Outcome Of Oral Squamous Cell Carcinoma Research Articles

The Molecular Basis and Therapeutic Aspects of Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a kind of malignant tumors with low survival rate and prone to have early metastasis and recurrence. Cisplatin is an alkylating agent which induces DNA damage through the formation of cisplatin-DNA adducts, leading to cell cycle arrest and apoptosis. In the management of advanced OSCC, cisplatin-based chemotherapy or chemoradiotherapy has been considered as the first-line treatment. Unfortunately, only a portion of OSCC patients can benefit from cisplatin treatment, both inherent resistance and acquired resistance greatly limit the efficacy of cisplatin and even cause treatment failure. Herein, this review outline the underlying mechanisms of cisplatin resistance in OSCC from the aspects of DNA damage and repair, epigenetic regulation, transport processes, programmed cell death and tumor microenvironment. In addition, this review summarizes the strategies applicable to overcome cisplatin resistance, which can provide new ideas to improve the clinical therapeutic outcome of OSCC.

The Hidden Treasures of Preoperative Blood Assessment in Oral Cancer: A Potential Source of Biomarkers.

Simple SummaryIn this study, we assess the prognostic potential of immune and inflammatory elements determined preoperatively in the peripheral blood of patients with oral squamous cell carcinoma (OSCC). Preoperative plasma fibrinogen (Fib) and platelet-to-lymphocyte ratio (PLR) show strong correlations with patients’ outcomes. Analyzed together, in a new parameter named Fibrinogen-PLR Algorithm (FiPLA), predictive power increases significantly. Clinicians can use this new, easy, cost-effective, and globally available tool for risk stratification of patients with OSCC, as early as from the moment of diagnosis.(1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p < 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232–67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC.

A Five-mRNA Expression Signature to Predict Survival in Oral Squamous Cell Carcinoma by Integrated Bioinformatic Analyses.

Objectives: This study was designed to identify a messenger RNA (mRNA) expression signature to predict survival in patients with oral squamous cell carcinoma (OSCC).Methods: mRNA expression profiles were integrated with clinical data from 280 samples, including 19 normal tissues and 261 OSCC tissues in The Cancer Genome Atlas. We identified differentially expressed mRNAs (DEmRNAs) between the OSCC and normal tissue samples and developed a novel mRNA-focused expression signature using a Cox regression analysis and other bioinformatic methods. The prognostic value of this signature was evaluated by Kaplan–Meier analysis, multivariable COX regression, and receiver operating characteristic (ROC) curve analysis. Protein–protein interaction (PPI) network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to predict the function of the DEmRNAs. Signature-related mRNAs were analyzed by gene set enrichment analyses (GSEA) and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 20 paired OSCC and adjacent healthy tissues.Results: We identified a novel 5-mRNA expression signature (HOXA1, CELSR3, HIST1H3J, ZFP42, and ASCL4) that could predict patient outcomes in OSCC. The risk score based on the signature was able to separate OSCC patients into high- and low-risk groups that showed significantly different overall survival (p < 0.001, log-rank test). The signature was further validated as an effective independent prognostic predictor of OSCC by multivariate Cox regression analysis (hazard ratio = 3.747, confidence interval: 2.279–5.677, p < 0.001) and ROC curve of the third year (area under the curve = 0.733). Functional analysis demonstrated that the key hub genes in the PPI network were mainly enriched in cell division, cell proliferation, and the p53 signaling pathway. GSEA results showed that the 5 mRNAs were significantly enriched in mismatch repair, DNA replication, and the NOTCH signaling pathway. Finally, qRT-PCR results showed that the 5 mRNAs were upregulated in OSCC tissue in agreement with the predictions from our bioinformatics analysis.Conclusions: We identified a novel 5-mRNA signature that could predict the survival of patients with OSCC and may be a promising biomarker for personalized cancer treatments.

Oral Squamous Cell Carcinoma Associated with Precursor Lesions.

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.

PROGNOSTIC IMPACT OF BRANDWEIN-GENSLER HISTOLOGIC RISK SCORE AND TUMOR-INFILTRATING LYMPHOCYTE SUBSETS IN ORAL SQUAMOUS CELL CARCINOMA

<h3>Background</h3> Despite improvements in treatment modalities, 5-year survival of oral squamous cell carcinoma (OSCC) is static. There is a shift in focus from tumor cell biology to tumor host interactions, which serve as novel, relatively unexplored avenues for identification of prognostic/predictive biomarkers. The Brandwein-Gensler Histological Risk Score (BG-score) is a scoring system based on parameters assessing tumor host interactions. Tumor-infiltrating lymphocytes (TILs) are the major immune cells in the OSCC microenvironment. <h3>Objective</h3> To assess the impact of BG-score and TIL subsets on patient outcomes in OSCC. <h3>Methods</h3> BG-score was calculated for 178 OSCC excisions and cases were classified into low-, intermediate-, and high-risk groups. Immunohistochemistry for TIL subsets was performed in 50 cases. Results were correlated with disease-free survival and overall survival. <h3>Results</h3> Twenty-five low-risk (14%), 93 intermediate-risk (52%), and 60 high-risk (34%) cases were identified. Two-year disease-free survival and overall survival were 22.5% and 34.8% for high-risk cases, 57% and 68.8% for intermediate-risk cases, and 96% and 96% for low-risk case. BG-score coupled with pathological stage had greater predictive value (78.8%) than BG-score (69%) or pathological stage (72.5%) alone. High CD8 count, low FOXP3 count, and CD8:FOXP3 ratio >1.46 were significantly associated with improved survival. <h3>Conclusions</h3> BG-score is a simple risk assessment technique with high prognostic impact. Tumor host immune response has a significant impact on prognosis, with increased CD8+ and low FOXP3+ cells being associated with improved outcome. A case is made for BG-score and TIL subset identification to be incorporated into routine histopathologic evaluation of OSCC as biomarkers for risk stratification and planning adjuvant treatment.

Histopathological Factors in Oral Squamous Cell Carcinoma—Should a Clinician Look Beyond Clinical Staging?

Several researchers have proposed and investigated the prognostic implications of various parameters, but have failed to provide concrete evidence regarding the inclusion or exclusion of histopathological features while clinically managing an oral squamous cell carcinoma (OSCC) case. The study purpose was to measure the prognostic values of a set of key histologic features and its association with its clinical outcome-5-year survival. This is a prospective cohort study and the sample was composed of patients treated for OSCC (April 2014 - March 2015). The predictor variables included pattern of tumor invasion (POI), stromal inflammation, angiogenesis, and vascular invasion with the outcome being survival of subjects observed over this 5-year period. Sociodemographic data (age, sex, marital status, systemic disease, habits etc), clinical staging and TNM staging were also recorded. We used multivariate regression analysis for predictor analysis; Kaplan-Meier survival curves and Cox hazard modeling was also performed using the data. This article includes 50 subjects with a mean age of 54.94years and 58% were male and their characteristics collected at the baseline and at a 12-, 24-, 36-, 48-, and 60-month follow-up. The overall 5-year survival was 48%. We saw a significant association between N-stage and POI (0.027), T-stage and mean vascular density (0.042), and T-stage and vascular invasion (0.046). POI, angiogenesis, and vascular invasion were found as significant predictors of overall 5-year survival (P<.001). This study shows that histopathological parameters such as POI are important while determining the clinical outcome of OSCC. Histopathological parameters such as angiogenesis and vascular invasion can provide valuable information about the overall survival and prognosis.

Epidemiology and pathology of oral squamous cell carcinoma in a multi-ethnic population: Retrospective study of 154 cases over 7 years in Qatar

BackgroundOral cancer (OC) is a neoplastic process of the oral cavity that has high mortality and significant effects on patients’ aesthetics. The majority of OC is oral squamous cell carcinoma (OSCC) and resection remains the most frequent treatment. Recurrence is the main cause of tumor-related mortality. Material and methodsA retrospective review of patients’ charts at Hamad Medical Corporation examined 154 adults who were diagnosed as OSCC and referred to the national head and neck cancer multi-disciplinary team meetings between 2012 and 2018. The data extracted was demographic, pathologic and clinical. All patients with oral cavity tumors other than squamous cell carcinoma were excluded. ResultsMales comprised the majority of the sample, mean age was 46.93 years. Tongue was the most common location. The majority of the patients were diagnosed at early stages, and a small subset of patients had histologically-proven local recurrence. ConclusionThe young male predominance of OSCC patients in Qatar is unprecedented worldwide. Most patients were non-Qataris, mainly from South Asia. Loss of follow-up was a challenge in assessing the long-term outcomes of OSCC. Our findings suggest the need for a more vigilant surveillance approach to oral lesions particularly in male South-Asian patients, as well as improving the follow-up strategies.

Lymphatic and vascular invasion in oral squamous cell carcinoma: Implications for recurrence and survival in a population-based cohort study

Numerous studies analyzed lymphovascular invasion (LVI) in various malignant diseases, however, little is known about the role of lymphatic invasion (LI) as well as vascular invasion (VI) in oral squamous cell carcinoma (OSCC). The aim of this study is to illuminate the role of LI and VI in a population-based cohort study. We retrospectively analyzed 745 primarily resected OSCC patients in Eastern Bavaria for histopathologically verified LI and VI. Overall survival (OS) and recurrence-free survival (RFS) were calculated, whereas analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.4years. LI was found in 115 patients (15.4%), VI was diagnosed in 23 cases (3.1%). LI correlated significantly with distinct anatomical sites (p=0.004), increasing pT-classification (p<0.001), lymph node involvement (p<0.001), higher grading (p<0.001), advanced UICC-stages (p<0.001) and adjuvant therapies (p<0.001). Similar results were found for VI. Survival analysis resulted in a significantly decreased five-year OS and RFS in patients with diagnosed LI (OS: 41.1%, RFS: 38.3%) in contrast to LI-negative cases (OS: 66.8%, RFS: 59.7.7%, p<0.001). Analogous outcomes were seen for patients with VI. Additionally, LI was identified as a predictive parameter, indicating individual patients' response to adjuvant therapies. This population-based cohort study underlines the unfavorable aspect of LI and VI on outcome in OSCC. Including LI and VI in existing staging systems could help to stratify patients' risk for adverse outcome and consecutively determine adjuvant treatment in malignant disease.

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Studies have found that circRNA in exosomes is associated with oral squamous cell carcinoma (OSCC) progression. In this study, we examined the expression of circ_0000199 in circulating exosomes from patients with OSCC and its role in the evaluation of relapse and prognosis. Real‐time quantitative reverse transcription–polymerase chain reaction was performed to assess circ_0000199 expression in circulating exosomes from 108 patients with OSCC and 50 healthy people. Gain- and loss-functional experiments were performed to assess the role of circ_0000199 on cell proliferation and apoptosis in OSCC cells. Our results showed that the high level of circ_0000199 in circulating exosomes was significantly associated with betel quid chewing, tumor size, lymphatic metastasis, and TNM stage in patients with OSCC. In addition, the patients with high exosomal circ_0000199 had higher tumor recurrence rate and higher mortality rate than the patients with low exosomal circ_0000199. Overexpression of circ_0000199 promoted, while knockdown of circ_0000199 inhibited OSCC cell growth. Bioinformatics analysis predicted that circ_0000199 interacted with miR-145-5p and miR-29b-3p simultaneously, which were involved in multiple tumor‐related signaling pathways. In conclusion, upregulation of circ_0000199 in circulating exosomes from patients with OSCC is positively associated with poor survival outcome. Circulating exosomal circ_0000199 can be used as a biomarker and potential therapeutic target for OSCC.

Lymph node ratio as a predictor for outcome in oral squamous cell carcinoma: a multicenter population-based cohort study

ObjectivesRecently, multiple studies addressed the importance of lymph node ratio (LNR) in specifying patients’ risk of disease recurrence in various malignancies. The present study examines the prognostic significance of LNR in predicting outcome of oral squamous cell carcinoma (OSCC) patients after surgical treatment with curative intent.MethodsHere, we describe a retrospective population-based cohort with 717 patients previously diagnosed with OSCC. Histopathologically verified lymph node metastasis was diagnosed in 290 patients. Among these patients, we evaluated the impact of LNR on overall survival (OAS) and recurrence-free survival (RFS) in uni- as well as multivariate analysis.ResultsA median cutoff (0.055) in LNR was found to significantly predict outcome in OSCC patients. Five-year OAS was 54.1% in patients with a low LNR, whereas a high LNR was associated with a 5-year OAS of 33.3% (p < 0.001). Similar results were detected for RFS with a 5-year survival rate of 49.8% (LNR low) and 30.3% (LNR high) (p = 0.002). Results were confirmed in multivariate Cox regression which substantiated the importance of LNR in predicting survival in OSCC patients.ConclusionsLNR was shown to be an independent prognostic factor for outcome of OSCC in a population-based cohort in uni- as well as multivariate analysis. Hereby, a LNR ≥ 0.055 predicted a shorter OAS and RFS in our cohort.Clinical relevanceBesides established histopathological factors, LNR can be used as a reliable predictor of outcome in OSCC and might therefore be further applied in evaluating adjuvant treatment after resection in curative intention.

The Role of miR-143, miR-145, and miR-590 in Expression Levels of CD44 and Vascular Endothelial Cadherin in Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with a continuing rise of incidence in developing countries. Despite the improvement in the clinical outcome of OSCC, the overall 5-year survival rate of patients is still disappointing. MicroRNAs (miRNAs) regulate gene expression in the post-transcriptional stage by targeting mRNAs. Advances in knowledge of the pathogenesis and molecular events lead to the improvement of OSCC treatments. Materials and Methods: Human oral epidermoid carcinoma cells (KB), HGF1, and HEK 293T cell line were cultured. Lentiviral vectors were constructed and Western Blot analysis was performed. Then, immunocytochemistry staining was performed by using CD44 and vascular endothelial cadherin (VE-Cadherin) antibodies. All data were analyzed using the REST 2009 software. P values of ≤0.05 were considered statistically significant. Results: MiR-143, miR-145, and miR 590 were down-regulated in the oral cancer cell line. Following transfection of Lv miR 143, Lv-miR-145, and Lv-miR-590, the expression of CD44 was markedly decreased in KB cells. In addition, transfection of miR-143 and miR- 590 mimics into the oral cancer cell line significantly decreased the expresion level of VE-Cadherin; however, transfection of miR-145 mimic had no significant effect on the expression of VE-Cadherin. Western blot analysis and immunocytochemistry staining confirmed the results. Conclusion: This study revealed that miR-143, miR-145, and miR-590 negatively regulate CD44 and VE-Cadherin (except miR-145) expression, which might play a crucial role in the induction of cancer stem cells proliferation and angiogenesis in OSCC cells. The knowledge about the involved factors may provide new insights for the clinical use of miR- 143, mR-145, and miR-590 in the treatment of patients with OSCC.

Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma

Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. A loss-of-function strategy using shRNA targeting STC2 was employed to investigate STC2 in vitro effects on proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) and possible activation of signaling pathways. Moreover, STC2 effects were assessed in vivo in a xenograft mouse cancer model. High expression of STC2 was significantly associated with poor disease-specific survival (HR: 2.67, 95% CI: 1.37–5.21, p = 0.001) and high rate of recurrence with a hazard ratio of 2.80 (95% CI: 1.07–5.71, p = 0.03). In vitro downregulation of STC2 expression in OSCC cells attenuated proliferation, migration and invasiveness while increased apoptotic rates. In addition, the STC2 downregulation controlled EMT phenotype of OSCC cells, with regulation on E-cadherin, vimentin, Snail1, Twist and Zeb2. The reactivation of STC2 was observed in the STC2 knockdown cells in the in vivo xenograft model, and no influence on tumor growth was observed. Modulation of STC2 expression levels did not alter consistently the phosphorylation status of CREB, ERK, JNK, p38, p70 S6K, STAT3, STAT5A/B and AKT. Our findings suggest that STC2 overexpression is an independent marker of OSCC outcome and may contribute to tumor progression via regulation of proliferation, survival and invasiveness of OSCC cells.

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) to examine 250 OSCC specimens in order to identify correlations between the cytoplasmic expression of ADAMTS14 and (1) clinicopathological features of OSCC as well as (2) clinical outcomes of OSCC. Our results indicate that cytoplasmic expression of ADAMTS14 was lower in OSCC tissues than in normal tissues. In analyzing correlations between ADAMTS14 expression and clinicopathological features, we found that negative cytoplasmic expression of ADAMTS14 was significantly associated with higher frequencies of lymph node metastasis and more advanced AJCC stages (III/IV). Kaplan–Meier survival analysis revealed that negative cytoplasmic expression of ADAMTS14 was also associated with significantly worse OSCC survival. Univariate and multivariate analyses confirmed that cytoplasmic expression of ADAMTS14 was associated with lymph node metastasis, tumor stage, and tumor grade and also indicated that cytoplasmic ADAMTS14 expression may be an independent prognostic factor for OSCC. This is the first study to report that the cytoplasmic expression level of ADAMTS14 is associated with OSCC prognosis and tumor progression. Our data indicate that ADAMTS14 can serve as a prognostic marker and a potential therapeutic target for OSCC.

MicroRNA-29b-3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway.

Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR‐29b‐3p as a guarder that suppressed migration and invasion of OSCC cells and was down‐regulated in the most invasive cells. Besides that, the invasion suppression role of miR‐29b‐3p was achieved through the IL32/AKT pathway. Thus, miR‐29b‐3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.

Expression of Kif5b protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma.

Kinesin family member 5b (Kif5b), a conventional kinesin, mainly participates in lysosome and mitochondria transportation. Some studies have indicated that Kif5b may be associated with the development of a variety of tumors. However, the role Kif5b plays in oral squamous cell carcinoma (OSCC) has yet to be determined. Our study aimed at investigating the expression level of Kif5b in primary OSCC and discussing its clinical significance in patients' outcomes. We measured Kif5b expression in 82 OSCC tissue samples with immunohistochemistry. The associations between the expression level of Kif5b and clinicopathological characteristics as well as patients' survival were statistically assessed. Kif5b level was significantly associated with tumor size (p=0.034), histological differentiation (p=0.028), disease recurrence (p=0.018), surrounding tissue invasion (p=0.045), recurrence time (p=0.036) and survival status (p=0.030). Kaplan-Meier cumulative survival analyses indicated that high expression of Kif5b was linked to worse overall survival (p=0.0112) and disease-free survival (p=0.0085). The univariate and multivariate Cox proportional hazard analysis further identified the expression status of Kif5b as an independent variable that correlated with patients' survival and recurrence. Furthermore, in 54 early-stage, clinically node negative OSCC patients, Kif5b expression were correlated with histological differentiation (p=0.034), disease recurrence (p=0.038) and surrounding tissue invasion (p=0.029). Univariate and multivariable logistic regression results showed that only Kif5b expression level could influence the probability of recurrence. Our results reveal that Kif5b expression is associated with poor clinical outcome in OSCC and even in early-stage, clinically node negative OSCC and may be a potential target for OSCC treatment.

Meta-analysis of the prognostic value of the neutrophil-to-lymphocyte ratio in oral squamous cell carcinoma.

A number of studies have assessed the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in oral squamous cell carcinoma (OSCC), but their results regarding the predictive value of NLR in OSCC are inconsistent. We therefore performed a meta-analysis to clarify the association between NLR and clinical outcome in OSCC. We searched the MEDLINE and Web of Science to identify potential studies investigating the association between NLR and survival in OSCC. A total of 10 studies, enrolling 2135 patients with OSCC, were included. A higher NLR was a negative predictor for both disease-specific survival (hazard ratio [HR]=1.93, 95% CI: 1.47-2.54) and overall survival (HR=1.56, 95% CI: 1.28-1.90). This suggests a higher NLR is predictive of a poorer prognosis in OSCC. Because determination of NLR is non-invasive and cost-effective, it could be widely used for predicting prognosis in OSCC.

Neutrophil-to-lymphocyte Ratio: A Surrogate Marker for Prognosis of Oral Squamous Cell Carcinoma

Abstract Context: Recent studies show that enzymatic contents of the neutrophil granules have a remarkable ability to modulate the tumor microenvironment by causing apoptosis of T-lymphocytes which leaves the host's cell-mediated immunity at stake. The preoperative neutrophil to lymphocyte ratio (NLR) is considered to be an indicator of the immune status of the patients with oral squamous cell carcinoma (OSCC), which will thereby help in predicting the course of the disease. Aims: The aim is to assess the NLR and histopathological prognostic factors pertinent to infiltration of the surrounding structures and correlate them with the clinical prognostic outcomes of OSCC. Settings and Design: This retrospective study involved the retrieval of formalin-fixed, paraffin-embedded, hematoxylin, and eosin-stained sections of 55 cases of OSCC from the departmental archives from 2006 to 2014. Subjects and Methods: Grading of each case was done by Bryne's grading system. The preoperative complete blood counts, relevant case history, and clinical data of the patients involved in the study were collected from the institutional medical records. The NLR was calculated by dividing the serum neutrophil count by the serum lymphocyte count. Statistical Analysis Used: The median NLR was compared between the controls and OSCC cases using Wilcoxon-signed rank test, and the Kaplan-Meier survival analysis was carried out to predict the survival and recurrence status of OSCC. Results: Higher NLR was seen in lymph node and margin-involved cases and also in patients who had tumor recurrence. Kaplan-Meier survival analysis showed that the mean survival dropped from 26 to 4.5 months when NLR ≥5 (P = 0.052). Conclusion: Neutrophil-to-lymphocyte ratio can be used as a prognosticator of survival, recurrence, lymph node status, and margin status in OSCC.

The promising impact of molecular profiling on treatment strategies in oral cancers

Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality. Although OSCC may develop from easily accessible oral preneoplastic lesions (OPLs), no intervention has been reported so far that reduces the rate of malignant transformation. A comprehensive molecular characterization of oral carcinogenesis may help refining treatment strategies both in patients with OPLs and OSCC. Herein, we review main molecular alterations occurring at different steps during oral carcinogenesis and show how molecularly-based medicine and surgery may impact the outcome of OSCC in the future.

Kif4A mediate the accumulation and reeducation of THP-1 derived macrophages via regulation of CCL2-CCR2 expression in crosstalking with OSCC

Crosstalk between tumor infiltrating macrophages and tumor cells is thought to play an indispensable role in oral squamous cell carcinomas (OSCC) by induction and maintenance of tolerance microenvironment. High infiltration of M2 macrophages and increasing expression of Kinesin family member 4A (Kif4A) in primary OSCC have been proved to correlate with greater tumoral size and poor clinical outcome. However, linkage between Kif4A and infiltrating macrophages in tumorigenesis and progression remains unclear. In the present study, we show that, the interaction between THP-1derived macrophage and OSCC cell line Cal-27 may up-regulate the Kif4A expression in both of them. Additionally, elevated soluble CCL2 in medium and more expression of CCR2 on macrophage were observed during the crosstalk. SiRNA of Kif4A and neutralizing antibody of CCL2 were utilized to identify that; increasing Kif4A can promote the recruitment of macrophages towards Cal-27 and educate them to M2 polarized macrophages via regulating CCL2/CCR2. In combination, the results of the present study may provide interesting clues to understanding the Kif4A-CCL2/CCR2-macrophage axis as a novel therapeutic target to improve the clinical outcome of OSCC.

Analysis of clinicopathological characteristics associated with the outcome of oral squamous cell carcinoma and the establishment of tissue microarrays.

The aim of this study was to evaluate clinicopathological risk factors associated with the fatal outcome of oral squamous cell carcinoma (OSCC) in a large cohort of Chinese patients, and to construct tissue microarrays (TMAs) using this cohort. Univariate and multiple logistic regression analyses were performed to evaluate the predictors of poor prognosis in a cohort of 232 patients with OSCC, after which the patient tumor tissues were used to construct TMAs. Univariate logistic regression analysis indicated that a poor outcome of OSCC was associated with the male gender, a history of smoking, the tumor-node-metastasis stage and lymph node metastasis. Multiple logistic regression analysis demonstrated that an increased risk of mortality in patients with OSCC was significantly and independently associated with lymph node metastasis (odds ratio, 3.421; 95% confidence interval, 1.609–7.273). Therefore, the results of the present study suggested that lymph node metastasis is an independent risk factor associated with a poor prognosis of OSCC patients. TMAs of OSCC were successfully constructed, and are the first TMAs to be reported in mainland Chinese patients.