex molecular alterations, which are triggered by subtle chromatin architectural changes that are imperceptible to the human eye. As the treatment decisions in Oral Squamous Cell Carcinoma (OSCC) are hindered by the imprecise clinical stage determination and inter-observer variability in histological grading, focus in recent years has shifted to discovering identifiers related to neoplastic cell morphology studied through computer-aided image analysis. One such approach is the assessment of fractal geometry, a technique first described by Mandelbrot, which aids in precise assessment of architecture of natural objects. Assessment and quantification of degree of complexity of these fractal objects (self-similarities in structural complexity at different magnifying scales) is described as fractal dimension (FD). To evaluate the nuclear fractal dimension (NFD) in OSCC using computer-aided image analysis. Histological sections of 14 selected cases of Oral Squamous Cell Carcinoma (OSCC) and 6 samples of normal buccal mucosa (as control) were stained with Haematoxylin-Eosin and Feulgen stain for histopathological examination and evaluation of nuclear complexity respectively. Fifteen HPF at Invasive Tumour Front (ITF) and Tumour Proper (TP) of Feulgen-stained sections were selected and photographed in test and control samples. At ITF, TP and normal buccal mucosa 200 nuclei each were selected and analyzed using Image J software to quantify FD. The test and control groups were compared statistically using Independent sample t-test and One-way ANOVA. Nuclear FD increased progressively towards worst tumour staging as compared to normal buccal mucosa. Nuclear FD can be considered for quantification of nuclear architectural changes as a prognostic indicator in OSCC.