Increased SEC14L2 expression is associated with clinicopathological features and worse prognosis in oral squamous cell carcinoma.

Abnormal expression of SEC14L2 has been implicated in many human cancers. However, the role of SEC14L2 in oral squamous cell carcinoma (OSCC) remains unclear. Therefore, this study aimed to evaluate the expression and prognostic roles of SEC14L2 in OSCC. OSCC tumors and adjacent non-tumors were collected from OSCC patients and used for SEC14L2 mRNA expression by quantitative reverse transcription PCR (RT-qPCR). Additionally, the expression of SEC14L2 was further analyzed using The Cancer Genome Atlas-Head Neck Squamous Cell Carcinoma (TCGA-HNSCC) dataset to identify its relationship with HNSCC clinical characteristics. The Kaplan-Meier plot was used to assess survival rates, and the Tumor Immune Estimation Resource (TIMER) database was used to examine the correlation between SEC14L2 expression and tumor immune cell infiltration. In silico tools also looked at SEC14L2 involvement in cancer pathways through its protein network. The mRNA and protein levels of SEC14L2 are notably higher in both OSCC and HNSCC tissues compared to adjacent normal tissues. Upregulation of SEC14L2 was associated with advanced tumor stages, grades, metastasis, HPV-negative, and TP53 mutations in cancer patients. In addition, the high expression of SEC14L2 was negatively correlated with the poor survival of cancer patients and the infiltration of diverse immune cells in cancer patients. According to the findings of this investigation, SEC14L2 is significantly elevated in OSCC/HNSCC patients and associated with a worse prognosis. More investigation and clinical studies are required to completely understand the therapeutic potential of SEC14L2 in HNSCC and convert these findings into better patient outcomes.

Triggering receptor expressed in myeloid cells 1 (TREM1) as a potential prognostic biomarker and association with immune infiltration in oral squamous cell carcinoma.

OBJECTIVE: The objective of this study is to investigate the significance and impact of Triggering Receptor Expression on Myeloid Cells-1 (TREM-1) in the context of oral squamous cell carcinoma (OSCC). METHODS: This study involved 51 OSCC patients, 21 oral epithelial dysplasia patients (OED), and the TCGA-HNSCC dataset. TREM1 expression was analyzed using quantitative reverse transcription PCR (RT-qPCR), and Western blot. Furthermore, we assessed TREM1 expression for clinicopathological, prognosis, and immune infiltration correlations utilizing publicly available TCGA-HNSCC datasets through UALCAN, Protein Atlas, Kaplan-Meier plot, TIMER2.0, and TISIDB. We also conducted bioinformatic analyses for functional enrichment employing publicly accessible datasets. RESULTS: TREM1 was significantly upregulated in OSCC and OED when compared to normal tissues, confirmed through multiple methods. Analysis of clinicopathological features showed associations with disease stage, grade, nodal metastasis, HPV status, and TP53 mutation. High TREM1 expression correlated with poorer patient survival. TREM1 was linked to immune cell infiltration and immune-related pathways. CONCLUSION: TREM1 is significantly upregulated in OSCC and is associated with poor clinicopathological features and survival. It may hold promise as a therapeutic target and prognostic marker in OSCC. Further research is needed to understand its functional role in OSCC.

Alteration of SERPINH1 is associated with elevated expression in head and neck squamous cell carcinomas and its clinicopathological significance.

BACKGROUND/PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer-related death worldwide and contributes significantly to the burden of disease in South Asia, partially due to the lack of effective screening strategies. Identifying essential biomarkers is crucial for improved prognosis and treatment. This study investigates the potential of SERPINH1 as a prognostic marker in HNSCC, highlighting its significance amidst the molecular complexity. METHODS: The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumors and 44 normal tissues, was analyzed using cBioportal, UALCAN, and Protein atlas tools. Expression patterns, survival outcomes, and clinical correlations of SERPINH1 were evaluated. In-depth analyses involved oral squamous cell carcinoma (OSCC) patient samples, protein expression, and functional exploration using various in-silico tools. RESULTS: SERPINH1 exhibited significant alteration and upregulation in HNSCC and OSCC, indicating its pan-cancer potential. Immunohistochemistry confirmed its overexpression in primary HNSCC tumors. Association analyses linked altered SERPINH1 levels with tumor stage, grade, metastasis, human papillomavirus (HPV) status, and patient prognosis. Functional analyses unveiled SERPINH1's involvement in critical cellular pathways and interactions with various proteins. CONCLUSION: The significant alteration of SERPINH1 associated with upregulated expression in HNSCC and OSCC positions it as a promising diagnostic and prognostic marker. Further investigations are warranted to elucidate the underlying molecular mechanisms, paving the way for targeted therapeutic interventions and continued exploration of various malignancies.

Aberrated PSMA1 expression associated with clinicopathological features and prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a globally prevalent cancer with significant mortality rates. OSCC a predominant subtype of head and neck squamous cell carcinoma (HNSCC), poses a substantial health burden. Despite advancements in diagnosis and therapy, OSCC prognosis remains poor. The 26S proteasome, a cellular protein degradation complex, is associated with cancer, including PSMA1, a proteasomal subunit, which is upregulated in various cancers. We analyzed PSMA1 expression using TCGA data, validated it in OSCC samples using real-time PCR, and explored its role through various databases. Tumor and adjacent normal tissues from OSCC patients were examined, and PSMA1 expression was analyzed. Survival analysis assessed the impact of PSMA1 on patient outcomes, while immune infiltration was examined using the TIMER database. GeneMANIA, STRING, and Metascape were utilized for gene interaction and pathway analysis. PSMA1 was significantly upregulated in OSCC and HNSCC. Its overexpression correlated with advanced clinicopathological features and poorer prognosis in HNSCC patients. PSMA1 expression is also related to immune cell infiltration. Gene interaction analysis revealed PSMA1 involvement in proteolysis regulation, suggesting its potential as a therapeutic target. PSMA1 upregulation in HNSCC association with adverse clinicopathological features and prognosis underscores its potential significance. Further research is warranted to elucidate its molecular mechanisms and therapeutic potential in OSCC management.

EXT2: a novel prognostic and predictive biomarker for head and neck squamous cell carcinoma.

OBJECTIVE: This study focused on EXT2, a member of the EXT family involved in heparan sulfate synthesis, to evaluate its potential as a prognostic and predictive biomarker in head-neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The present study used the cancer genome atlas head-neck squamous cell carcinoma (TCGA-HNSC) dataset-based UALCAN database to analyze the EXT2 expression and its clinicopathological features. In addition, we recruited 51 oral squamous cell carcinoma patients (OSCC), the most common HNSCC subtype, to validate the EXT2 mRNA expression analysis. In addition, we identified the role of EXT2 in prognosis using a Kaplan-Meier plot and immune signature using the tumor infiltration level. Furthermore, functional roles were analyzed using the EXT2 gene and protein networks. RESULTS: The expression of EXT2 mRNA was significantly upregulated in OSCC tumors, which is consistent with the UALCAN-based results. EXT2 protein was also significantly overexpressed in HNSCC samples and was correlated with clinicopathological features. High EXT2 expression is associated with poor survival outcomes in HNSCC patients. Functional analysis of EXT2 using in silico tools revealed its involvement in critical pathways, including Wnt signaling, proteoglycans in cancer, and cellular responses to fibroblast growth and inflammation. CONCLUSION: These findings highlight the potential of EXT2 as a prognostic and predictive biomarker of HNSCC.

Alteration in PNMA1 expression is associated with poor prognosis and tumor immune infiltration in head and neck squamous cell carcinoma.

Background: A significant percentage of the world is distressed due to the widespread and aggressive head and neck squamous cell carcinoma (HNSCC). The prognosis for people with HNSCC remains grim, despite progress in treatment techniques. This underscores the pressing demand for the discovery of novel biomarkers to enable early detection and improve prognostic categorization. Objective: The present study aims to identify the expression of the PNMA1 gene in HNSCC with clinicopathological characteristics, prognosis, and association of immune cells infiltration. Methods: The TCGA-HNSCC dataset first evaluated PNMA1 expression and its relationship to clinical aspects of HNSCC. Following that, oral squamous cell carcinoma (OSCC), a primary HNSCC type, is used to validate PNMA1 mRNA expression, via quantitative reverse transcription PCR (RT-qPCR). The Kaplan-Meier plot was used to assess survival rates, and the Tumour Immune Estimation Resource (TIMER) database was used to examine the relationship between PNMA1 and immune cells infiltration. Results: The expression of PNMA1 significantly increased in HNSCC and OSCC tumors. Significant correlations have been found between the increased PNMA1 expression and clinicopathological characteristics of HNSCC, such as tumor stage, grade, metastasis, HPV status and patient survival. PNMA1 expression also correlated with immune cell infiltration and immune regulator genes. Conclusion: In conclusion, the present study demonstrated that the PNMA1 expression significantly increased in HNSCC and was associated with HNSCC patient's prognosis. Hence, PNMA1 could serve as a novel prognostic biomarker and a promising therapeutic target for HNSCC.

DYNC1I1 acts as a promising prognostic biomarker and is correlated with immune infiltration in head and neck squamous cell carcinoma.

BACKGROUND/PURPOSE: Dynein Cytoplasmic 1 Intermediate Chain 1 (DYNC1I1) is a crucial cytoplasmic dynein binding component, its high expression levels are associated with malignant progression and poor survival in different types of cancer; however, the oncogenic role of DYNC1I1 in Head and neck squamous cell carcinomas (HNSCC) remains to be elucidated. In our present study, we aimed to explore the potential role of DYNC1I1 expression in the tumorigenesis of HNSCC and the shaping of the immune microenvironment. MATERIALS AND METHODS: The expression levels of DYNC1I1 were analyzed in The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset, and then real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate the DYNC1I1 expression in oral squamous cell carcinoma (OSCC) tumor samples, one of the major types of HNSCC. The functional pathway, tumor immune infiltration, and gene expression correlation for DYNC1I1 were performed using different bioinformatic tools. RESULTS: We found that the expression of DYNC1I1 was significantly increased in HNSCC and was a predictor of poor survival. The DYNC1I1 high expression has also been associated with an increased risk of HPV-negative HNSCC and decreased immune cell infiltration. Functional enrichment analysis identified that DYNC1I1 is involved in several important signaling pathways that contribute to the cancer cell's survival and proliferation. CONCLUSION: Our findings indicate that DYNC1I1 plays an important role in the tumorigenesis of HNSCC, and could be a promising prognostic biomarker for HNSCC diagnosis and treatment.

RFC3 serves as a novel prognostic biomarker and target for head and neck squamous cell carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer that originates from the squamous cells. The role of the replication factor C subunit 3 (RFC3) in HNSCC progression remains elusive. The aim of this study was to uncover RFC3 significance in HNSCC. METHODS: The Cancer Genome Atlas (TCGA-HNSCC) dataset was initially used to assess RFC3 expression and its association with HNSCC clinical features. Subsequently, quantitative reverse transcription PCR (RT-qPCR) confirmed RFC3 mRNA expression in oral squamous cell carcinoma (OSCC), a primary HNSCC type. Survival rates were evaluated using the Kaplan-Meier plot, while the Tumor Immune Estimation Resource (TIMER) database probed RFC3-immune cell interaction. Additionally, in silico tools were used to examine the RFC3 protein network and engagement in HNSCC pathways. RESULTS: RFC3 expression is significantly upregulated in HNSCC, including OSCC. Upregulated RFC3 expression was significantly correlated with the clinicopathological features of HNSCC, including tumor stage, grade, metastasis, and patient survival. RFC3 is also associated with immune cell infiltration. Functional analysis has highlighted its involvement in DNA replication, mismatch repair, and cell cycle pathways. Interestingly, RFC3 high expression is linked to well-known oncogenic signaling pathways, such as MYC/MYCN, HIPPO, and mTOR. CONCLUSIONS: In conclusion, RFC3 can be considered a novel prognostic biomarker for HNSCC, and further studies on its functional mechanisms may help to use RFC3 as a therapeutic target for HNSCC. CLINICAL RELEVANCE: The clinical relevance of this study lies in identifying RFC3 as a novel biomarker and prognostic indicator for HNSCC, offering insights that could impact future clinical approaches.

Prognostic and clinicopathological significance of MRC2 expression in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive types of cancers worldwide, with metastasis being the major cause of death. Recent research suggests that changes in the expression of MRC2 (mannose receptor, C-type 2) may play a role in the development and progression of various cancers; however, its expression pattern in HNSCC/ OSCC is unknown. This study aimed to elucidate the clinicopathological significance and prognostic role of MRC2 expression in HNSCC, including OSCC. MATERIALS AND METHODS: In the present study, we assessed the potential roles of MRC2 in expression, prognostic value, immune infiltration and functional enrichment analysis in HNSCC patients by using different bioinformatics databases. We then validated MRC2 gene expression in 30 OSCC and adjacent normal tissue samples using quantitative reverse transcription PCR (RT-qPCR). RESULTS: MRC2 mRNA and protein expression were significantly upregulated in OSCC and HNSCC patients compared to that in adjacent normal tissues. Upregulated MRC2 expression was associated with poor overall survival. Increased MRC2 expression has also been linked to an aggressive clinicopathological features including advanced stages, grade, metastasis and HPV status. Interestingly, our in silico results strongly suggest that the MRC2 gene and protein interaction networks are associated with HNSCC development. Moreover, the tumor infiltration level was significantly correlated with HPV-negative HNSCC patients. CONCLUSION: Our results suggest that MRC2 could be used as a novel prognostic marker and therapeutic target for HNSCC.

High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma.

BACKGROUND: Transforming growth factor ß regulator 4 (TBRG4) is a potential prognostic indicator in various cancers, especially squamous cell carcinomas, and is associated with disease amelioration and poor outcomes. The study aimed to assess the expression pattern of TBRG4 in patients with operable oral squamous cell carcinoma (OSCC) to understand its role in tumour progression using indicators of disease outcome like tumour stage, grade, nodal metastasis, and pattern of invasion. METHODS: TBRG4 expression was assessed by analyzing 51 cancer and adjacent non-cancerous tissues of OSCC patients using quantitative real-time PCR, and Western blot. TBRG4 expression was also analysed in The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset using the UALCAN tool (http://ualcan.path.uab.edu/). The relationship between TBRG4 expression and the patient's prognosis was analysed using Kaplan-Meier plotter. RESULTS: Both mRNA and protein levels of TBRG4 were significantly increased in OSCC tissues. The TBGR4 expression was significantly associated with advanced stages (III and IV) and the worst pattern of invasion (WPOI-4 and 5). High TBRG4 expression was also significantly associated with reduced overall survival (p = 0.011). In addition, the analysis of TBRG4 gene expression and clinical data from TCGA, identified that TBRG4 was highly expressed in HPV negative OSCC patients and positively correlated with worst overall survival. CONCLUSION: The present study suggests that the high expression of TBRG4 might serve as a novel prognostic biomarker for HPV-negative OSCC, which can be validated by future additional investigations in larger cohorts along with functional studies.

Decreased expression of the m6A RNA methyltransferase METTL3 is associated with residual ridge resorption.

Objective: N6-methyladenosine (m6A) methylation and its regulators play crucial roles in the progression of osteoporosis (OP) by regulating the expression of osteoporosis-related genes. In this study, we have analyzed the expression of methyltransferase-like 3 (METTL3) and its target gene Runt-related transcription factor 2 (RUNX2) in patients with residual ridge resorption (RRR). Materials and methods: A total 50 number of participants were included in this comparative study (RRR - n25 and healthy control - n25). Total RNA was extracted from peripheral blood and converted into cDNA. METTL3 and RUNX2 expression levels were quantified using RT-qPCR with GAPDH as the reference gene. Bioinformatics tools were used to identify gene functions and pathways. Results: Real-time polymerase chain reaction (qPCR) revealed that METTL3 and RUNX2 expression was downregulated in the RRR group compared to that in healthy controls (P < 0.05). In silico functional analysis provided information regarding the role of METTL3 in various biological processes. Conclusion: Our findings suggest that METTL3 dysregulation contributes to RRR pathogenesis. Further large-scale samples and functional studies are required to identify their therapeutic potential.

Dysregulated m6A methylation modification is associated with human peri-implantitis - A pilot study.

BACKGROUND: N6-methyladenosine (m6A) RNA modification and its regulatory enzymes play important roles in the modulation of inflammation by regulating inflammation-related gene expression. Dysregulation of m6A has been associated with inflammatory diseases, including periodontitis. This study aimed to investigate the potential role of m6A modification and its master regulatory enzyme METTL3 in patients with peri­implantitis. MATERIALS AND METHODS: Peri-implant soft tissues from 20 subjects (10 healthy controls and 10 patients with peri­implantitis) were enrolled in this study. Quantitative reverse transcription PCR (RT-qPCR) was used to detect METTL3 gene expression and western blotting was used to detect METTL3 protein expression. The m6A mRNA levels were measured using an m6A-RNA methylation quantification kit. Protein-protein interaction networks and in silico functional analyses were conducted using various bioinformatics tools. RESULTS: m6A mRNA levels significantly increased in the peri­implantitis group. Higher METTL3 mRNA and protein levels were observed in the peri­implantitis group. High METTL3 expression might influence elevated levels of m6A RNA methylation. In addition, in silico functional analysis indicated that the METTL3 gene and protein were associated with inflammatory pathways. CONCLUSIONS: Our data provide evidence, for the first time, that dysregulation of m6A modification is associated with peri­implantitis and may represent a strong risk factor for this inflammatory disease.

The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases.

Periodontitis is a chronic oral inflammatory disease that is caused by dental plaque pathogens. Periodontal disease development and evolution are based on the host immune system, humoral and cellular immunity, the integrity of the tissues, and certain endocrine and nutritional factors. Mitochondria are significantly involved in periodontal infections and inflammation, which play a role in the inflammatory response in a variety of ways. In general, oxidative stress causes a stressful environment that subsequently leads to tissue damage and chronic inflammation. Several mutations and alterations in mitochondrial DNA lead the disease to an aggressive condition, by causing dysregulated mitochondrial function. Such mutations are significantly associated with various diseases. Numerous studies indicate chronic periodontitis patients have a decreased level of mitochondrial membrane potential, as well as adenosine triphosphate, and an increased level of reactive oxygen species production, which causes cell death in the periodontium and affects tissue growth. Further studies into the association between mitochondria and periodontitis might be helpful for the treatment and prevention of the diseases.

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype-Phenotype Analysis.

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the BTD gene are reported worldwide. Mutations in the BTD gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the BTD gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.

Exploring the Expression of BCAS3 in Head and Neck Squamous Cell Carcinoma and Its Association With Prognosis.

Background Head and neck squamous cell carcinoma (HNSCC) is a prominent global cancer that manifests across diverse sites such as the oral cavity, oropharynx, and larynx. Human papillomavirus (HPV) infection and genetic alterations contribute to HNSCC development. Objective To investigate the complex role of breast carcinoma amplified sequence (BCAS3) in HNSCC pathogenesis. Methods We used multiple databases to analyze BCAS3 expression in HNSCC using The Cancer Genome Atlas-Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset and validated it in oral squamous cell carcinoma (OSCC) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The BCAS3 gene and protein networks were analyzed to identify their functional pathways. Results The results revealed significant overexpression of BCAS3 was observed in HNSCC and OSCC tumors. Our study explores BCAS3's correlation with clinicopathological features and patient prognosis, suggesting its involvement in tumor aggressiveness. Notably, BCAS3 expression in HPV-positive and HPV-negative HNSCC samples emphasizes the intricate viral interactions. Kaplan-Meier plots demonstrate BCAS3's impact on patient survival. Furthermore, BCAS3's association between tumor immune infiltration and autophagy was uncovered. Conclusion Our study contributes to the understanding of BCAS3's role in HNSCC and suggests its potential as a therapeutic target and diagnostic marker for these malignancies.

Increased Expression of LIPC Is Associated With the Clinicopathological Features and Development of Head and Neck Squamous Cell Carcinoma.

Introduction Lipase C hepatic type (LIPC) is a member of the lipase family and plays a role in tumor development. However, its specific role in head and neck squamous cell carcinoma (HNSCC) is not well understood. Objective This study aims to investigate LIPC gene expression in HNSCC and elucidate its potential role in the context of the disease. Methods LIPC expression was analyzed using the Cancer Genome Atlas-HNSCC (TCGA-HNSCC) dataset. Real-time polymerase chain reaction (qPCR) was used to validate LIPC expression in oral squamous cell carcinoma (OSCC) tissue samples, which is the most common type of HNSCC. The LIPC was assessed to find out if there is a link with HNSCC clinicopathological features, prognosis, and tumor infiltration. Functional pathways associated with the LIPC network were also examined. Results LIPC expression was found to be elevated in both HNSCC and OSCC tissues. The heightened expression of LIPC correlated with various clinicopathological features and influenced the prognosis of HNSCC patients. The LIPC gene demonstrated connections with several oncogenic genes and proteins, participating in lipid catabolic processes and other pathways. These findings suggest that LIPC expression may play a role in the pathogenesis of HNSCC. Conclusion Our study affirms that LIPC expression is linked to the development of HNSCC, suggesting its potential utility as a biomarker or therapeutic target for the disease. However, further functional studies are imperative to validate and expand upon these findings.