Dataset Information

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer.

ABSTRACT:

Background

Head and neck squamous cell cancer (HNSCC) is a common malignant cancer. We aimed to explore prognostic cuproptosis-related lncRNAs (CRLs) and prognostic risk models for HNSCC.

Methods

The transcriptome profiles and clinical data were obtained from the TCGA database, and 19-cuproptosis-related genes (CRGs) were acquired from previous studies. Then, the prognostic model based on seven CRLs was established. We analysed its value to evaluate the prognosis, drug sensitivity, and tumour immune functions of patients with HNSCC. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT‒PCR) to validate the seven CRLs.

Results

We established a 7-CRL signature. Kaplan‒Meier (K-M) curve analysis demonstrated a significantly preferable prognosis in the low-risk group. Multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor. Nomogram, ROC curve, and principal component analysis indicated that the signature presented significant predictive capability. Moreover, most of the high-risk group showed lower levels of IC₅₀ for certain chemotherapy drugs, such as cisplatin, cytarabine, docetaxel, doxorubicin, etoposide, gemcitabine, methotrexate, paclitaxel, and dasatinib. Finally, the expression of AP001372.2, MIR9-3HG, AL160314.2, POLH-AS1, and AL109936.2 was upregulated, while AC090587.1 and WDFY3-AS2 were downregulated in HNSCC cell lines compared with normal cell lines by qRT‒PCR.

Conclusions

The 7-CRL signature was presented to be a novel biomarker for predicting prognosis for HNSCC.

SUBMITTER: Liu X

PROVIDER: S-EPMC9652850 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer.

Liu Xiajing X Cheng Wenwei W Li Heqing H Song Yexun Y

Cancer cell international 20221111 1

<h4>Background</h4>Head and neck squamous cell cancer (HNSCC) is a common malignant cancer. We aimed to explore prognostic cuproptosis-related lncRNAs (CRLs) and prognostic risk models for HNSCC.<h4>Methods</h4>The transcriptome profiles and clinical data were obtained from the TCGA database, and 19-cuproptosis-related genes (CRGs) were acquired from previous studies. Then, the prognostic model based on seven CRLs was established. We analysed its value to evaluate the prognosis, drug sensitivity ...[more]

PMID: 36369058

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Project description:Background: Cuproptosis has been recognized as a novel regulatory cell death, which has been confirmed to promote the occurrence and development of tumors. However, whether cuproptosis-related lncRNA has an impact on the prognosis of squamous cell carcinoma of the head and neck (HNSCC) is still unclear. Methods: In total, 501 HNSCC tumor samples and 44 normal were downloaded from the TCGA database. Cuproptosis-related lncRNAs were obtained by co-expressed analysis. We got prognostic lncRNA that was associated with cuproptosis by using univariate Cox regression analysis and LASSO Cox regression. Then we constructed and validated the prognostic signature of HNSCC and analyzed the immune landscape of the signature. Results: The Prognostic Signature is based on 10 cuproptosis-related lncRNAs including AC090587.1, AC004943.2, TTN-AS1, AL162458.1, AC106820.5, AC012313.5, AL132800.1, WDFY3-AS2, CDKN2A-DT, and AL136419.3. The results of overall survival, risk score distribution, and survival status in the low-risk group were better than those in the high-risk group. In addition, all immune checkpoint genes involved were significantly different between the two risk groups (p < 0.05). The risk score was positively correlated with Eosinophils. M0 and M2 phenotype macrophages, mast cells activated, NK cells activated, and negatively related with B cells naive, mast cells resting, plasma cells, CD8T cells, T cells follicular helper, T cells regulatory (Tregs). Consensus clustering was identified in molecular subtypes of HNSC. More high-risk samples concentrated in Cluster1, which had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score and Single Nucleotide Polymorphisms (SNP) alternation than Cluster2. Conclusion: Our study elucidated the correlation between cuproptosis-related lncRNA with prognosis and immune landscape of HNSCC, which may provide references for further research on the exploration of the mechanism and functions of the prognosis for HNSCC.

Project description:BackgroundThe purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism-related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC).MethodsThe details of human cuproptosis and copper metabolism-related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed.ResultsThe 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC.ConclusionsOur results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.

Project description:BackgroundCopper is an indispensably mineral element involved in various metabolic processes and functions in the active sites of many metalloproteins. Copper dysregulation is associated with cancers such as osteosarcoma (OS), the most common primary bone malignancy with invasiveness and metastasis. However, the causality between cuproptosis and OS remains elusive. We aim to identify cuproptosis-related long non-coding RNAs (lncRNAs) for osteosarcomatous prognosis, immune microenvironment response, and immunotherapy.MethodsThe Person correlation and differential expression analysis were used to identify differentially expressed cuproptosis-related lncRNAs (CRLs). The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct the CRL signature. The Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) curve, internal validation, independent prognostic analysis, and nomograph were used to evaluate the prognostic value. The functional enrichment, tumor microenvironment, immunotherapy and chemotherapy response between the two distinct groups were further explored using a series of algorithms. The expression of signature CRLs was verified by real-time quantitative polymerase chain reaction (RT-qPCR) in OS cell lines.ResultsA novel CRL signature consisting of four CRLs were successfully identified. The K-M survival analysis indicated that the OS patients in the low-risk groups had a better prognosis than that in the high-risk group. Then, the ROC curve and subgroup survival analysis confirmed the prognostic evaluation performance of the signature. Equally, the independent prognostic analysis demonstrated that the CRL signature was an independently predicted factor for OS. Friends analysis determined the hub genes that played a critical role in differentially expressed genes between two distinct risk groups. In addition, the risk score was related to immunity status, immunotherapy response, and chemotherapeutic drug sensitivity. Finally, the expression of these signature CRLs detected by RT-qPCR was consistent with the bioinformatic analysis results.ConclusionIn summary, our study confirmed that the novel CRL signature could effectively evaluate prognosis, tumor immune microenvironment, and immunotherapy response in OS. It may benefit for clinical decision-making and provide new insights for personalized therapeutics.

Dataset Information

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer.

Background

Methods

Results

Conclusions

Publications

Identification and validation of cuproptosis-related LncRNA signatures as a novel prognostic model for head and neck squamous cell cancer.

Similar Datasets

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