Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma

OncoTargets and Therapy, Journal Year: 2021, Volume and Issue: Volume 14, P. 5373 - 5383

Published: Dec. 1, 2021

Gastric cancer (GC) ranks fifth in global incidence and third cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type regulated cell death mediated by RIP1, RIP3, MLKL. found to be involved antitumor immunity the immunotherapy.LASSO Cox regression analysis performed construct prognostic signature. Bioinformatics lncRNA-miRNA-mRNA regulatory axis. qRT-PCR verify expression hub gene STAD.Most necroptosis regulators were upregulated, while mRNA level TLR3, ALDH2, NDRG2 downregulated STAD versus gastric tissues. genetic mutation copy number variation regulator also summarized. GO KEGG pathways revealed that these mainly programmed necrotic TNF signaling pathway. A necroptosis‑related signature based on four genes (EZH2, PGAM5, TLR4, TRAF2) had good performance predicting patients. We identified lncRNA SNHG1/miR-21-5p/TLR4 axis progression STAD. Verification study suggested TLR4 upregulated correlated with poor overall survival. Moreover, clinical stage independent factors affecting patients.We comprehensive bioinformatics Further should confirm our result.

Language: Английский

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Construction of an Immune-Related Six-lncRNA Signature to Predict the Outcomes, Immune Cell Infiltration, and Immunotherapy Response in Patients With Hepatocellular Carcinoma

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 2, 2021

Background Hepatocellular carcinoma (HCC) is one of the world’s most lethal malignant tumors with a poor prognosis. Growing evidence has been demonstrating that immune-related long non-coding RNAs (lncRNAs) are relevant to tumor microenvironment (TME) and can help assess effects immunotherapy evaluate one’s This study aims identify an lncRNA signature for prospective assessment prognosis in HCC. Method We downloaded HCC RNA-seq data clinical information from The Cancer Genome Atlas (TCGA) project database. first used ESTIMATE TME. Then, we conducted cox regression analysis construct prognostic riskScore. then applied univariate Cox regression, multivariate principal components (PCA), receiver operating characteristic (ROC) curve, stratification analyses confirm our previous assessments. Afterward, employed gene set enrichment (GSEA) explore biological processes pathways. Besides, CIBERSORT estimate abundance tumor-infiltrating immune cells (TIICs). Furthermore, investigated relationship between checkpoint genes. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) assays demonstrate expression six lncRNAs. Results identified lncRNAs — MSC-AS1, AC145207.5, SNHG3, AL365203.2, AL031985.3, NRAV which show ability stratify patients into high-risk low-risk groups significantly different survival rates. ROC, confirmed six-lncRNA was novel independent factor patients. group illustrated contrasting distributions PCA. GSEA suggested involved associated infiltration cells. it linked critical genes could predict immunotherapy’s response. qRT-PCR demonstrated were differentially expressed cell lines normal hepatic lines. Conclusion In summary, outcomes, infiltration, response hepatocellular carcinoma.

Language: Английский

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Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 11, 2021

Background: Stroke is one of the most common deadly diseases with an estimated 780,000 new cases globally, which ischemic stroke accounts for over 80% all cases. Ferroptosis a form programmed cell death that plays vital role in many diseases, including and heart diseases. The ferroptosis-related gene diagnosis, prognosis, or therapy was not fully clarified. Methods: Ferroptosis-related differentially expressed genes (DEGs) were identified by bioinformatic analysis GSE16561 GSE22255 datasets. Subsequently, receiver operator characteristic (ROC) monofactor performed to evaluate diagnostic value biomarkers stroke. Results: A total 10 DEGs vs. normal control. GO KEGG revealed these mainly enriched response oxidative stress, HIF-1 signaling pathway, ferroptosis, lipid, atherosclerosis. Moreover, random forest model suggested three biomarkers, namely, PTGS2, MAP1LC3B, TLR4, Interestingly, expression TLR4 upregulated ROC demonstrated good performance diagnosis also verified using GSE22255. We transcription factor regulation network co-expressed protein biomarkers. Several potential therapeutic compounds corresponding stroke, Zinc12503187 (Conivaptan), Zinc3932831 (Avodart), Zinc64033452 (Lumacaftor), Zinc11679756 (Eltrombopag), Zinc100378061 (Naldemedine), Zinc3978005 (Dihydroergotamine). Conclusion: Our results as providing more evidence about ferroptosis

Language: Английский

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Construction of a Prognostic Signature of 10 Autophagy-Related lncRNAs in Gastric Cancer

International Journal of General Medicine, Journal Year: 2022, Volume and Issue: Volume 15, P. 3699 - 3710

Published: April 1, 2022

Autophagy plays a double-edged sword role in cancers. LncRNAs could regulate cancer initiation and development at various levels. However, the of autophagy-related lncRNAs (ARlncs) gastric (GC) remains indistinct.GC gene expression profile clinical data were acquired from Cancer Genome Atlas (TCGA). The prognostic signature composed ARlncs was established via cox regression analysis. Kaplan-Meier (K-M) survival curve adopted to show overall (OS). Independence reliability risk visualized by analysis ROC curve. A nomogram constructed analyzed Immune infiltrating cells check points also analyzed.A which stratified GC patients into high- low-risk groups according score calculated 10 including LINC01094, AC068790.7, AC090772.1, AC005165.1, PVT1, LINC00106, AC026368.1, AC090912.3, AC013652.1, UICLM. Patients high-risk group showed poor prognosis (p<0.001). Cox an independent factor Areas under curves (AUC) for predicting OS outweighed age, gender, grade, T, M N, suggested signature. with signature, M, N age its AUC 1-, 3-, 5-year 0.700, 0.730, 0.757 respectively, good reliability. Macrophage M2, T cell CD8+ CD4+ memory resting had greatest difference between two CIBERSORE-ABS algorithm CD274 (PD-L1), PDCD1 (PD-1) PDCD1LG2 (PD-L2) expressed higher (p<0.05), implied that immunotherapy may be choice these patients.The based on can serve as efficacious predictor guide immunotherapies precise treatment patients.

Language: Английский

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PI3K/Akt signalling pathway-associated long noncoding RNA signature predicts the prognosis of laryngeal cancer patients

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 7, 2023

Abstract The PI3K/Akt signalling pathway is associated with the occurrence and development of tumours significantly affects prognosis patients. We established a predictive signature based on to predict RNA-seq clinical data laryngeal cancer patients were downloaded from Cancer Genome Atlas (TCGA) database. Three lncRNAs ( MNX1-AS1 , LINC00330 LSAMP-AS1 ) selected through univariate, multivariate Cox log-rank test analysis establish prognostic signature. then divided into high-risk low-risk groups their risk score. In TCGA training set, survival time group was shorter than that (P < 0.01). Follicular helper T cells lower in P = 0.022), CCR, inflammation promotion, parainflammation, type I IFN immune function suppressed. results drug sensitivity suggest sensitive AKT inhibitors. establishment also verified data. can facilitate migration, invasion, vitality vitro, vice versa. Moreover, p-AKT (Ser473) p-PI3K highly activated overexpressing abovementioned three lncRNAs. pathway-associated has good effect.

Language: Английский

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LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis

Inflammation, Journal Year: 2022, Volume and Issue: 45(5), P. 1936 - 1949

Published: April 23, 2022

Language: Английский

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Integrated analysis of TCGA data identifies endoplasmic reticulum stress-related lncRNA signature in stomach adenocarcinoma

ONCOLOGIE, Journal Year: 2023, Volume and Issue: 26(2), P. 221 - 237

Published: Dec. 29, 2023

Abstract Objectives To investigaed the role of endoplasmic reticulum stress (ERS)-related long non-coding RNAs (lncRNAs) in stomach adenocarcinoma (STAD) using TCGA data. Methods This study integrated clinical, transcriptomic, and tumor data from Cancer Genome Atlas (TCGA). The expression ERS genes was evaluated, alongside their association with identified lncRNAs. Gene set enrichment analysis immune cell infiltration were performed to elucidate biological pathways influenced by these Results five lncRNAs – AC012055.1, LINC01235, LINC00571, LINC02073, CFAP61-AS1 strongly correlated cancer prognosis. A prognostic model based on developed validated across low- high-risk groups. Potential associated uncovered through GSEA. Additionally, screening drugs potentially effective against STAD, highlighting co-expressed as probable therapeutic targets. Conclusions research offers detailed insights into molecular mechanisms enhancing understanding potential targets showing promise for clinical applications.

Language: Английский

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A risk score model with five long non-coding RNAs for predicting prognosis in gastric cancer: an integrated analysis combining TCGA and GEO datasets

PeerJ, Journal Year: 2021, Volume and Issue: 9, P. e10556 - e10556

Published: Feb. 9, 2021

Gastric cancer (GC) is one of the most common carcinomas digestive tract, and prognosis for these patients may be poor. There evidence that some long non-coding RNAs(lncRNAs) can predict with GC. However, few lncRNA signatures have been used to prognosis. Herein, we aimed construct a risk score model based on expression five lncRNAs GC provide new potential therapeutic targets.We performed differentially expressed survival analyses identify survival-ralated by using patient profile data from The Cancer Genome Atlas (TCGA) database. We then established formula including In addition, verify prognostic value this model, two independent Gene Expression Omnibus (GEO) datasets, GSE62254 (N = 300) GSE15459 200), were employed as validation groups.Based characteristics lncRNAs, divided into high or low subgroups. was confirmed in both TCGA GEO datasets. Furthermore, stratification analysis results showed had an stage II-IV constructed nomogram combining clinical factors increase accuracy prediction. Enrichment Kyoto Encyclopedia Genes Genomes (KEGG) suggested are associated multiple occurrence progression-related pathways.The GC, especially those II-IV, targets future.

Language: Английский

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A Novel Six-Gene-Based Prognostic Model Predicts Survival and Clinical Risk Score for Gastric Cancer

Frontiers in Genetics, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 22, 2021

Background: Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related genes (ARGs) have rarely been analyzed gastric (GC). The purpose of this study was analyze ARGs GC using bioinformatic analysis identify new biomarkers for predicting the overall survival (OS) patients with GC. Methods: gene expression profiles clinical data were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) datasets, two other datasets (the Human Database Molecular Signatures Database). Lasso, univariate, multivariate Cox regression analyses performed OS-related ARGs. Finally, six-ARG model identified as prognostic indicator risk-score model, performance based on Kaplan-Meier test ROC curve. Estimate calculations used assess immune status Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) employed investigating functions terms associated model-related Results: six ARGs, DYNLL1 , PGK2 HPR PLOD2 PHYHIP CXCR4 Lasso analyses. Survival revealed that OS high-risk group significantly lower than low-risk ( p &lt; 0.05). curves risk score exhibited better respect OS. Multivariate indicated an independent predictor not affected by most traits suppression several biological process terms, such extracellular structure organization matrix organization. Moreover, P13K-Akt signaling pathway, focal adhesion, MAPK pathway. Conclusions: This presents potential would aid determining best patient-specific course

Language: Английский

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The Emerging Role of Thymopoietin-Antisense RNA 1 as Long Noncoding RNA in the Pathogenesis of Human Cancers

DNA and Cell Biology, Journal Year: 2021, Volume and Issue: 40(7), P. 848 - 857

Published: June 7, 2021

Long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of multiple human cancers. An accumulating body researches have investigated thymopoietin antisense RNA 1 (TMPO-AS1) as a newly discovered lncRNA, which functions an oncogenic lncRNA that is upregulated various malignancies associated with poor prognosis. Many studies detected abnormally high expression levels TMPO-AS1 cancers, such lung cancer, breast colorectal cancer (CRC), hepatocellular carcinoma, CRC, gastric ovarian thyroid esophageal Wilms tumor, cervical retinoblastoma, bladder osteosarcoma, prostate cancer. has been subsequently demonstrated to pivotal role tumorigenesis progression. The aberrantly expressed acts competing endogenous (ceRNA) inhibits miRNA expression, thus activating downstream oncogenes. This study comprehensively summarizes aberrant expressions reported current literature explains relevant biological regulation mechanisms carcinogenesis tumor Corresponding indicated potential value promising biomarker or target for therapy.

Language: Английский

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