Pan-cancer analysis of a novel indicator of necroptosis with its application in human cancer DOI Creative Commons
Aibin Liu, Yanyan Li, Lin Shen

et al.

Aging, Journal Year: 2022, Volume and Issue: 14(18), P. 7587 - 7616

Published: Sept. 26, 2022

As a type of programmed cell death, necroptosis is thought to play dual role in tumorigenesis. However, comprehensive assessment necroptosis-related regulators across human cancers has not been reported. Therefore, this study, we established quantitative index evaluate the rate and determine its correlations with clinical prognosis, signaling pathways molecular features, immune infiltration regulation, immunotherapy, chemotherapy sensitivity cancers. Our results indicated that score can act as favorable or risky prognostic factor various cancer types. A gene set variation analysis suggested significantly associated immune- inflammation-related pathways, growth apoptosis, energy metabolism. Furthermore, affect tumor microenvironment immunity effect on different There crosstalk between components necroptosis, pyroptosis, ferroptosis autophagy multiple types Finally, be an indicator immunotherapy effectiveness cells. study presents characterization cancers, highlights potential necroptotic effects provides new insights into development individualized treatments applications immunotherapy.

Language: Английский

Identification and Validation of the lncRNA MYOSLID as a Regulating Factor of Necroptosis and Immune Cell Infiltration in Colorectal Cancer following Necroptosis-Related LncRNA Model Establishment DOI Open Access
Zhiwei Wu, Fan Zhang, Yaohui Wang

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(18), P. 4364 - 4364

Published: Sept. 7, 2022

Necroptosis is a newly defined form of programmed cell death that plays an important role in cancers. However, necroptosis-related lncRNAs (NRLs) involved colorectal cancer (CRC) have not yet been thoroughly studied.In this study, 4-NRL model was developed based on the least absolute shrinkage and selection operator (LASSO) algorithm. A series informatic, vitro vivo analyses were applied to validate prognostic value potential function hub lncRNA MYOSLID.The exhibited excellent capacity for prediction overall survival other clinicopathological features CRC patients using Kaplan-Meier (K-M) curves receiver operating characteristic (ROC) curves. Furthermore, significant difference levels immune cells, such as CD4 memory T cells activated mast between two risk groups observed. The low-risk had higher expression checkpoints, PDCD1 (PD-1) CD274 (PD-L1). MYOSLID, our model, tissues than normal tissues. Knockdown MYOSLID induced necroptosis inhibited proliferation vivo. Interestingly, knockdown also increased percentage CD4+ CD8+ subcutaneously transplanted tumours.Our promising biomarker can be used predict clinical outcomes patients, regulating infiltration CRC.

Language: Английский

Citations

7
Identification of necroptosis-related subtypes, development of a novel signature, and characterization of immune infiltration in colorectal cancer DOI Creative Commons
Mengyu Sun, Xiaoyu Ji, Meng Xie

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 5, 2022

Necroptosis, a type of programmed cell death, has recently been extensively studied as an important pathway regulating tumor development, metastasis, and immunity. However, the expression patterns necroptosis-related genes (NRGs) in colorectal cancer (CRC) their potential roles microenvironment (TME) have not elucidated. We explored NRGs 1247 samples from genetics transcriptional perspective. Based on consensus clustering algorithm, we identified NRG molecular subtypes gene subtypes, respectively. Furthermore, constructed signature for predicting overall survival time verified predictive ability model. Using ESTIMATE, CIBERSORT, ssGSEA algorithms, assessed association between above scores immune infiltration. Most were differentially expressed CRC tissues normal tissues. found that distinct exhibited different expression, patients' prognosis, checkpoint infiltration characteristics. The calculated can be used to classify patients into high-risk low-risk groups, with group corresponding reduced function, greater risk dysfunction escape. Our comprehensive analysis demonstrated role clinicopathological features, TME. These findings help us deepen our understanding landscape, lay foundation effectively assessing patient outcomes promoting more effective immunotherapy.

Language: Английский

Citations

6
Necrotic related-lncRNAs: Prediction of prognosis and differentiation between cold and hot tumors in head and neck squamous cell carcinoma DOI Creative Commons
Yujing Shi, Yumeng Zhang,

Nian Zuo

et al.

Medicine, Journal Year: 2023, Volume and Issue: 102(23), P. e33994 - e33994

Published: June 9, 2023

Treatment of head and neck squamous cell carcinoma (HNSCC) is a substantial clinical challenge due to the high local recurrence rate chemotherapeutic resistance. This project seeks identify new potential biomarkers prognosis prediction precision medicine improve this condition. A synthetic data matrix for RNA transcriptome datasets relevant information on HNSCC normal tissues was downloaded from Genotypic Tissue Expression Project The Cancer Genome Atlas (TCGA). necrosis-associated long-chain noncoding RNAs (lncRNAs) were identified by Pearson correlation analysis. Then 8-necrotic-lncRNA models in training, testing entire sets established through univariate Cox (uni-Cox) regression Lasso-Cox regression. Finally, prognostic ability model evaluated via survival analysis, nomogram, regression, clinicopathological receiver operating characteristic (ROC) curve. Gene enrichment principal component immune analysis risk group semi-maximum inhibitory concentration (IC 50 ) also conducted. Correlations between score infiltration, checkpoint molecules, somatic gene mutations, anti-cancer drug sensitivity analyzed. Eight lncRNAs (AC099850.3, AC243829.2, AL139095.4, SAP30L-AS1, C5orf66-AS1, LIN02084, LIN00996, MIR4435-2HG) developed patients. distribution, status, time, expression standards these compared low- high-risk groups sets. Kaplan–Meier showed low-risk patients had significantly better prognosis. ROC curves revealed an acceptable predictive value TCGA training stratified indicated that 8 factors independent various parameters. We recombined into 2 clusters Consensus ClusterPlus R package according expressions necrotic lncRNAs. Significant differences found IC clusters, suggesting characteristics can be used evaluate efficacy chemotherapy immunotherapy. may serve as signature provide clues individualized immunotherapy

Language: Английский

Citations

3
HtrA3: a promising prognostic biomarker and therapeutic target for head and neck squamous cell carcinoma DOI Creative Commons
Yan Chen, Jianfeng Yang,

Hangbin Jin

et al.

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e16237 - e16237

Published: Oct. 10, 2023

The dysregulation of the human high-temperature requirement A (HtrA) family serine proteases is associated with many malignancies. However, there are few reports on HtrAs in head and neck squamous cell carcinoma (HNSCC). aim this study was to investigate expression, prognostic value, biological functions HNSCC.The RNA-sequencing data clinical HNSCC were downloaded from Cancer Genome Atlas (TCGA) database. GSE30784 GSE31056 datasets Gene Expression Omnibus (GEO) database used for further verification. This explored differential expression assessed their potential impact prognosis patients using a survival module. Correlations between characteristics HtrA levels then Wilcoxon rank sum test. Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG), Set Enrichment Analysis (GSEA) performed "clusterProfile" R software. Pearson/Spearman correlation test applied analyze relationship immune infiltration level/checkpoint genes. Validation carried out by RT-PCR western blot lines (Fadu Cal-27) non-tumorigenic bronchial epithelium cells (BEAS-2B). Finally, through transfection, CCK-8, Ki-67 immunofluorescence, flow cytometry assays, effect HtrA3 knockdown malignant behavior explored.The gene significantly upregulated patient age, TNM stage, TP53 mutation status TCGA-HNSCC cohort. High expressions HtrA1/3 shorter overall survival, progress-free interval, lower disease-specific HNSCC. nomogram constructed validated. HtrA-related genes enriched response apoptosis pathway. In addition, showed significant correlations B cells, M DC infiltration, checkpoint (CD276, TNFRSF14). blot. Results vitro experiments indicated that inhibits proliferation FaDu Cal-27 while concurrently promoting apoptosis.HtrA3 shows as both marker promising therapeutic target HNSCC, highlighting its relevance importance future research applications.

Language: Английский

Citations

3
Pan-cancer analysis of a novel indicator of necroptosis with its application in human cancer DOI Creative Commons
Aibin Liu, Yanyan Li, Lin Shen

et al.

Aging, Journal Year: 2022, Volume and Issue: 14(18), P. 7587 - 7616

Published: Sept. 26, 2022

As a type of programmed cell death, necroptosis is thought to play dual role in tumorigenesis. However, comprehensive assessment necroptosis-related regulators across human cancers has not been reported. Therefore, this study, we established quantitative index evaluate the rate and determine its correlations with clinical prognosis, signaling pathways molecular features, immune infiltration regulation, immunotherapy, chemotherapy sensitivity cancers. Our results indicated that score can act as favorable or risky prognostic factor various cancer types. A gene set variation analysis suggested significantly associated immune- inflammation-related pathways, growth apoptosis, energy metabolism. Furthermore, affect tumor microenvironment immunity effect on different There crosstalk between components necroptosis, pyroptosis, ferroptosis autophagy multiple types Finally, be an indicator immunotherapy effectiveness cells. study presents characterization cancers, highlights potential necroptotic effects provides new insights into development individualized treatments applications immunotherapy.

Language: Английский

Citations

5