Triggering Receptor Expression on Myeloid Cells-1 (TREM1) Promoter Hypomethylation and Its Overexpression Associated With Poor Survival of Cancer Patients: A Pan-Cancer Analysis.

Background Triggering receptor expression on myeloid cells-1 (TREM1) belongs to the immunoglobulin superfamily and is implicated in various conditions, including infectious and non-infectious diseases, autoimmune disorders, and cancer. Notably, TREM1 is significantly dysregulated in numerous cancer types. However, the underlying mechanism driving TREM1 mRNA expression in cancers remains unclear.  Objective This study aims to analyze the promoter methylation level of TREM1 and its overexpression with cancer. Methods  This study utilized The Cancer Genome Atlas (TCGA) cohort to analyze the methylation and expression levels of TREM1 in cancers. The University of ALabama at Birmingham CANcer (UALCAN) database facilitated data analysis from the TCGA dataset. Additionally, survival analysis was conducted using the TCGA dataset via Kaplan-Meier (KM) plots to identify significant associations with prognosis. Results Promoter methylation analysis revealed that TREM1 is hypomethylated in cancers, resulting in significantly overexpressed mRNA across various cancer types. This methylation and expression showed a negative correlation. Furthermore, high TREM1 mRNA expression was linked to poor prognosis in several cancers. Conclusion TREM1 gene expression negatively correlates with promotor DNA methylation and is associated with poor survival. It may serve as a prognostic marker and biomarker for various cancers. Future research should focus on further validation and antitumor immunity to elucidate its oncogenic role in cancers.

Biallelic loss-of-function variations in BTD cause profound biotinidase deficiency in an Indian patient.

BACKGROUND: Biotinidase deficiency (BD) is a rare, autosomal recessive metabolic disorder characterized by neurocutaneous symptoms. This study investigates a case of profound BD in an Indian infant and the underlying genetic basis. METHODS: A 10-month-old male presenting with seizures, hypotonia, ataxia, visual impairments, and developmental delay underwent biochemical and genetic analysis. Biotinidase activity was measured using an ELISA kit. Sanger sequencing of the biotinidase (BTD) gene was performed to identify genetic variations. In silico analysis was employed to assess the potential impact of the identified variants. RESULTS: The infant biotinidase activity was undetectable and its suggest profound biotinidase deficiency. Novel biallelic loss-of-function variations (c.903G > A and c.946 C > T) in the BTD gene were identified, leading to premature stop codons and truncated, non-functional protein fragments. CONCLUSION: This case expands our knowledge of BD genetic diversity and underscores the critical role of early diagnosis and newborn screening programs in managing this treatable condition.

Overexpression of insulin-like growth factor-2 mRNA-binding protein 1 is associated with periodontal disease.

Objective: To investigate the potential role of a novel m6A RNA regulator, Insulin-like Growth Factor-2 mRNA-binding protein 1 (IGF2BP1), in periodontal disease pathogenesis. Materials and methods: Gingival tissue samples from 60 periodontitis patients and 60 healthy individuals were analyzed for IGF2BP1 mRNA and protein expression via real-time quantitative PCR (RT-qPCR) and Western blotting. Additionally, Porphyromonas gingivalis Lipopolysaccharide (Pg-LPS) -induced human gingival fibroblasts (HGFs) were evaluated for IGF2BP1 and proinflammatory cytokine expression. In silico functional analysis further explored potential molecular mechanisms. Results: IGF2BP1 mRNA and protein levels were significantly higher in the periodontitis group compared to the healthy group. Functional analysis implicated IGF2BP1 in regulating the IL-17 signaling pathway, a key player in inflammation. Pg-LPS treatment upregulated IGF2BP1 and proinflammatory cytokines in HGFs, supporting this finding. Conclusion: Our study suggests that IGF2BP1 overexpression contributes to periodontitis pathogenesis, potentially through IL-17 signaling. Further research is needed to elucidate the precise molecular mechanisms and explore IGF2BP1 as a potential therapeutic target or biomarker for this common oral disease.

The novel m6A writer methyltransferase 5 is a promising prognostic biomarker and associated with immune cell infiltration in oral squamous cell carcinoma.

BACKGROUND: Emerging research has identified the N6-methyladenosine (m6A) modification and its regulatory enzymes, including methyltransferase 5 (METTL5), as critical players in cancer biology. However, the role of METTL5 in oral squamous cell carcinoma (OSCC) remains poorly understood. MATERIALS AND METHODS: We conducted a comprehensive study to investigate the expression and implications of METTL5 in OSCC. We recruited 76 OSCC patients to analyze METTL5 mRNA and protein expression using RT-qPCR and western blot. Additionally, we analyzed METTL5 expression and its correlation with clinical features, patient prognosis, immune cell infiltration, and biological pathways using the TCGA-HNSCC dataset, which primarily consists of OSCC samples. RESULTS: Our findings revealed significant overexpression of METTL5 in OSCC tissues compared to normal tissues. The high expression of METTL5 is associated with advanced cancer stages, higher tumor grades, nodal metastasis, and poorer patient outcomes, indicating its involvement in cancer progression. In silico functional analysis revealed that METTL5 plays a role in multiple biological pathways, highlighting its importance in cancer biology. Moreover, METTL5 has complex relationships with immune regulatory genes, suggesting its potential role in shaping the tumor immune microenvironment. CONCLUSION: METTL5 is a promising candidate for the prognosis and therapeutic intervention of OSCC. Its overexpression in cancer tissues, association with clinical features, and intricate links to immune regulatory networks underscore its significance in this malignancy. This study contributes to a deeper understanding of the complex factors influencing OSCC, and provides a foundation for future research and potential clinical applications.

Aberrant expression of VASP serves as a potential prognostic biomarker and therapeutic target for oral squamous cell carcinoma.

OBJECTIVE: To address the molecular markers linked to the development and progression of oral squamous cell carcinoma (OSCC), we sought to analyze the expression of vasodilator-stimulated phosphoproteins (VASP) in OSCC samples. STUDY DESIGN: This study used 51 OSCC patients and The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset to analyze VASP expression. The association between VASP mRNA expression and HNSCC clinicopathological features, tumor infiltration, functional roles, and gene co-expression of VASP also were evaluated. RESULTS: Our study observed increased VASP mRNA expression in OSCC tumor tissues compared to normal tissues, supported by TCGA-HNSC dataset analysis. Elevated VASP levels correlated with advanced tumor stage, higher grade, nodal metastasis, and poor survival, indicating its potential as a prognostic marker. Protein analysis and immunohistochemistry confirmed these findings, and in silico analysis revealed VASP involvement in key cancer-related processes and its correlation with IL8, RAP1A expression, and tumor infiltration levels. CONCLUSIONS: In conclusion, VASP emerges as a promising diagnostic and prognostic marker for OSCC within HNSCC, emphasizing the importance of exploring its regulatory mechanisms and therapeutic applications. The revealed pathways present avenues for targeted treatment in OSCC. Despite limitations, this study provides valuable insights with potential implications for improving patient outcomes.

Waterpipe smoke condensate induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by FOXD1 expression.

BACKGROUND/PURPOSE: Smoking is a major contributor to global oral cancer cases, necessitating urgent intervention. FOXD1, involved in developmental processes and various cancers, shows promise as a prognostic marker in oral squamous cell carcinoma (OSCC). This study investigates the impact of waterpipe smoke condensate (WPSC) on OSCC, focusing on FOXD1 role in inducing epithelial-mesenchymal transition (EMT) and metastasis. METHODS: The study involved using OSCC cells treated with WPSC to evaluate their proliferation, colony formation, gene expression, and protein levels. The researchers also explored the clinical relevance of their findings using online databases to analyze FOXD1 expression in cancer tissues and its correlation with clinicopathological features and patient survival. Additionally, in silico tools were employed for functional analysis, pathway enrichment, and network exploration. RESULTS: The study found that WPSC increased the expression of FOXD1 in OSCC cells, which led to increased cell growth. The study also showed that FOXD1 plays a critical role in the EMT process induced by WPSC, as evidenced by changes in the expression of EMT-related genes and proteins. Clinical analysis revealed that FOXD1 was significantly associated with more aggressive tumor features and poorer prognosis in cancer patients. CONCLUSION: The study highlights FOXD1 as a key player in OSCC pathogenesis and a potential prognostic marker and therapeutic target, particularly when influenced by WPSC exposure. Further research is needed to explore FOXD1 molecular mechanisms and clinical implications to enhance OSCC treatment strategies.

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.

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.

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.