LDL Receptor-Related Protein 1B Polymorphisms Associated with Increased Risk of Lymph Node Metastasis in Oral Cancer Group with Diabetes Mellitus.

Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC; p = 0.046) were significantly associated with tumor size compared with those with homozygous major alleles (AA). Similarly, compared to genotypes homologous for the main allele (GG), rs6742944 genotypes (GA + AA; p = 0.010) were more likely to develop lymph node metastases. The tongue and the rs6742944 genotypes (GA + AA) exhibited higher rates of advanced clinical stages (p = 0.024) and lymph node metastases (p = 0.007) when compared to homozygous alleles (GG). LRP1B genetic polymorphisms appear to be prognostic and diagnostic markers for OSCC and DM, as well as contributing to genetic profiling research for personalized medicine.

Assessing Circulating Tumour DNA (ctDNA) as a Biomarker for Anal Cancer Management: A Systematic Review.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

A Review of the Repair of DNA Double Strand Breaks in the Development of Oral Cancer.

We explore the possibility that defects in genes associated with the response and repair of DNA double strand breaks predispose oral potentially malignant disorders (OPMD) to undergo malignant transformation to oral squamous cell carcinoma (OSCC). Defects in the homologous recombination/Fanconi anemia (HR/FA), but not in the non-homologous end joining, causes the DNA repair pathway to appear to be consistent with features of familial conditions that are predisposed to OSCC (FA, Bloom's syndrome, Ataxia Telangiectasia); this is true for OSCC that occurs in young patients, sometimes with little/no exposure to classical risk factors. Even in Dyskeratosis Congenita, a disorder of the telomerase complex that is also predisposed to OSCC, attempts at maintaining telomere length involve a pathway with shared HR genes. Defects in the HR/FA pathway therefore appear to be pivotal in conditions that are predisposed to OSCC. There is also some evidence that abnormalities in the HR/FA pathway are associated with malignant transformation of sporadic cases OPMD and OSCC. We provide data showing overexpression of HR/FA genes in a cell-cycle-dependent manner in a series of OPMD-derived immortal keratinocyte cell lines compared to their mortal counterparts. The observations in this study argue strongly for an important role of the HA/FA DNA repair pathway in the development of OSCC.

ATP Citrate Lyase is a General Tumour Biomarker and Contributes to the Development of Cutaneous Squamous Cell Carcinoma.

ATP citrate lyase, the first rate-limiting enzyme in de novo lipogenesis, plays a crucial role in tumour progression. This study explores ATP citrate lyase's potential as a tumour biomarker and its role in cutaneous squamous cell carcinoma. ATP citrate lyase expression patterns were analysed using TCGA and TIMER databases, and patient skin specimens were collected for immunohistochemistry to determine ATP citrate lyase levels. Cell proliferation, cell cycle, apoptosis, and c-Myc expression were assessed in A431 and SCL-1 cells. Stable cell lines with reduced ATP citrate lyase expression were obtained and subcutaneously implanted into nude mice to evaluate in vivo tumour growth. Ki67, c-Myc expression and TUNEL staining were analysed in subcutaneous tumours. ATP citrate lyase exhibited upregulation in various tumours, and showed significant associations with prognosis and immune infiltrate. Moreover, ATP citrate lyase was highly expressed in cutaneous squamous cell carcinoma. After ATP citrate lyase silencing, cutaneous squamous cell carcinoma cell growth decelerated, the cell cycle halted, cell apoptosis increased, and c-Myc expression decreased. Animal experiments revealed that, following ATP citrate lyase knockdown, tumour tissue growth slowed down, and there was a reduction in Ki-67 and c-Myc expression, accompanied by enhanced TUNEL staining. In conclusion, ATP citrate lyase may serve as a tumour biomarker. It is highly expressed in cutaneous squamous cell carcinoma and may serve as a therapeutic target.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).

The complex evolution of genetic alterations in cancer that occurs in vivo is a selective process involving numerous factors and mechanisms. Chemotherapeutic agents that prevent the growth and spread of cancer cells induce selective pressure, leading to rapid artificial selection of resistant subclones. This rapid evolution is possible because antineoplastic drugs promote alterations in tumor­cell metabolism, thus creating a bottleneck event. The few resistant cells that survive in this new environment obtain differential reproductive success that enables them to pass down the newly selected resistant gene pool. The present review aims to summarize key findings of tumor evolution, epithelial­mesenchymal transition and resistance to cetuximab therapy in head and neck squamous cell carcinoma.

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

Expression of lncRNA LINC00943 in lung squamous cell carcinoma and its relationship with tumor progression.

BACKGROUND: Molecular biology has been applied to the diagnosis, prognosis and treatment of various diseases, and long noncoding RNA LINC00943 (lncRNA LINC00943; LINC00943) plays an important role in a variety of cancers. Therefore, this study explored the prognostic role of LINC00943 in lung squamous cell carcinoma (LUSC) and understood its impact on the development of LUSC. METHODS: There are 89 LUSC patients were involved in current assay. By detecting the expression of LINC00943 and miR-196b-5p in tissues and cells, LINC00943 and its correlation with the characteristics of clinical data were analyzed. The biological function of LINC00943 was studied by Transwell migration and invasion assays. In addition, Pearson correlation coefficient and luciferase activity experiments were chosen to characterize the relationship between LINC00943 and miR-196b-5p and explore the mechanism of LINC00943. RESULTS: Compared with normal controls, LINC00943 expression in LUSC tissues and cells was significantly reduced, miR-196b-5p was markedly increased, there was a negative correlation between LINC00943 and miR-196b-5p. According to the in vitro cell experiments, migration and invasion of LUSC cells were suppressed by overexpression of LINC00943. Besides, LINC00943 was demonstrated to have prognostic power and targeting miR-196b-5p was involved in the progression of LUSC. CONCLUSIONS: Overexpression of LINC00943 was molecular sponge for miR-196b-5p that controlled the deterioration of LUSC, which had great potential as a prognostic biomarker for LUSC.

HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12.

Transcriptional factor HOXB9, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the HOXB9 gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the HOXB9 gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12. HOXB9 could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene, MMP12.

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer-A Validation Study.

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic-therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma.

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment ("sham"). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p<0.05) in SCC-VII-Luc cells at acoustic pressures 0.25 MPa to 0.9 MPa, while no significant silencing effect was seen at lower pressure (0.125 MPa). In vivo, EGFR siRNA LPX + UTMC reduced tumor EGFR expression by ~30% and significantly inhibited tumor growth by day 9 (~40% decrease in tumor volume vs. NC siRNA LPX + UTMC, p<0.05). Conclusions: Luc siRNA LPXs + UTMC achieved functional delivery of Luc siRNA to SCC-VII-Luc cells in vitro. EGFR siRNA LPX + UTMC inhibited tumor growth and suppressed EGFR expression in vivo, suggesting that this platform holds promise for non-invasive, image-guided targeted delivery of therapeutic siRNA for cancer treatment.

Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study.

BACKGROUND: Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T-cell infiltration via PD-L1, which lead to enhanced antitumor immunity and may target for immune-checkpoint inhibitors (ICIs) therapy. METHODS: This retrospective study analyzed the results of immunohistochemical staining for PD-L1 and CD8+ T-cell infiltration in 10 patients and whole-exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. RESULTS: Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.

Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated m6A modification.

BACKGROUND: Inhibin A and N6-methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6-methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene "Inhibin A" that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6-methyladenosine methyltransferase KIAA1429-mediated N6-methyladenosine methylation modification. METHODS: Bioinformatics analysis and quantitative real-time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit-8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation-qPCR, quantitative real-time polymerase chain reaction, and Western blotting experiments. RESULTS: Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6-methyladenosine level of Inhibin A in oral squamous cell carcinoma. CONCLUSIONS: Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated N6-methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.

In vitro antimetastatic potential of pseudolaric acid B in HSC-3 human tongue squamous carcinoma cell line.

OBJECTIVE: Pseudolaric acid B (PAB) is a novel diterpenoid derived from the traditional Chinese medicinal herb Cortex pseudolaricis that exerts anticancer, anti-inflammatory, and immunomodulatory properties. While the anticancer potential of PAB has been studied, its effects on metastasis have not been well-studied. This study aims to determine the inhibitory effects of PAB on HSC-3 human tongue squamous cell carcinoma (TSCC) cell line. DESIGN: Cell viability and soft agar colony formation assays were conducted to assess cellular proliferation and in vitro tumorigenic capacity of TSCC cells, respectively. Additionally, wound healing, transwell migration, and invasion assays were conducted to monitor the aggressive behavior of TSCC cells. Furthermore, Western blotting analysis was conducted to reveal the signaling pathways involved in the modulation of epithelial-mesenchymal transition (EMT). RESULTS: The migratory and invasive capacities of HSC-3 cells were suppressed by PAB irrespective of their proliferation states. PAB's effects on EMT involved upregulation of E-cadherin expression and downregulation of Twist; these were concomitantly accompanied by downregulated phosphorylation of epidermal growth factor receptor (EGFR). CONCLUSIONS: PAB suppresses human TSCC in vitro by regulating Twist/E-cadherin through the EGFR signaling pathway. PAB may have potential as a candidate antimetastatic drug for TSCC treatment.

Exploring the Role and Prognostic Value of TMEM208 in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the world's eight most common malignancies and a severe hazard to human health. Transmembrane protein 208 (TMEM208) has been reported to be associated with autophagy,which is strongly tied to the onset and development of numerous illnesses, including cancer. For this reason, we investigated the expression and prognostic significance of TMEM208 in HNSCC. METHODS: To explore the role and molecular mechanism of this gene in HNSCC, we performed a comprehensive analysis of the TMEM208 gene, including gene expression analysis, prognostic analysis, and immune infiltration analysis using the UALCAN, HPA, CVCDAP, DAVID, TIMER, CIBERSORTx, TISIDB, and cBioPortal online databases. It was further validated by in vitro cell culture. RESULTS: Analysis of TCGA data showed that TMEM208 was highly expressed in HNSCC (P < 0.01) and significantly correlated with several clinicopathologic features, and in vitro cellular assays demonstrated that TMEM208 was highly expressed in multiple squamous carcinoma cell lines. Survival analysis showed that high expression of TMEM208 decreased OS (P=0.0088), PFI (P=0.0062), and DSS (P=0.0036) in HNSCC patients. cox regression analysis indicated that high expression of TMEM208 was an independent risk factor for OS in HNSCC patients (P<0.05). In addition, functional enrichment analysis showed that TMEM208 was closely associated with translation, ribosomal and mitochondrial functions, and GSVA analysis showed that TMEM208 was negatively correlated with a variety of immune cell differentiation in HNSCC, with a statistically significant difference. Immunocorrelation analysis showed that TMEM208 could affect immune cell infiltration in HNSCC; in addition, TMEM208 correlated with CD24, CD276, LAG3, and HVEM. CONCLUSION: In conclusion, TMEM208 holds promise as a prognostic indicator for HNSCC and is closely related to ICI treatment.

Potential targets of diosgenin for the treatment of oral squamous cell carcinoma and their bioinformatics and transcriptional profiling analyses.

Diosgenin can inhibit the proliferation and cause apoptosis of various tumor cells, and its inhibitory effect on oral squamous cell carcinoma (OSCC) and its mechanism are still unclear. In this study, we predicted the targets of diosgenin for the treatment of OSCC through the database, then performed bioinformatics analysis of the targets, and further verified the effect of diosgenin on the activity of OSCC cell line HSC-3, the transcriptional profile of the targets and the molecular docking of the targets with diosgenin. The results revealed that there were 146 potential targets of diosgenin for OSCC treatment, which involved signaling pathways such as Ras, TNF, PI3K-AKT, HIF, NF-κB, and could regulate cellular activity through apoptosis, autophagy, proliferation and differentiation, inflammatory response, DNA repair, etc. Diosgenin significantly inhibited HSC-3 cell activity. The genes such as AKT1, MET1, SRC1, APP1, CCND1, MYC, PTGS2, AR, NFKB1, BIRC2, MDM2, BCL2L1, MMP2, may be important targets of its action, not only their expression was regulated by diosgenin but also their proteins had a high binding energy with diosgenin. These results suggest that diosgenin may have a therapeutic effect on OSCC through AKT1, MMP2 and other targets and multiple signaling pathways, which is of potential clinical value.

The Prognostic and Immune Significance of BZW2 in Pan-Cancer and its Relationship with Proliferation and Apoptosis of Cervical Cancer.

BACKGROUND: Basic leucine zipper and W2 domains 2 (BZW2), a member of the basic domain leucine zipper superfamily of transcription factors, has been implicated in the development and progression of various cancers. However, the precise biological role of BZW2 in pan-cancer datasets remains to be explored. This study aimed to assess the prognostic significance of BZW2 and its immune-related signatures in various tumors. METHODS: Our study investigated the expression, epigenetic modifications, and clinical prognostic relevance of BZW2 using multi-omics data in different cancer types. Additionally, the immunological characteristics, tumor stemness, drug sensitivity, and correlation of BZW2 with immunotherapy response were explored. Finally, in vitro experiments were conducted to assess the impact of BZW2 knockdown on Hela cells, a cell line derived from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). RESULTS: BZW2 exhibited elevated expression levels in various tumor tissues and significantly impacted the prognosis of different cancer types. BZW2 emerged as an independent prognostic factor in CESC. We found that copy number amplification and methylation levels of BZW2 were associated with its mRNA expression. Immunological analyses revealed that BZW2 shapes a non-inflamed immunosuppressive tumor microenvironment across multiple cancers. Furthermore, our cell experiments demonstrated that BZW2 knockdown reduced proliferation, migration, and apoptosis activities in CESC cells. CONCLUSIONS: BZW2 promotes cancer progression by shaping a non-inflamed immunosuppressive tumor microenvironment. Additionally, BZW2 was shown to significantly influence the proliferation, migration, and apoptosis of CESC cells.