Dataset Information

A hypoxia-related lncRNA model for prediction of head and neck squamous cell carcinoma prognosis.

ABSTRACT:

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common and highly heterogeneous malignancies worldwide. Increasing studies have proven that hypoxia and related long non-coding RNA (lncRNA) are involved in the occurrence and prognosis of HNSCC. The goal of this work is to construct a risk assessment model using hypoxia-related lncRNAs (hrlncRNAs) for HNSCC prognosis prediction and personalized treatment.

Methods

Transcriptome expression matrix, clinical follow-up data, and somatic mutation data of HNSCC patients were obtained from The Cancer Genome Atlas (TCGA). We used co-expression analysis to identify hrlncRNAs, then screened for differentially expressed lncRNAs (DEhrlncRNAs), and paired these DEhrlncRNAs. The risk model was established through univariate, least absolute shrinkage and selection operator (LASSO), and stepwise multivariate Cox regression. Finally, we assessed the model from multiple perspectives of tumor mutation burden (TMB), tumor immune infiltration, chemotherapeutic sensitivity, immune checkpoint inhibitor (ICI), and functional enrichment.

Results

The risk assessment model included 14 hrlncRNA pairs. The risk score was observed to be a reliable prognostic factor. The high-risk patients had an unfavorable prognosis and significant differences from the low-risk group in TMB and tumor immune infiltration. In the high-risk patients, the common immune checkpoints were down-regulated, including CTLA4 and PDCD1, and the sensibility to paclitaxel and docetaxel was higher. The functional enrichment analysis suggested that the low-risk group was accompanied by activated immune function.

Conclusions

The risk assessment model of 14-hrlncRNA-pairs demonstrated a promising prognostic prediction for HNSCC patients and can guide personalized clinical treatment.

SUBMITTER: Xiang J

PROVIDER: S-EPMC9939198 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

A hypoxia-related lncRNA model for prediction of head and neck squamous cell carcinoma prognosis.

Xiang Junwei J He Yaodong Y Li Yunshan Y Wu Kexuan K Cheng Mengxiang M Wang Yuanyin Y Chen Ran R

Cancer medicine 20220803 3

<h4>Background</h4>Head and neck squamous cell carcinoma (HNSCC) is one of the most common and highly heterogeneous malignancies worldwide. Increasing studies have proven that hypoxia and related long non-coding RNA (lncRNA) are involved in the occurrence and prognosis of HNSCC. The goal of this work is to construct a risk assessment model using hypoxia-related lncRNAs (hrlncRNAs) for HNSCC prognosis prediction and personalized treatment.<h4>Methods</h4>Transcriptome expression matrix, clinical ...[more]

PMID: 35920349

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Project description:BackgroundRecent research has highlighted pyroptosis as a key factor in cancer progression. This study aims to explore the association between pyroptosis-related signatures and overall survival (OS) in head and neck squamous cell carcinoma (HNSC) and develop a pyroptosis-related long non-coding RNA (lncRNA) risk model to predict prognosis and response to immunotherapy in HNSC.MethodsWe extracted expression data for 18 pyroptosis-related genes and identified lncRNA probes specific to HNSC by using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Consensus clustering was performed to categorize HNSC patients into distinct subtypes. A six-lncRNA risk score model was constructed through univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. We evaluated the predictive ability of the lncRNA model for patients' survival and immunotherapy response. Gene expression was evaluated using immunohistochemistry (IHC) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR).ResultsOur analysis revealed two distinct pyroptosis-related subtypes in HNSC patients, Cluster A and Cluster B. Notably, patients in Cluster B exhibited significantly poorer overall survival compared to those in Cluster A. Through differential expression analysis, we identified six lncRNAs (AC002331.1, CTA-384D8.35, RP11-291B21.2, AC006262.5, RP1-27K12.2, and RP11-54H7.4) that were differentially expressed between these clusters. A 6-lncRNA risk score model was developed, which successfully stratified patients into high- and low-risk groups with distinct overall survival outcomes. Validation using RT-qPCR confirmed the differential expression of these six lncRNAs in HNSC tumor tissues compared to adjacent normal tissues, we found that the expression of CTA-384D8.35 was significantly increased in the tumor group (t=-6.203, P<0.001). Furthermore, the 6-lncRNA risk score model demonstrated a significant association with patient response to immunotherapy, with the low-risk group exhibiting a higher objective response rate to immune checkpoint blockade (ICB) therapy and longer survival compared to the high-risk group.ConclusionOur study underscores the role of pyroptosis signatures in HNSC prognosis and identifies two distinct pyroptosis subtypes with differing survival outcomes. The six-lncRNA risk score model offers a valuable tool for predicting patient prognosis and potential benefits from ICB therapy. These findings highlight the importance of pyroptosis and associated lncRNAs in the tumor microenvironment, paving the way for novel targeted therapies in HNSC.

Project description:BackgroundFerrogenesis was strongly associated with tumorigenesis and development, and activating the ferrogenic process was a novel regimen in treating cancer, especially conventional treatment-resistant cancers. The purpose of the article was to construct a ferroptosis-related long noncoding RNAs (FRlncRNAs) signature, regardless of expression levels to effectively predict prognosis and immunotherapeutic response for head and neck squamous cell carcinoma (HNSCC).MethodsThe RNA-seq data for HNSCC and corresponding clinical information were obtained in the TCGA database, and ferroptosis-related genes (FRGs) were extracted in the ferroptosis database. On this basis, differentially expressed FRlncRNAs (DEFRlncRNAs) pairs were identified through coexpression analysis, differential expression analysis, and a fresh pairing algorithm. Then, a risk assessment model was established with univariate Cox, LASSO, and multivariate Cox regression analysis. Finally, we evaluated the model from various aspects, including survival status, clinicopathological characteristics, infiltration status of immune cells, immune functions, chemotherapeutic sensitivity, immune checkpoint inhibitors (ICIs)-related molecules, and N6-methyladenosine (m6A) mRNA status.ResultWe established a signature of 11-DEFRlncRNA pairs related to the prognosis of HNSCC that had AUC values above 0.75 in the one-, three-, and five-year ROC curves, underscoring the high susceptibility and specifiability of predicting HNSCC prognosis. Survival rates were remarkably higher for the low-risk patients than for the high-risk patients, and the signature was significantly correlated with survival, clinical, T, and N stages. Finally, immune cell infiltration status, immune functions, chemotherapeutic sensitivity, and expression levels of ICIs-related and m6A-related molecules were statistically different among different groups.ConclusionOur study established a novel lncRNA signature, which is independent of specific expression levels, could predict patient prognosis, and might have promising clinical applications in HNCSS.

Dataset Information

A hypoxia-related lncRNA model for prediction of head and neck squamous cell carcinoma prognosis.

Background

Methods

Results

Conclusions

Publications

A hypoxia-related lncRNA model for prediction of head and neck squamous cell carcinoma prognosis.

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