Stage Oral Squamous Cell Carcinoma Research Articles

Expression of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma and Their Relationship With Clinicopathological Parameters: A Cross-Sectional Study.

Background Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. The tumor microenvironment (TME) is a dynamic ecosystem composed of components contributed by both the tumor and the host. The immune cells of TME, mainly CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs), suppress the proliferation of cancer cells andplay a crucial role in the progression of OSCC. The present study aims to analyze the immunohistochemical expression of CD4+ and CD8+ TILs in OSCC and to compare and correlate them with clinicopathological parameters. Methodology A total of 75 formalin-fixed paraffin-embedded samples of cases diagnosed with primary OSCC wereimmunostained withCD4+ and CD8+ antibodies and their expression was compared with the clinicopathological parameters. Results There was a significant positive correlation between CD4+ and CD8+ expression (r = 0.655, p = 0.001).Both CD4+ (r = -2.37, p = 0.041) and CD8+ (r = -0.348, p = 0.002) expressions negatively correlated with the TNM stage (r = -2.37, p = 0.041) of OSCC. CD8+ expression positively correlated with histopathological grade (r = 0.288, p = 0.012). Conclusions The study findings suggest that CD4+ cells are essential to maintain and sustain CD8+ TIL-mediated anti-tumor response. CD4+ and CD8+ TILs are key players in cell-mediated adaptive immunity and prevent tumor progression and metastasis. Strikingly, the higher grade of tumors despite heavy CD8+ infiltration may possibly be due to cancer immunoediting.

Margin to depth of invasion ratio as an indicator for stratifying close margins in early-stage oral squamous cell carcinoma

ObjectivesIn early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. MethodsPatients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. ResultsWe analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). ConclusionFor early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

VAV2 orchestrates the interplay between regenerative proliferation and ribogenesis in both keratinocytes and oral squamous cell carcinoma

VAV2 is an activator of RHO GTPases that promotes and maintains regenerative proliferation-like states in normal keratinocytes and oral squamous cell carcinoma (OSCC) cells. Here, we demonstrate that VAV2 also regulates ribosome biogenesis in those cells, a program associated with poor prognosis of human papilloma virus-negative (HPV−) OSCC patients. Mechanistically, VAV2 regulates this process in a catalysis-dependent manner using a conserved pathway comprising the RAC1 and RHOA GTPases, the PAK and ROCK family kinases, and the c-MYC and YAP/TAZ transcription factors. This pathway directly promotes RNA polymerase I activity and synthesis of 47S pre-rRNA precursors. This process is further consolidated by the upregulation of ribosome biogenesis factors and the acquisition of the YAP/TAZ-dependent undifferentiated cell state. Finally, we show that RNA polymerase I is a therapeutic Achilles’ heel for both keratinocytes and OSCC patient-derived cells endowed with high VAV2 catalytic activity. Collectively, these findings highlight the therapeutic potential of modulating VAV2 and the ribosome biogenesis pathways in both preneoplastic and late progression stages of OSCC.

MicroRNA-21 as a biomarker in terminal stage oral squamous cell carcinoma (OSCC) in the South Indian population

ObjectiveMicro RNA-21(miR-21) earlier identified as high amount in different types of cancer. They are non-coding sequences with limited no of nucleotides and play important role in regulation of genes. Predicting the miR-21 levels could act as biomarkers for Oral Squamous Cell Carcinoma (OSCC). OSCC include every cancer found in the oropharynx and oral cavity. The current study retrieved mature sequences of miRNA from database- NCBI and used to find miRNA from OSCC. Its coming among the list of most prevalent malignancy in world, especially in India. This paper primarily focuses on miR-21 expression analysis as a biomarker of oscc in the South Indian population. Materials and methodsmiR-21 secondary structure is predicted using Bioinformatics tools from OSCC. Sequence was extracted from NCBI 25 OSCC samples and adjacent normal tissues were collected, and RNA were extracted, quantified, and reverse transcribed after doing histopathological analysis in cancer tissues. Expression of miR-21 done using qRT-PCR from the cDNA obtained. Utilizing statistical software, the relationship between the expression of miR-21 and the clinicopathological characteristics of OSCC was examined. Level of expression of genes in both cancer cells and normal cells are also analysed using graphical method. ResultmiR-21 secondary structure is predicted by applying mature sequence of miRNA. The values obtained by statistical analysis showed expression of miR-21 is increased in oscc samples compared to normal cells. ConclusionThus miR-21 is a potential biomarker associated with OSCC. Study also elucidated positive correlation between miR-21 in oscc samples.

Controversies in the treatment of early-stage oral squamous cell carcinoma

The treatment of early-stage oral squamous cell carcinoma (OSCC) is still a controversial issue. Thanks to the 8th edition of TNM by AJCC there is a better distinction between the stages of OSCC. However, Stages I and II still share the same treatment protocol, even if the prognosis is radically different. A retrospective study has been conducted including 70 previously untreated patients with Stage I or II OSCC, treated with tumorectomy and selective neck dissection. The study focuses on the link between pT1/2 and various other factors, particularly histological grading, vascular and perineural invasion, local and cervical recurrence, surgical margins and overall survival. These data reveal significant differences between pT1 and pT2 in histological grade, perineural invasion, cervical recurrence, surgical margins, and overall survival, emphasizing the necessity of different treatment protocols for T1 and T2 OSCC. Distinct strategies should be proposed to treat Stage I and II OSCC, with Stage II patients possibly benefitting from more aggressive treatments: following these data, a wait-and-see strategy should only be considered in Stage I, while certain treatments at the cervical level — such as prophylactic neck dissection and sentinel node biopsy — should always be considered for Stage II tumors.

Salivary Interleukin-1 Levels in Oral Squamous Cell Carcinoma: A Case-Control Study.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a significant impact on global health. The identification of non-invasive biomarkers for early detection and monitoring of OSCC remains crucial. A total of 100 subjects, comprising 50 patients with histopathologically confirmed OSCC and 50 age- and sex-matched healthy controls, were enrolled in the study. Salivary samples were collected from all participants and analyzed using enzyme-linked immunosorbent assays (ELISA) to measure IL-1 levels. Clinical data, including demographic information, smoking habits, and alcohol consumption, were obtained from patient records. The mean salivary IL-1 level was significantly higher in OSCC patients compared to healthy controls (P < 0.001). Furthermore, subgroup analysis demonstrated that advanced stages of OSCC correlated with significantly elevated IL-1 levels when compared to early-stage OSCC (P < 0.05). Additionally, high salivary IL-1 levels were associated with a more aggressive tumor phenotype and poorer prognosis, as reflected by tumor size, lymph node metastasis, and overall survival (P < 0.01). This case-control study provides compelling evidence that salivary Interleukin-1 (IL-1) levels are significantly elevated in patients with OSCC.

Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma

PurposeNear-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC.MethodsData were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted.ResultsIn all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min.ConclusionICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.

Oral Cavity Cancer Tissues Differ in Isotopic Composition Depending on Location and Staging.

The aim of this paper was to characterise the isotopic composition of oral squamous cell carcinoma (OSCC) specimens of different areas of the oral cavity. Secondly, we assessed whether there was a correlation between clinical stages of OSCC and isotopic abundance. The IRMS procedure was performed on 124 samples derived from 31 patients with OSCC of 15 N and 13 C to assess the isotopic composition. From each individual, four samples from the tumour, two from the margins, and two samples of healthy oral mucous membranes were derived. The two samples from the tumour and two samples from the margin were additionally subjected to histopathological assessment. Then, statistical analysis was conducted. Tumour infiltration tissues of the lower lip were characterised by higher mean δ13C values compared to samples derived from cancers of the other oral cavity regions (-23.82 ± 1.21 vs. -22.67 ± 1.35); (p = 0.04). The mean percentage of nitrogen content in tumour tissues was statistically higher in patients with the most advanced cancers (11.89 ± 0.03%) versus the group of patients with II and III stage cancers (11.12 ± 0.02%); (p = 0.04). In patients at stage IV, the mean δ13C value in the cancer samples equalled -22.69 ± 1.42 and was lower than that in patients at less severe clinical stages (p = 0.04). Lower lip cancer tissues differed in the isotopic abundance of carbon in comparison with tissues derived from the group of combined samples from other locations. Values of δ13C observed in specimens derived from lower lip cancers were similar to those observed in healthy oral mucous membranes. Cancer tissues obtained from patients in the last stage of OSCC had a different isotopic composition in comparison with those obtained from earlier stages. To confirm these observations, further research on larger groups of patients is needed.

Cost-Effectiveness of [99mTc]Tilmanocept Relative to [99mTc]Sulfur Colloid for Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer

BackgroundSeveral studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [99mTc]tilmanocept versus [99mTc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [99mTc]tilmanocept versus [99mTc]sulfur colloid in early stage OCSCC.Patients and MethodsA decision model of disease and treatment as a function of SLNB was created. Patients with a negative SLNB entered a Markov model of the natural history of OCSCC parameterized with published data to simulate five states of health and iterated over a 30-year time horizon. Treatment costs and quality-adjusted life-years (QALYs) for each health state were included. The incremental cost-effectiveness ratio (ICER) was then estimated using $100,000 per additional QALY as the threshold for determining cost-effectiveness.ResultsThe base case cost-effectiveness analysis suggested [99mTc]tilmanocept was more effective than [99mTc]sulfur colloid by 0.12 QALYs (7.06 versus 6.94 QALYs). [99mTc]Tilmanocept was more costly, with a lifetime cost of $84,961 in comparison with $84,264 for sulfur colloid, however, the overall base case ICER was $5859 per additional QALY, well under the threshold for cost-effectiveness. Multiple one-way sensitivity analyses were performed, and demonstrated the model was robust to alternative parameter values.ConclusionOur analysis showed that while [99mTc]tilmanocept is more costly upfront, these costs are worth the additional QALYs gained by the use of [99mTc]tilmanocept.

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC.

Identification of Healthy Tissue from Malignant Tissue in Surgical Margin Using Raman Spectroscopy in Oral Cancer Surgeries.

Accurate identification of tissue types in surgical margins is essential for ensuring the complete removal of cancerous cells and minimizing the risk of recurrence. The objective of this study was to explore the clinical utility of Raman spectroscopy for the detection of oral squamous cell carcinoma (OSCC) in both tumor and healthy tissues obtained from surgical resection specimens during surgery. This study enrolled a total of 64 patients diagnosed with OSCC. Among the participants, approximately 50% of the cases were classified as the most advanced stage, referred to as T4. Raman experiments were conducted on cryopreserved tissue samples collected from patients diagnosed with OSCC. Prominent spectral regions containing key oral biomarkers were analyzed using the partial least squares-support vector machine (PLS-SVM) method, which is a powerful multivariate analysis technique for discriminant analysis. This approach effectively differentiated OSCC tissue from non-OSCC tissue, achieving a sensitivity of 95.7% and a specificity of 93.3% with 94.7% accuracy. In the current study, Raman analysis of fresh tissue samples showed that OSCC tissues contained significantly higher levels of nucleic acids, proteins, and several amino acids compared to the adjacent healthy tissues. In addition to differentiating between OSCC and non-OSCC tissues, we have also explored the potential of Raman spectroscopy in classifying different stages of OSCC. Specifically, we have investigated the classification of T1, T2, T3, and T4 stages based on their Raman spectra. These findings emphasize the importance of considering both stage and subsite factors in the application of Raman spectroscopy for OSCC analysis. Future work will focus on expanding our tissue sample collection to better comprehend how different subsites influence the Raman spectra of OSCC at various stages, aiming to improve diagnostic accuracy and aid in identifying tumor-free margins during surgical interventions.

Simultaneous Detection of Two Extracellular Vesicle Subpopulations in Saliva Assisting Tumor T Staging of Oral Squamous Cell Carcinoma.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma-A new protocol for staging and treatment.

Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC. In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs. Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398). SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.

Elastin remodeling: Does it play a role in priming the malignant phenotype of oral mucosa?

The extracellular matrix (ECM) is a dynamic tissue that provides nutrition and support to overlying epithelium. During tumorigenesis, the tumor microenvironment (TME) dysregulates the ECM. This is reflected by morphological changes seen in collagen and elastic fibers and is thought to facilitate metastasis. To study the degradation of elastic fibers in different grades of oral squamous cell carcinoma (OSCC) and in oral epithelial dysplasia (OED) using histochemistry and to correlate it to the TNM stage of OSCC. Tumor cores from 38 cases of OSCC (well-differentiated[15], moderately differentiated[14], and poorly differentiated[9]) and 15 incisional biopsies of OED were analyzed. Hematoxylin-eosin and Verhoeff's-Van Gieson (VVG) stains were used. The stained sections were assessed for morphological changes in elastic fibers. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 22 software. Fisher's exact, Kruskal-Wallis, one-way ANOVA, and Turkey post hoc tests were used to establish significance (P ≤ 0.05). Spearman's correlation test was used to correlate elastin fiber degradation with TNM stage of OSCC. All grades of OSCC showed absence of elastic fibers around the tumor islands. Elastic fiber degradation (fragmented and clumped type fibers) increased proportionately with the grade and TNM stage of OSCC. In OED, A significant reduction in the amount of elastic fibers with increasing grade was noted. A positive correlation was noted between elastin degradation and grade and stage of OSCC. Therefore, it may be implicated in tumor progression of OSCC.

Assessment of depth of invasion in oral squamous cell carcinoma of the tongue: a study protocol

Background:Oral Squamous Cell Carcinoma (OSCC) is the most common malignancy of oral cavity. It remains a leading cause of mortality and morbidity around the world. Overall OSCC represents more than 550,000 cases throughout the world yearly and the 6thleading cause of death. The mortality and rate of OSCC are higher in developing nations. About 25% patients with OSCC of tongue exist with occult metastasis at initial presentation. The utilization of TNM staging of OSCC to assess the clinical response to treatment and survival result is for many years. Prognosis of malignancy also depends on the histopathological grading of the OSCC. Histopathological assessment by measuring Depth of Invasion (DOI) enables us the insight about the extent of invasion by neoplastic cells. This observation will further be helpful for treatment management protocol particularly in OSCC of tongue. Hence, we aimed to assess the significance of DOI in the prognosis and clinicopathological features and survival of OSCC lesions in the current study.Methods:The surgically operated cases of OSCC of tongue from year 2009 to 2015 will be retrieved from the archival. Measurement of DOI will be carried out using Research microscope. The staging of the patients will be done according to the American Joint Committee of Cancer staging system. The present study will find DOI in tongue OSCC and its correlation with the clinicopathological features of OSCC of tongue and three years disease-specific survival.Conclusion:Measurement of the DOI ought to be included as a part of routine histological assessment. This likewise should be utilized for grading the tumor, which can further help in treatment management protocol.

Role of Salivary Chemerin in Oral Squamous Cell Carcinoma (OSCC) Patients with and without Chronic Periodontitis

Background: Chemerin is a multifunctional protein that plays a role in immunological function, chemotaxis, energy metabolism, and basic cell activities. Chemerin dysregulation contributes significantly to tumor angiogenesis and disease progression. The study aimed to assess salivary chemerin levels in Oral squamous cell carcinoma (OSCC) patients with/without chronic periodontitis, as well as, investigate the relationship between chemerin levels and OSCC stages. Methods: This case-control study was conducted at the Dental OPD of Ziauddin University Hospital and Liaquat National Hospital Karachi Pakistan from January 2020-2021. A total of n=60 participants, 15 each of OSCC with and without periodontitis and 15 controls of periodontitis alone and 15 healthy controls were included in the study. The salivary levels of chemerin were measured by ELISA. The mean salivary chemerin level was compared using Kruskal–Wallis’s test among the stages, sites and grades of OSCC. A p-value &lt;0.05 was considered statistically significant. Results: The mean age of study participants was estimated as 43.42±13.19 years (range: 20-60 years). The mean salivary chemerin levels in OSCC were highest in the late stages; 18.88±8.8 ng/ml in stage III and 17.63±5.09 ng/ml in stage IV. A statistically significant difference was observed in mean salivary chemerin levels concerning the stage of OCSS (p=0.025). Furthermore, periodontal status was statistically associated with the site of the tumor (p&lt;0.05). Conclusion: In OSCC and periodontitis, salivary chemerin levels were shown to be higher compared to healthy controls (p=0.025). Therefore, it can be utilized as a new therapeutic target for detecting tumorigenesis. Keywords: Chemerin; Oral Squamous Cell Carcinoma; Periodontitis; Periodontal Disease; Saliva; Salivary Chemerin Level.

Zinc-alpha 2 glycoprotein a diagnostic Biomarker for early stage oral Squamous Cell Carcinoma.

In this study, we investigated the expression of zinc alpha-2 glycoprotein in oral squamous cell carcinoma tissue samples. Additionally, ascertained its association to the oral cancer stage and subscale parameters (TNM). This observational study was conducted at Ziauddin University from January to December 2020. Using the Open-Epi software, the sample size of 120 oral squamous cell carcinomas was calculated at 95% confidence interval and a 5% margin of error. Ethical approval was taken from the Institutional Ethical Review Committee. Histologically diagnosed cases of oral squamous cell carcinoma were obtained from the Histopathology Department of Ziauddin University, Karachi. Study data was analyzed through SPSS version-20 and p-value ≤0.05 considered as significant. One-way ANOVA and Multiple linear regression were applied for analysis of data. In the study, none of the oral squamous cell carcinoma tissue samples from the later stages were stained for ZAG. However 71% (35/49) of the early stage OSCC samples showed positive IHC results for ZAG expression in the cytoplasm. One-way ANOVA indicates that high ZAG expression was significantly associated with smaller tumor size (p<0.001), lymph node involvement (p=0.002), early stages of OSCC (p<0.001) and less differentiated tumor (p=0.001). The site of the tumor was also significantly associated with ZAG staining (p<0.001). Zinc alpha-2 glycoprotein expressed in the early stages of oral cancer development so that effective treatment modalities can be planned as per the patient's status. This may also assist a clinician to achieve tumor-free surgical margins and monitor the post treatment outcomes.

Tissue mechanics modulate PCNP expression in oral squamous cell carcinomas with different differentiation.

PEST-containing nuclear protein (PCNP), a novel zinc finger protein, participates in cell cycle regulation. Previous studies have confirmed that PCNP plays a role in mediating cellular development and invasion in a variety of cancer types. However, the relationship between PCNP expression and the occurrence and development of oral squamous cell carcinoma (OSCC) requires further exploration. In this study, we used biological atomic force microscopy to examine the histomorphological and mechanical properties of OSCC to explore the relationship between PCNP expression and differentiation of OSCC. Seventy-seven OSCC samples with varying degrees of differentiation were selected for hematoxylin and eosin staining, immunohistochemistry, and cellular mechanical measurement. The expression of PCNP and the mechanical properties such as stiffness and roughness of the tissue interface in OSCC samples were investigated. The Kaplan-Meier survival curve was utilized to assess the relationship of PCNP expression with patient survival. The level of PCNP was significantly higher in well-differentiated OSCC than in moderately and poorly differentiated OSCC (P < 0.001). High expression of PCNP was specifically associated with higher tumor differentiation, lack of lymph node metastasis, and lower tumor node metastasis stage (all P < 0.05). Patients with high PCNP expression had a higher survival rate than those with low PCNP expression. The average variation of stiffness within a single tissue ranged from 347 kPa to 539 kPa. The mean surface roughness of highly, moderately, and poorly differentiated OSCC and paraneoplastic tissues were 795.53 ± 47.2 nm, 598.37 ± 45.76 nm, 410.16 ± 38.44 nm, and 1010.94 ± 119.07 nm, respectively. Pearson correlation coefficient demonstrated a positive correlation between PCNP expression and tissue stiffness of OSCC (R = 0.86, P < 0.001). The expression of PCNP was positively correlated with patient survival, tumor differentiation, and mechanical properties of tissue interfaces. PCNP is a potential biomarker for the early diagnosis and staging of OSCC. Furthermore, determination of the mechanical properties of the tissue interface could provide further useful information required for the detection and differentiation of OSCC.

Identification of novel stage-specific key biomarkers gene for early stage, advanced stage, and metastatic oral squamous cell carcinoma using systems biology approach

Abstract Background: The present study aimed to identify biomarker genes associated with disease progression from an early and advanced stage to metastatic oral squamous cell carcinoma (OSCC) and to explore their regulatory mechanism. Materials and Methods: Three microarray datasets, GSE85195, GSE78060, and GSE70604, were used for differential analysis using a limma package of R language. The thresholds for identifying differential expression analyses (DEGs) were an adjusted P value of 0.05 and a |log 2 fold change (FC)| &gt;1. The final annotated genes were extracted by comparing the differentially expressed genes to disease-specific genes in DisGeNET. Further, gene prioritization was performed for DEGs. After that, prioritized DEGs were used to analyze functional enrichment using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, the prioritized DEGs were also used to construct protein–protein interaction (PPI) network using STRING database and visualized by the Cytoscape, and further analyzed by molecular complex detection (MCODE) and CytoHubba plugins to obtain essential hub genes and modules. Subsequently, the Kaplan–Meier plot was constructed for the hub gene using a publicly available dataset to analyze overall survival (OS) and to assess whether candidate molecules are prognosticators. Results: The study identified 10 hub genes for all three stages of OSCC. Top 10 highest-scored early-stage genes are AURKA, CDCA3, CDC45, CENPN, CDC6, MAD2L1, KIF4A, CDT1, PLK1, and CDC20; for advance stage, KIF4A, MAD2L1, AURKA, DTL, ESPL1, ECT2, CDC45, CDC20, CENPN, and CDC6; for metastatic stage, MFAP5, IRF6, P4HA2, COL11A2, COL10A1, LOXL2, BMP1, COL5A2, COL5A1, and ADAMTS14. Hub genes were enriched in the biological process associated gene ontology term: Positive regulation of the apoptotic process, positive regulation of cell proliferation, negative regulation of the apoptotic process, and angiogenesis Wnt signaling pathway, FoxO signaling pathway, and pathways in cancer. Except for ESPL1 and COL11A2, all hub genes were highly elevated in OSCC compared with normal tissues. According to the survival analysis results, low expression levels of CNPEN and MFAP5 were significantly linked to worse OSCC patients out of the 23 hub genes studied. Conclusion: Several putative biomarker genes were associated with OSCC patients’ staging and OS. Therefore, they may have clinical use as diagnostic biomarkers and therapeutic targets.

Association of Oral Squamous Cell Carcinoma and Human Papilloma Virus Status in Chronic Periodontitis Patients: A Cross-sectional Study

Introduction: Apart from the alcohol and tobacco which are considered as an important cause for carcinogenesis, periodontal infections have also been considered equally important cause for it. Infections are increasingly considered as potential trigger for carcinogenesis apart from alcohol and tobacco. The role of the Human Papilloma Virus (HPV) in causing Oral Squamous Cell Carcinoma (OSCC), highlights the significance of the oral infections in the development of the OSCC. Aim: To detect the relationship between Chronic Periodontitis, HPV, and OSCC. Materials and Methods: This was a cross-sectional study conducted on 15 chronic generalised periodontitis patients with OSCC affecting alveoli and gingiva. DNA was extracted from the biopsy of the tissue sample for the detection of HPV by Polymerase chain reaction (PCR). The parameters assessed were the Clinical Attachment Loss (CAL), Tumor Node Metastsis (TNM ) staging of OSCC, HPV status and the presence of the periodontal marker bacteria. Chi-square test and spearman correlation were used to find association and correlation between the parameters. Results: A total of 15 cases of chronic generalised periodontitis patients with oral squamous cell carcinoma were included in the study (7 males and 8 female patients, with a mean age of 50.8 years). Of these, HPV was found in 4 patients only. On comparison between Chronic Generalised Periodontitis (CGP) and OSCC, a non-significant association and a negative correlation was found. Similar analysis was observed between CGP and HPV. When comparison was done between HPV and OSCC, non-significant association (p-value 0.774) and a negative correlation(r- value= -0. 169) was found. Conclusion: This study did not yield a significant association and correlation between these three parameters. Further prospective studies should be conducted which may help in the prevention of periodontitis and subsequently decreasing the incidences of OSCC.