Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck.
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SUBMITTER: Mori S
PROVIDER: S-EPMC8409292 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction Angiosarcoma of the head and neck is a rare vascular sarcoma associated with high rates of local recurrence and distant metastasis and a poor prognosis. Objective We describe our experience treating patients with angiosarcoma of the head and neck to evaluate the outcomes, patterns of failure, and current treatments. Methods We identified six patients with angiosarcoma of the head and neck and treated at our institution between 2000 and 2013. We compared our results to the literature from 1979 to 2013. Results Mean follow-up was 42 months. Local recurrence rate was 50% with disease-specific survival and 2-year disease-free survival rates of 33.3 and 20%, respectively. Prognostic factors included tumor size > 5 cm and surgical margin status, with no correlation between histologic grade and survival. Combined-modality therapy was only used for aggressive tumors with positive surgical margins but is suggested to improve local control and overall survival. Conclusions Our data series supports that angiosarcoma of the head and neck has a high rate of recurrence and is associated with a poor prognosis, despite current combined-modality therapy. The study highlights the importance of attaining negative margins during surgical resection, the utility of adjuvant therapies, as well as the need for continued research in developing new management strategies.
| S-EPMC4490918 | biostudies-other
Project description:Breast cancer anti-estrogen resistance protein 3 (BCAR3) is involved in anti-estrogen resistance and other important aspects of breast cancer. However, the role of BCAR3 in other solid tumors remains unclear. The relationship between the clinicopathologic characteristics of head and neck squamous cell carcinoma (HNSCC) patients and BCAR3 was analyzed using the Wilcoxon’s signed-rank test and logistic regression. The association between BCAR3 expression and clinicopathologic features and survival was analyzed using Cox regression and the Kaplan–Meier method. In vivo and in vitro assays were performed to validate the effect of BCAR3 on HNSCC growth. BCAR3-related mRNAs were determined by calculating the Pearson’s correlation coefficient based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and gene set enrichment analysis (GSEA) were used to predict the potential functions of BCAR3. BCAR3 expression is overexpressed in HNSCC and was shown to be associated with perineural invasion (PNI) and poor survival. BCAR3 silencing significantly attenuated the proliferation of HNSCC cells, whereas BCAR3 depletion inhibited tumor growth in vitro. GO and KEGG functional enrichment analyses, and GSEA showed that BCAR3 expression in HNSCC was associated with biological processes, such as cell adhesion, actin binding, cadherin binding, and angiogenesis. BCAR3, which promotes HNSCC growth, is associated with perineural invasion and may be a potential molecular prognostic marker of poor survival in HNSCC.
| S-EPMC8551282 | biostudies-literature
Project description:Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of tumors with variable presentation and clinical behavior. Despite improvements in surgical and radiation therapy techniques, the 5-year survival rate has not improved significantly over the past decades. Thus, there is an urgent need to identify novel markers that may allow for the development of personalized therapeutic approaches. In the present study we evaluated the prognostic role of the expression of genes related to the induction of epithelial mesenchymal transition (EMT). To this aim, a consecutive series of 69 HNSCC were analyzed for the expression of TWIST1, TWIST2, SNAI1, SNAI2, E-Cadherin, N-Cadherin and Vimentin.TWIST1, TWIST2, SNAI1 and SNAI2 were significantly overexpressed in HNSCC, with TWIST2, SNAI1 and SNAI2 being more markedly increased in tumors compared to normal mucosae. The expression of TWIST1 and SNAI2 was associated with upregulation of mesenchymal markers, but failed to correlate with pathological parameters or clinical behaviour. In contrast, we found that upregulation of TWIST2, which was independent of the activation of a mesenchymal differentiation program, correlated with poor differentiation grade (p=0.016) and shorter survival (p=0.025), and identifies a subset of node-positive oral cavity/pharynx cancer patients with very poor prognosis (p less than 0.001). Overall our study suggests that the assessment of TWIST2 expression might help to stratify HNSCC patients for risk of disease progression, pointing to TWIST2 as a potential prognostic marker.
| S-EPMC3282075 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) represents a significant world health problem, with approximately 600,000 new cases being diagnosed annually. The prognosis for patients with HNSCC is poor and, therefore, the identification of biomarkers for screening, diagnosis and prognostication would be clinically beneficial. A limited number of studies have used lipidomics to profile lipid species in the plasma of cancer patients. However, the profile and levels of lysophosphatidic acid (LPA) species have not been examined in HNSCC. In this study, a targeted lipidomics approach using liquid chromatography triple quadrupole mass spectrometry (LCMS/MS) was used to analyse the concentration of LPA (16:0 LPA, 18:0 LPA, 18:1 LPA, 18:2 LPA and 20:4 LPA) in the plasma of patients with oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC), together with healthy controls. The levels of three LPA species (18:1 LPA, 18:2 LPA and 20:4 LPA) were significantly lower in the plasma of OSCC patients, whilst the concentrations of all five LPA species tested were significantly lower in plasma from NPC patients. Furthermore, the order of abundance of LPA species in plasma was different between the control and cancer groups, with 16:0 LPA, 18:0 LPA levels being more abundant in OSCC and NPC patients. Medium to strong correlations were observed using all pairs of LPA species and a clear separation of the normal and tumour groups was observed using PCA analysis. In summary, the results of this study showed that the levels of several LPA species in the plasma of patients with OSCC and NPC were lower than those from healthy individuals. Understanding these variations may provide novel insights into the role of LPA in these cancers.
| S-EPMC7278886 | biostudies-literature
Project description:Core 1 ?1,3-galactosyltransferase (C1GALT1) controls the crucial step of GalNAc-type O-glycosylation and is overexpressed in various human malignancies. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Here we demonstrate that C1GALT1 expression is upregulated in HNSCC tumors and is associated with adverse clinicopathologic features. Moreover, high C1GALT1 expression predicts poor disease-free and overall survivals. C1GALT1 overexpression enhances HNSCC cell viability, migration, and invasion, which can be reversed by erlotinib. Silencing of C1GALT1 suppresses the malignant behavior both in vitro and in vivo. Mass spectrometry and lectin pull-down assays demonstrate that C1GALT1 modifies O-glycans on EGFR. Blocking O-glycan elongation on EGFR by C1GALT1 knockdown decreases EGF-EGFR binding affinity and inhibits EGFR signaling, thereby suppressing malignant phenotypes. Using molecular docking simulations, we identify itraconazole as a C1GALT1 inhibitor that directly binds C1GALT1 and promotes its proteasomal degradation, leading to significant blockade of C1GALT1-mediated effects in HNSCC cells in vitro and in vivo. Collectively, our findings demonstrate a critical role of O-glycosylation in HNSCC progression and highlight the therapeutic potential of targeting C1GALT1 in HNSCC treatment.
| S-EPMC6202324 | biostudies-literature
Project description:Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.
| S-EPMC9214264 | biostudies-literature
Project description:Hypoxanthine phosphoribosyltransferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 gene and head and neck squamous cell carcinomas (HNSCCs) has not been investigated so far. In this study, we first evaluated the expression and clinical value of HPRT1 mRNA and protein in tumor and healthy control tissues. Then, we examined mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. We also performed functional analyses of HPRT1 coexpressed genes and examined the association between HPRT1 expression and drug sensitivity. Both HPRT1 mRNA and protein were significantly higher in HNSCC compared with normal tissues, and up-regulation of HPRT1 was also correlated with age, sex, pathological stage and histological grades of patients with HNSCC. Moreover, HPRT1 and its associated genes were observed to be enriched for several cancer-related pathways, including DNA replication and cell cycle. Finally, patients exhibiting overexpression of the HPRT1 gene may be resistant to abiraterone and sensitive to several drugs, including tozasertib and teniposide. This study demonstrated that the elevated expression of HPRT1 gene is correlated with the progression of HNSCC; thus, this gene may serve as a useful indicator for the early detection, risk stratification and targeted therapy of patients with HNSCC.
| S-EPMC8409317 | biostudies-literature
Project description:ObjectiveTo evaluate the effect of elevated plasma fibrinogen levels on the prognosis of epithelial ovarian cancer (EOC).MethodsWe reviewed the data of 217 patients with advanced-stage EOC between 2000 and 2012, and investigated the prognostic role of elevated plasma fibrinogen levels compared with serum CA-125 levels, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). For further evaluation, we performed a meta-analysis using 5 cohort studies published to July 2015, including our cohort study after a literature review.ResultsAmong the four biomarkers, only plasma fibrinogen levels >485.2 mg/dL were correlated with impaired progression-free survival (PFS) and overall survival (OS) (median, 13.9 vs. 20.3 months and 42.2 vs. 55.4 months; p<0.010). Elevated plasma fibrinogen levels were an independent factor for poor PFS with marginal significance and OS (adjusted hazard ratios [HRs]=1.389 and 1.581; 95% confidence intervals [CIs]=0.979-1.972 and 1.032-2.423, respectively). Furthermore, crude and subgroup meta-analyses demonstrated that elevated plasma fibrinogen levels were associated with impaired PFS and OS in patients with all stage EOC.ConclusionElevated plasma fibrinogen levels be more important for predicting survival than serum CA-125 levels, NLR and PLR in patients with EOC, in particular, advanced-stage disease. Moreover, it may be related to poor prognosis of EOC.
| S-EPMC5391395 | biostudies-literature
Project description:BACKGROUND:Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC. METHODS:Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival. RESULTS:The mean number of methylated genes per sample was 2.05?±?2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5-9 methylated genes had a significantly lower survival rate than that of patients with 0-4 methylated genes (log-rank test, P=?0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P?=?0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P?=?0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P?=?0.028 and P?=?0.006, respectively). Moreover, Patients with 5-9 methylated genes were extremely lower of 5hmC levels (P?=?0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P?<?0.05 and P?<?0.05, respectively). CONCLUSION:We characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.
| S-EPMC6977280 | biostudies-literature
Project description:BackgroundCancer metastasis and recurrence after radiotherapy are the significant causes of poor prognosis in head-neck cancer (HNC). Clinically, it is commonly found that patients with either condition may accompany the outcome of the other. We hypothesized that HNC cells might exhibit a cross-phenotypic attribute between cell invasion and radioresistance. To discover effective biomarkers for the intervention of aggressive cancer at one time, the potential molecules that interplay between these two phenotypes were investigated.Materials and methodsThree isogenic HNC cell sublines with high invasion or radioresistance properties were established. Transcriptomic and bioinformatic methods were used to globally assess the phenotypic-specific genes, functional pathways, and co-regulatory hub molecules. The associations of gene expressions with patient survival were analyzed by Kaplan-Meier plotter, a web-based tool, using the HNSCC dataset (n=500). The molecular and cellular techniques, including RT-qPCR, flow cytometry, cell invasion assay, and clonogenic survival assay, were applied.ResultsThe phenotypic crosstalk between cell invasion and radioresistance was validated, as shown by the existence of mutual properties in each HNC subline. A total of 695 genes was identified in associations with these two phenotypes, including 349 upregulated and 346 downregulated in HNC cells. The focal adhesion mechanism showed the most significant pathway to co-regulate these functions. In the analysis of 20 up-regulatory genes, a general portrait of correlative expression was found between these phenotypic cells (r=0.513, p=0.021), and nine molecules exhibited significant associations with poor prognosis in HNC patients (HR>1, p<0.050). Three hub genes were identified (ITGA6, TGFB1, and NDRG1) that represented a signature of interplayed molecules contributing to cell invasion, radioresistance and leading to poor prognosis. The ITGA6 was demonstrated as a prominent biomarker. The expression of ITGA6 correlated with the levels of several extracellular and apoptotic/anti-apoptotic molecules. Functionally, silencing ITGA6 suppressed cell migration, invasion, and attenuated radioresistance in HNC cells.ConclusionsA panel of interplay molecules was identified that contribute to cell invasion and radioresistance, leading to poor prognosis. These panel molecules, such as ITGA6, may serve as predictive markers of radioresistance, prognostic markers of metastasis, and molecular therapeutic targets for refractory HNC.
| S-EPMC8299304 | biostudies-literature