Ferroptosis-Related Long Non-Coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Tang Y
PROVIDER: S-EPMC7975700 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor, which makes the prognosis prediction challenging. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death, which could affect cancer development. However, the prognostic value of ferroptosis-related long non-coding RNA (lncRNA) in HNSCC is still limited. Methods: In the current study, we employed the DESeq2 method to characterize the differentially expressed ferroptosis-related genes (FEGs) between cancer and normal samples. Next, the FEG-related lncRNAs (FElncRNAs) were identified using Spearman's correlation analysis and multiple permutation hypotheses. Subsequently, LASSO and stepwise multivariate Cox regression analyses were undertaken to recognize the prognosis-related FElncRNA signature (PFLS) and risk scores. Results: Herein, we first identified 60 dysregulated FEGs and their co-expressed FElncRNAs in HNSCC. Then, we recognized a set of six FElncRNAs PFLS (SLCO4A1-AS1, C1RL-AS1, PCED1B-AS1, HOXB-AS3, MIR9-3HG, and SFTA1P) for predicting patients' prognostic risks and survival outcomes. We also assessed the efficiency of PFLS in the test set and an external validation cohort. Further parsing of the tumor immune microenvironment showed the PFLS was closely associated with immune cell infiltration abundances. Notably, the low-risk group of the PFLS showed a higher MHC score and cytolytic activity (CYT) score than the high-risk group, implying the low-risk group may have greater tumor surveillance and killing ability. In addition, we observed that the expression levels of two immune checkpoints (ICPs), i.e., programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), showed significant associations with patients' risk score, prompting the role of the PFLS in ICP blockade therapy. Finally, we also constructed a drug-PFLS network to reinforce the clinical utilities of the PFLS. Conclusion: In summary, our study indicated that FElncRNAs played an important role in HNSCC survival prediction. Identification of PFLS will contribute to the development of novel anticancer therapeutic strategies.
| S-EPMC8718757 | biostudies-literature
Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by late diagnosis and poor prognosis. The aim of this study was to identify a novel ferroptosis-related DNA methylation signature as an alternative diagnosis index for patients with HNSCC.MethodsMethylome and transcriptome data of 499 HNSCC patients, including 275 oral squamous cell carcinoma (OSCC) samples, were obtained from The Cancer Genome Atlas (TCGA). An additional independent methylation dataset of 50 OSCC patients from the NCBI Gene Expression Omnibus (GEO) database was used for validation. As an index of ferroptosis activity, the ferroptosis score (FS) of each patient was inferred from the transcriptome data using single-sample gene set enrichment analysis. Univariate, multivariate, and LASSO Cox regression analyses were used to select CpG sites for the construction of a ferroptosis-related DNA methylation signature for diagnosis of patients.ResultsWe initially inferred the FS of each TCGA HNSCC patient and divided the samples into high- and low-FS subgroups. Results showed that the high-FS subgroup displayed poor overall survival. Moreover, 378 differentially methylated CpG sites (DMCs) were identified between the two HNSCC subgroups, with 16 selected to construct a 16-DNA methylation signature for risk prediction in HNSCC patients using the LASSO and multivariate Cox regression models. Relative operating characteristic (ROC) curve analysis showed great predictive efficiency for 1-, 3-, and 5-year HNSCC survival using the 16-DNA methylation signature. Its predictive efficiency was also observed in OSCC patients from the TCGA and GEO databases. In addition, we found that the signature was associated with the fractions of immune types in the tumor immune microenvironment (TIME), suggesting potential interactions between ferroptosis and TIME in HNSCC progression.ConclusionsWe established a novel ferroptosis-related 16-DNA methylation signature that could be applied as an alternative tool to predict prognosis outcome in patients with HNSCC, including OSCC.
| S-EPMC8767683 | biostudies-literature
Project description:The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.
| S-EPMC8629675 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and has a high mortality. Ferroptosis, an iron-dependent form of programmed cell death, plays a crucial role in tumor suppression and chemotherapy resistance in cancer. However, the prognostic and clinical values of ferroptosis-related genes (FRGs) in HNSCC remain to be further explored. In the current study, we constructed a ferroptosis-related prognostic model based on the Cancer Genome Atlas database and then explored its prognostic and clinical values in HNSCC via a series of bioinformatics analyses. As a result, we built a four-gene prognostic signature, including FTH1, BNIP3, TRIB3, and SLC2A3. Survival analysis showed that the high-risk group presented significantly poorer overall survival than the low-risk group. Moreover, the ferroptosis-related signature was found to be an independent prognostic predictor with high accuracy in survival prediction for HNSCC. According to immunity analyses, we found that the low-risk group had higher anti-tumor immune infiltration cells and higher expression of immune checkpoint molecules and meanwhile corelated more closely with some anti-tumor immune functions. Meanwhile, all the above results were validated in the independent HSNCC cohort GSE65858. Besides, the signature was found to be remarkably correlated with sensitivity of common chemotherapy drugs for HNSCC patients and the expression levels of signature genes were also significantly associated with drug sensitivity to cancer cells. Overall, we built an effective ferroptosis-related prognostic signature, which could predict the prognosis and help clinicians to perform individualized treatment strategy for HNSCC patients.
| S-EPMC8566369 | biostudies-literature
Project description:BackgroundFerroptosis is an iron-dependent programmed cell death modality that may have a tumor-suppressive function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic predictor for bladder cancer (BCa).MethodsWe retrieved BCa-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Least absolute shrinkage and selection operator regression (LASSO) and Cox regression models were used to identify and develop predictive models and validate the model accuracy. Finally, we explored the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes.ResultsKaplan-Meier analyses screened 11 differentially expressed lncRNAs associated with poor BCa prognosis. The signature (AUC = 0.720) could be utilized to predict BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in the low-risk group. TCGA showed that the p53 signaling pathway, ferroptosis, Kaposi sarcoma - associated herpesvirus infection, IL - 17 signaling pathway, MicroRNAs in cancer, TNF signaling pathway, PI3K - Akt signaling pathway and HIF - 1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were differentially expressed between the two risk groups. m6A methylation-related genes were significantly differentially expressed between the two risk groups.ConclusionA new ferroptosis-associated lncRNAs signature developed for predicting the prognosis of BCa patients will improve the treatment and management of BCa patients.
| S-EPMC9245204 | biostudies-literature
Project description:BackgroundThe prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients.MethodsThe mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups.ResultsA prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator's contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status.ConclusionThis study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.
| S-EPMC8290602 | biostudies-literature
Project description:The Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common human cancer, causing 350,000 individuals die worldwide each year. The overall prognosis in HNSCC patients has not significantly changed for the last decade. Complete understanding of the molecular mechanisms in HNSCC carcinogenesis could allow an earlier diagnosis and the use of more specific and effective therapies. In the present study we used deep sequencing to characterize small non-coding RNAs (sncRNAs) in serum from HNSCC patients and healthy donors. We identified, for the first time, a multi-marker signature of 3 major classes of circulating sncRNAs in HNSCC, revealing the presence of circulating novel and known miRNAs, and tRNA- and YRNA-derived small RNAs that were significantly deregulated in the sera of HNSCC patients compared to healthy controls. By implementing a triple-filtering approach we identified a subset of highly biologically relevant miRNA-mRNA interactions and we demonstrated that the same genes/pathways affected by somatic mutations in cancer are affected by changes in the abundance of miRNAs. Therefore, one important conclusion from our work is that during cancer development, there seems to be a convergence of oncogenic processes driven by somatic mutations and/or miRNA regulation affecting key cellular pathways.
| S-EPMC4662488 | biostudies-literature
Project description:IntroductionThe incidence of head and neck squamous cell carcinoma (HNSCC), one of the most prevalent tumors, is increasing rapidly worldwide. Cuproptosis, as a new copper-dependent cell death form, was proposed recently. However, the prognosis value and immune effects of cuproptosis-related lncRNAs (CRLs) have not yet been elucidated in HNSCC.MethodsIn the current study, the expression pattern, differential profile, clinical correlation, DNA methylation, functional enrichment, univariate prognosis factor, and the immune effects of CRLs were analyzed. A four-CRL signature was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm.ResultsResults showed that 20 CRLs had significant effects on the stage progression of HNSCC. Sixteen CRLs were tightly correlated with the overall survival (OS) of HNSCC patients. Particularly, lnc-FGF3-4 as a single risk factor was upregulated in HNSCC tissues and negatively impacted the prognosis of HNSCC. DNA methylation probes of cg02278768 (MIR9-3HG), cg07312099 (ASAH1-AS1), and cg16867777 (TIAM1-AS1) were also correlated with the prognosis of HNSCC. The four-CRL signature that included MAP4K3-DT, lnc-TCEA3-1, MIR9-3HG, and CDKN2A-DT had a significantly negative effect on the activation of T cells follicular helper and OS probability of HNSCC. Functional analysis revealed that cell cycle, DNA replication, and p53 signal pathways were enriched.DiscussionA novel CRL-related signature has the potential of prognosis prediction in HNSCC. Targeting CRLs may be a promising therapeutic strategy for HNSCC.
| S-EPMC10394648 | biostudies-literature
Project description:SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09-1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.
| S-EPMC5785960 | biostudies-literature
Project description:Infection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure. A patient cohort (n = 295) with mainly non-OPSCC (72.9%) and a low prevalence of HPV16-related tumors (8.8%) was analyzed by MassARRAY to determine a previously established prognostic methylation score (MS). Kaplan-Meier revealed a highly significant correlation between a high MS and a favorable survival for OPSCC (P = 0.0004) and for non-OPSCC (P<0.0001), which was confirmed for all HNSCC by multivariate Cox regression models (HR: 9.67, 95% CI [4.61-20.30], P<0.0001). Next, we established a minimal methylation signature score (MMSS), which consists of ten most informative of the originally 62 CpG units used for the MS. The prognostic value of the MMSS was confirmed by Kaplan-Meier analysis for all HNSCC (P<0.0001) and non-OPSCC (P = 0.0002), and was supported by multivariate Cox regression models for all HNSCC (HR: 2.15, 95% CI [1.36-3.41], P = 0.001). In summary, the MS and the MMSS exhibit an excellent performance as prognosticators for survival, which is not limited by the anatomical site, and both could be implemented in future clinical trials.
| S-EPMC4846111 | biostudies-literature