Prognostic Value of Eight-Gene Signature in Head and Neck Squamous Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu B
PROVIDER: S-EPMC8252784 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:PurposeTo construct a prognostic signature composed of DNA repair genes to effectively predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).MethodsAfter downloading the transcriptome and clinical data of HNSCC from the Cancer Genome Atlas (TCGA), 499 patients with HNSCC were equally divided into training and testing sets. In the training set, 13 DNA repair genes were screened using univariate proportional hazard (Cox) regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a risk model, which was validated in the testing set.ResultsIn the training and testing sets, there were significant differences in the clinical outcomes of patients in the high- and low-risk groups showed by Kaplan-Meier survival curves (P < 0.001). Univariate and multivariate Cox regression analyses showed that the risk score had independent prognostic predictive ability (P < 0.001). At the same time, the immune cell infiltration, immune score, immune-related gene expression, and tumor mutation burden (TMB) of patients with HNSCC were also different between the high- and low-risk groups (P < 0.05). Finally, we screened several chemotherapeutics for HNSCC, which showed significant differences in drug sensitivity between the high- and low-risk groups (P < 0.05).ConclusionThis study constructed a 13-DNA-repair-gene signature for the prognosis of HNSCC, which could accurately and independently predict the clinical outcome of the patient. We then revealed the immune landscape, TMB, and sensitivity to chemotherapy drugs in different risk groups, which might be used to guide clinical treatment decisions.
| S-EPMC8362833 | biostudies-literature
Project description:Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method. Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05). Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.
| S-EPMC8591309 | biostudies-literature
Project description:Objectives: LncRNAs are essential survival prognostic indicators with important biological functions in tumorigenesis and tumor progression. This study aimed to establish a long non-coding RNA (lncRNA) signature that can effectively predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and explore the potential functions of these lncRNAs. Materials and Methods: We re-annotated RNA sequencing and obtained exhaustive RNA-seq data of 269 patients with comprehensive clinical information from the GEO database. Then an 8-lncRNA signature capable of predicting the survival prognosis of HNSCC patients and a nomogram containing this signature were established. Weighted Co-expression Network Construction (WGCNA), Gene Set Enrichment Analysis (GSEA), and Gene Ontology (GO) enrichment were then applied to predict the possible biological functions of the signature and each individual lncRNA. Results: Eight lncRNAs associated with survival in HNSCC patients, including AC010624.1, AC130456.4, LINC00608, LINC01300, MIR99AHG, AC008655.1, AC055758.2, and AC118553.1, were obtained by univariate regression, cox LASSO regression, and multivariate regression. Functionally, patients with high signature scores had abnormal immune functions via GSEA. AC010624.1 and AC130456.4 may participate in epidermal cell differentiation and skin development, and MIR99AHG in the formation of cellular structures. Other lncRNAs in the signature may also participate in important biological processes. Conclusions: Therefore, we established an 8-lncRNA signature that can effectively guide clinical prediction of the prognosis of patients with HNSCC, and individuals with high signature scores may have abnormal immune function.
| S-EPMC6759597 | biostudies-literature
Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous malignant cancer with poor prognosis. Pyroptosis is defined as a novel inflammation-dependent programmed cell death. However, the pyroptosis-associated gene expression in HNSCC and their relationship with prognosis are still indistinct.Material and methodsWe acquired the mRNA expression information of HNSCC patients from publicly available TCGA and GEO databases. We compared the tumor issues and adjacent normal tissues in terms of the gene expression for the purpose of identifying differentially expressed genes (DEGs). Based on these genes, we established a risk signature by the LASSO Cox regression in the TCGA cohort and validated the results in a GEO cohort. We also verified the levels of relevant mRNA expression in the model by RT-qPCR analysis. Eventually, functional enrichment approach was carried out to explore the potential mechanisms.ResultsOur team found a total of 18 differentially expressed genes (DEGs) between the HNSCC and healthy samples, and 4 DEGs displayed a remarkable association with the overall survival (OS) (P < 0.05). A 4-gene signature was constructed, presenting beneficial forecast power in both TCGA and GEO cohorts. Our team categorized patients into a group with high risk and another group with low risk as per the average risk value of the 4-gene feature. The individuals in the low risk group displayed a notably greater OS compared with the high risk one (P < 0.01). The Cox regression study demonstrated the independent forecast capability of the risk score. The receiver operating characteristic approach facilitated the verification of the forecast function of the gene signature. Posterior to verification, 4 genes were aberrantly expressed in the HNSCC and healthy samples. Functional study displayed that these groups presented diverse immunity conditions.ConclusionPyroptosis-associated genes are pivotal for the prognosis of HNSCC and can serve as potential therapeutic targets.
| S-EPMC8575318 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) is a common malignant cancer that accounts for 5-10% of all cancers. This study aimed to identify essential genes associated with the prognosis of HNSCC and construct a powerful prognostic model for the risk assessment of HNSCC. RNAseq expression profile data for the patients with HNSCC were obtained from the TCGA database (GEO). A total of 500 samples with full clinical following-up were randomly divided into a training set and a validation set. The training set was used to screen for differentially expressed lncRNAs. Single-factor survival analysis was performed to obtain lncRNAs that associated with prognosis. A robust likelihood-based survival model was constructed to identify the lncRNAs that are essential for the prognosis of HNSCC. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to serve as the final signature lncRNAs for prognosis. Finally, the prognostic effect of the signature lncRNAs was tested by multi-factor survival analysis and a scoring model for the prognosis of HNSCC was constructed. Moreover, the results of the validation set and the relative expression levels of the signature lncRNAs in the tumour and the adjacent tissue were consistent with the results of the training set. The 5 lncRNAs were distributed among 3 expression modules. Further KEGG pathway enrichment analysis showed that these 3 co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease. Therefore, we proposed that the 5 validated lncRNAs can be used to predict the prognosis of HNSCC patients and can be applied in postoperative treatment and follow-up.
| S-EPMC6189101 | biostudies-literature
Project description:The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, very limited robust and reliable immunological biomarkers have been developed that are capable of estimating prognosis in HNSCC patients. In this study, we aimed to identify the effects of novel immune-related gene signatures (IRGs) that can predict HNSCC prognosis. Based on gene expression profiles and clinical data of HNSCC patient cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, a total of 439 highly variable expressed immune-related genes (including 239 upregulated and 200 downregulated genes) were identified by using differential gene expression analysis. Pathway enrichment analysis indicated that these immune-related differentially expressed genes were enriched in inflammatory functions. After process screening in the training TCGA cohort, six immune-related genes (PLAU, STC2, TNFRSF4, PDGFA, DKK1, and CHGB) were significantly associated with overall survival (OS) based on the LASSO Cox regression model. Integrating these genes with clinicopathological features, a multivariable model was built and suggested better performance in determining patients' OS in the testing cohort, and the independent validation cohort. In conclusion, a well-established model encompassing both immune-related gene signatures and clinicopathological factors would serve as a promising tool for the prognostic prediction of HNSCC.
| S-EPMC8249947 | 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 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:Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan-Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients' overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.
| S-EPMC7785385 | biostudies-literature
Project description:BackgroundDeciphering the immune characteristics within tumors and identifying the immune signals related to the prognostic factor are helpful for the treatment and management of tumor patients. However, systematic analysis of immune signatures in head and neck squamous cell carcinoma (HNSCC) remains largely unstudied.MethodsA total of 718 immune-related genes were extracted from RNA sequencing data from 519 HNSCC patients in the TCGA database, and survival analysis with integrated bioinformatics analyses was performed to build the final predictive prognosis model.ResultsThe 178 survival-associated genes (P < 0.05) participated in important immune functions, including immune cell activation and migration. Multivariate regression analysis using 93 genes (P < 0.01), together with survival-associated clinicopathological parameters, identified 35 independent prognostic factors. The most significant 8 independent factors were CD3E, CD40LG, TNFRSF4, CD3G, CD5, ITGA2B, ABCB1, and TNFRSF13b. The final prognostic model achieved outstanding predictive efficiency with the highest AUC of 0.963.ConclusionOur prognostic model based on the immune signature could effectively predict the prognosis of HNSCC patients, providing novel predictive biomarkers and potential therapeutic targets for HNSCC patients.
| S-EPMC7593737 | biostudies-literature