Prognostic value of glycolysis markers in head and neck squamous cell carcinoma: a meta-analysis.
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC7993722 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCircular RNAs (circRNAs) have been found to have potential biological applications against tumors in humans. This study aimed to evaluate the diagnostic, prognostic, and clinicopathological value of circRNAs in head and neck squamous cell carcinoma (HNSCC).MethodsThe PubMed, Web of Science, EMBASE, and the Cochrane Library were comprehensively searched for the relevant studies before October 20, 2021. Statistical analysis was performed based on STATA 15.0, Meta-DiSc 1.4, and RevMan 5.3 software.ResultsA total of 55 reports regarding 56 kinds of circRNA were studied in this meta-analysis, including 23, 38, and 26 articles on diagnosis, prognosis, and clinicopathological features, respectively. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) were 0.78, 0.84, and 0.87, respectively. Besides, the upregulation of oncogenic circRNAs was significantly associated with poorer overall survival (OS) (HR=2.25, p < 0.05) and disease-free interval (DFS) (HR=1.92, p < 0.05). In contrast, the elevated expression of tumor suppressor circRNAs was associated with a favorable prognosis (HR=0.50, p < 0.05). In addition, the high expression of oncogenic circRNAs was associated with the tumor size (OR=3.59, p < 0.05), degree of differentiation (OR=1.89, p < 0.05), TNM stage (OR=2.35, p < 0.05), lymph node metastasis (OR=1.85, p < 0.05), and distant metastasis (OR=3.42, p < 0.05). Moreover, the expression of tumor suppressor circRNAs was associated with improved clinicopathological features (lymph node metastasis: OR=0.25, p < 0.05).ConclusionsCircRNAs could serve as potential predictive indicators and be useful for the diagnosis, prognosis, and identification of clinicopathological features in HNSCC.
| S-EPMC9280010 | biostudies-literature
Project description:BackgroundThe CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue.MethodsWe analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results.ResultsCompared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05).ConclusionsThe results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
| S-EPMC9952890 | biostudies-literature
Project description:Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes (CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.
| S-EPMC7408128 | biostudies-literature
Project description:BackgroundThe induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal population. Thus, there might be associations between the frequencies of HLA alleles and the survival of tumor patients.MethodsThis issue was studied in a cohort of 84 patients with head and neck squamous cell carcinomas (HNSCCs) of different localizations. The cohort was followed up for more than 10 years. HLA-A/B/C CTS-PCR-SSP typing at 1 field level from blood samples was performed, and the results were correlated with survival.ResultsHLA-A*02 was the most prevalent allele in our cohort and was present in 51.1% of patients. The HLA-A*25 and HLA-C*06 alleles exhibited a significantly higher frequency in cancer patients than in the normal population of 174 blood and kidney donors (p = 0.02 and p = 0.01, respectively, Fisher's exact test). For HLA-C*04, a negative impact on overall survival in univariate analysis (p = 0.045) and a negative, but statistically insignificant effect on survival toward poorer survival in multivariate analysis (HR: 1.82; 95% CI: 0.99-3.34, p = 0.053) were observed. In addition, HLA-A*02 was also beneficial for overall survival and progression-free survival in multivariate analysis (HR 0.54; 95% CI: 0.31-0.92; p = 0.023).ConclusionHLA-A*02 allele expression might not only predict better survival but might also indicate superior tumor antigen presentation and, thus, help to select patients who could benefit from T-cell-dependent immunotherapies.
| S-EPMC9367389 | biostudies-literature
Project description:Glycolysis is highly upregulated in head and neck squamous cell carcinoma (HNSCC). HNSCC glycolysis is an important contributor to disease progression and decreases sensitivity to radiation or chemotherapy. Despite therapeutic advances, the survival rates for HNSCC patients remain low. Understanding glycolysis regulation in HNSCC will facilitate the development of effective therapeutic strategies for this disease. In this review, we will evaluate the regulation of altered HNSCC glycolysis and possible therapeutic approaches by targeting glycolytic pathways.
| S-EPMC5300767 | biostudies-literature
Project description:BackgroundMetastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated.MethodsPLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU's association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis.ResultsPLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all p < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU's function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell.ConclusionsPLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU's oncogene role in HNSCC.
| S-EPMC7812932 | biostudies-literature
Project description:The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of the MET copy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Surgically resected HNSCC samples were subjected to immunohistochemical and H-score analysis of c-Met expression and silver in situ hybridization analysis of MET amplification and copy number gains. c-Met expression varied, with mean and median H-scores (scale: 0-300 scale) of 61.2 and 60.0, respectively. The lowest and highest expression levels were observed in SCC of the larynx and oral cavity, respectively. MET copy number gains were observed in 16.9% of cases (67/339) and were associated with c-Met protein expression. High c-Met expression, determined according to MET gain status, was associated with an inferior overall survival rate, especially among completely resected cases. In conclusion, our robust analysis revealed that c-Met expression in HNSCCs varied according to anatomical site, correlated with MET copy number gains, and was associated with poor prognosis. This c-Met expression analysis method, which is based on the MET gain status, appears to appropriately predict high-risk HNSCC patients in the context of anti-MET therapeutic decisions.
| S-EPMC5166528 | biostudies-literature
Project description:Head and neck cancer (HNC) is the fifth most common cancer worldwide. In this study, we performed an integrative analysis of the discovery set and established an eight-gene signature for the prediction of prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Univariate Cox analysis was used to identify prognosis-related genes (with P < 0.05) in the GSE41613, GSE65858, and TCGA-HNSC RNA-Seq datasets after data collection. We performed LASSO Cox regression analysis and identified eight genes (CBX3, GNA12, P4HA1, PLAU, PPL, RAB25, EPHX3, and HLF) with non-zero regression coefficients in TCGA-HNSC datasets. Survival analysis revealed that the overall survival (OS) of GSE41613 and GSE65858 datasets and the progression-free survival(DFS)of GSE27020 and GSE42743 datasets in the low-risk group exhibited better survival outcomes compared with the high-risk group. To verify that the eight-mRNA prognostic model was independent of other clinical features, KM survival analysis of the specific subtypes with different clinical characteristics was performed. Univariate and multivariate Cox regression analyses were used to identify three independent prognostic factors to construct a prognostic nomogram. Finally, the GSVA algorithm identified six pathways that were activated in the intersection of the TCGA-HNSC, GSE65858, and GSE41613 datasets, including early estrogen response, cholesterol homeostasis, oxidative phosphorylation, fatty acid metabolism, bile acid metabolism, and Kras signaling. However, the epithelial-mesenchymal transition pathway was inhibited at the intersection of the three datasets. In conclusion, the eight-gene prognostic signature proved to be a useful tool in the prognostic evaluation and facilitate personalized treatment of HNSCC patients.
| S-EPMC8252784 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) is a group of tumours which exhibit low 5 year survival rates. Thus, there is an urgent need to identify biomarkers that may improve the clinical utility of patients with HNSCC. Emerging studies support a role of toll-like receptors (TLRs) in carcinogenesis. Therefore, this systematic review and meta-analysis was performed to assess the prognostic value of TLR immunoexpression in HNSCC patients. We compiled the results of thirteen studies comprising 1825 patients, of which six studies were deemed qualified for quantitative synthesis. The higher immunoexpression of TLR-1 to 5 and 9 was associated with a worsening of the clinical parameters of patients with HNSCC. Furthermore, induced levels of TLR-3, 4, 5, 7 and 9 were found to predict the patients' survival time. The meta-analysis revealed that TLR-7 overexpression is associated with a decreased mortality risk in HNSCC patients (HR 0.51; 95%CI 0.13-0.89; I2 34.6%), while a higher expression of TLR-5 predicted shorter, but non-significant, survival outcome. In conclusion, this review suggests that TLRs may represent some prognostic value for patients with HNSCC. However, due to small sample sizes and other inherent methodological limitations, more well designed studies across different populations are still needed before TLRs can be recommended as a reliable clinical risk-stratification tool.
| S-EPMC7582583 | biostudies-literature
Project description:A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. Kaplan-Meier survival analysis revealed significant correlations between gain of 3q25-27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.
| S-EPMC2394495 | biostudies-other