Identification of Five Ferroptosis-Related LncRNAs as Novel Prognosis and Diagnosis Signatures for Renal Cancer

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 8

Published: Jan. 18, 2022

Background: Ferroptosis is a novel regulated cell death that characterized by iron-dependent oxidative damage. Renal cancer the second most common of urinary system, which highly correlated with iron metabolism. The aim our present study was to identify suitable ferroptosis-related prognosis signatures for renal cancer. Methods: We downloaded RNA-seq count data from Cancer Genome Atlas database and used DESeq2, Survival, Cox regression analyses screen signatures. Results: identified 5 differentially expressed lncRNAs (FR-DELs) (DOCK8-AS1, SNHG17, RUSC1-AS1, LINC02609, LUCAT1) be independently overall survival (OS) patients risk assessment model diagnosis constructed those FR-DELs could well predict outcome Conclusion: Our not only suggested as but also provided strategies other cancers in screening biomarkers.

Language: Английский

---

Immunometabolism in the tumor microenvironment and its related research progress

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 31, 2022

The tumor immune microenvironment has been a research hot spot in recent years. cytokines and metabolites the can promote occurrence development of various ways help cells get rid surveillance system complete escape. Many studies have shown that existence is an important reason for failure immunotherapy. impact on systematic study. current this aspect may be only tip iceberg, relative lack integrity, related to heterogeneity tumor. This review mainly discusses status glucose metabolism lipid microenvironment, including phenotype microenvironment; effects these metabolic methods their three Impact: regulatory T (Tregs), tumor-associated macrophages (TAM), natural killer (NK cells); targeted At end article,the potential relationship between Ferroptosis years also briefly described.

Language: Английский

---

Prognosis and personalized treatment prediction in lung adenocarcinoma: An in silico and in vitro strategy adopting cuproptosis related lncRNA towards precision oncology

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 15, 2023

Background: There is a rapid increase in lung adenocarcinomas (LUAD), and studies suggest associations between cuproptosis the occurrence of various types tumors. However, it remains unclear whether plays role LUAD prognosis. Methods: Dataset TCGA-LUAD was treated as training cohort, while validation cohort consisted merged datasets GSE29013, GSE30219, GSE31210, GSE37745, GSE50081. Ten studied cuproptosis-related genes (CRG) were used to generated CRG clusters cluster-related differential expressed gene (CRG-DEG) clusters. The differently lncRNA that with prognosis ability CRG-DEG put into LASSO regression for signature (CRLncSig). Kaplan-Meier estimator, Cox model, receiver operating characteristic (ROC), time-dependent AUC (tAUC), principal component analysis (PCA), nomogram predictor further deployed confirm model's accuracy. We examined connections other forms regulated cell death, including apoptosis, necroptosis, pyroptosis, ferroptosis. immunotherapy demonstrated by applying eight mainstream immunoinformatic algorithms, TMB, TIDE, immune checkpoints. evaluated potential drugs high risk CRLncSig LUADs. Real-time PCR human tissues performed verify expression pattern, signature's pan-cancer's also assessed. Results: A nine-lncRNA signature, CRLncSig, built owning prognostic power applied cohort. Each confirmed differentially real world real-time PCR. correlated 2,469/3,681 (67.07%) apoptosis-related genes, 13/20 (65.00%) necroptosis-related 35/50 (70.00%) pyroptosis-related 238/380 (62.63%) ferroptosis-related genes. Immunotherapy suggested status, checkpoints, KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, CD28, linked closely our potentially suitable targets. For those high-risk patients, we found three agents, gemcitabine, daunorubicin, nobiletin. Finally, some lncRNAs play vital cancer need more attention studies. Conclusion: results this study can help determine outcome effectiveness immunotherapy, well better select targets therapeutic agents.

Language: Английский

---

Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 13, 2025

Liver injury is an independent risk factor for multiple organ dysfunction and high mortality in patients with sepsis. However, the pathological mechanisms therapeutic strategies sepsis-associated liver have not been fully elucidated. Time-restricted feeding (TRF) a promising dietary regime, but its role septic remains unknown. Using 16S rRNA gene sequencing, Q200 targeted metabolomics, transcriptomics, germ-free mice, Hmgcs2/Lpin1 knockout Aml12 cells experiments, we revealed that TRF can mitigate by modulating gut microbiota, particularly increasing Lactobacillus murinus (L. murinus) abundance, which was significantly reduced mice. Further study live L. could markedly elevate serum levels of metabolite 3-hydroxybutyrate (3-HB) alleviate sepsis-related injury, while key enzyme 3-HB synthesis (3-hydroxy-3-methylglutaryl-CoA synthase 2, Hmgcs2) negated this protective effect. Additionally, were positively correlated abundance negatively indicators patients, demonstrating strong predictive value (AUC = 0.8429). Mechanistically, inhibited hepatocyte ferroptosis activating PI3K/AKT/mTOR/LPIN1 pathway, reducing ACSL4, MDA, LPO, Fe2+ levels. This demonstrates reduces microbiota to increase murinus, elevates activate inhibit ferroptosis. Overall, elucidates mechanism against identifies as potential target biomarker, thereby providing new insights into clinical management diagnosis injury.

Language: Английский

---

Multi-omics integration reveals YWHAE as a key mediator of ferroptosis in ARDS

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 22, 2025

Language: Английский

---

Ferroptosis in Lung Cancer: From Molecular Mechanisms to Prognostic and Therapeutic Opportunities

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

Published: Dec. 2, 2021

Lung cancer is the second commonly diagnosed malignancy worldwide and has highest mortality rate among all cancers. Tremendous efforts have been made to develop novel strategies against lung cancer; however, overall survival of patients still low. Uncovering underlying molecular mechanisms this disease can open up new horizons for its treatment. Ferroptosis a newly discovered type programmed cell death that, in an iron-dependent manner, peroxidizes unsaturated phospholipids results accumulation radical oxygen species. Subsequent oxidative damage caused by ferroptosis contributes tumor cells. Therefore, understanding appears as promising strategy induce selectively. According evidence published now, significant numbers research done identify regulators cancer. review aims provide comprehensive standpoint address these molecules’ prognostic therapeutic values, hoping that road future studies field will be paved more efficiently.

Language: Английский

---

Construction and validation of a novel gene signature for predicting the prognosis of osteosarcoma

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Jan. 24, 2022

Abstract Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The high-throughput sequencing technology has shown potential abilities to illuminate pathogenic genes in OS. This study was designed find a powerful gene signature that can predict clinical outcomes. We selected OS cases with expression and survival data TARGET-OS dataset GSE21257 datasets as training cohort validation cohort, respectively. univariate Cox regression Kaplan–Meier analysis were conducted determine prognostic from cohort. These underwent LASSO regression, which then generated signature. harvested signature’s predictive ability further examined by analysis, receiver operating characteristic (ROC curve). More importantly, we listed similar studies recent year compared theirs ours. Finally, performed functional annotation, immune relevant correlation identification, infiltrating better he mechanism cells’ roles prognosis ability. A seventeen-gene ( UBE2L3, PLD3, SLC45A4, CLTC, CTNNBIP1, FBXL5, MKL2, SELPLG, C3orf14, WDR53, ZFP90, UHRF2, ARX, CORT, DDX26B, MYC, SLC16A3 ) regression. confirmed having strong stable capacity all studied cohorts several statistical methods. revealed superiority our after comparing it predecessors, GO KEGG annotations uncovered specifically action related Six signatures, including PRF1, CD8A, HAVCR2, LAG3, CD274, GZMA identified associating immune-infiltrating recognized vital T cells CD8 Mast activated, potentially support robust accurately prognosis. immunotherapy targets activated linked power.

Language: Английский

---

Identification of cuproptosis-related subtypes in lung adenocarcinoma and its potential significance

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

Published: Oct. 3, 2022

Cuproptosis is a novel and unique cell death mode that has attracted significant interest in recent years. Little currently known about whether cuproptosis-related genes (CRGs) are associated with the pathophysiology survival of patients lung adenocarcinoma (LUAD). The present study sought to characterize transcriptional genetic alteration CRGs LUAD its potential significance tumor microenvironment predicting prognosis LUAD. secondary eventual aim was role immunotherapy response clinical value combined TNM stage. We found several CRGs, including FDX1, DLD, SLC31A1, MTF1, were enriched macrophages our single-cell RNA-seq data. Three distinct molecular subtypes identified correlated clinicopathological characteristics, prognosis, biological pathways, (TME) developed gene score (CRG_score) validated it three independent cohorts subtypes. low CRG_score group, characterized by greater immune score, immunophenoscore (IPS), lower dysfunction exclusion (TIDE) T-cell had better suggesting group responded more favorably immunotherapy, which anti-PD-1/L1 cohort (IMvigor210). In contrast, high sensitive targeted therapy chemotherapy, higher cancer stem (CSC) index half-maximal inhibitory concentration (IC50) for many drugs. Given established crosstalk between stage, we an accurate nomogram application CRG_score. Taken together, rigorous comprehensive examination their functions TME, drug sensitivity, prognosis. These findings improve current understanding cuproptosis LUAD, paving way assessment tailored treatment this patient population.

Language: Английский

---

A novel DNA methylation signature to improve survival prediction of progression-free survival for testicular germ cell tumors

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

Published: March 7, 2023

Abstract This study aimed to develop a nomogram for predicting the progression-free survival (PFS) of testicular germ cell tumors (TGCT) patients based on DNA methylation signature and clinicopathological characteristics. The profiles, transcriptome data, clinical information TGCT were obtained from Cancer Genome Atlas (TCGA) database. Univariate Cox, lasso stepwise multivariate Cox regression applied identify prognostic CpG sites-derived risk signature. Differential expression analysis, functional enrichment immunoinfiltration chemotherapy sensitivity feature correlation analysis performed elucidate differences among groups. A integrating features was further established evaluated likewise. score model 7 sites developed found exhibit significant different survival, staging, radiotherapy, subgroups. There 1452 differentially expressed genes between high- low-risk groups, with 666 being higher 786 lower expressed. Genes highly significantly enriched in immune-related biological processes related T-cell differentiation pathways; meanwhile, down-regulated extracellular matrix tissue organization-related involved multiple signaling pathways such as PI3K-AKT. As compared group, high-risk group had decreased lymphocyte infiltration (including B-cell) increased macrophage (M2 macrophages). They also showed etoposide bleomycin chemotherapy. Three clusters by consensus clustering distinct features, scores each cluster different. Multivariate that scores, age, chemotherapy, staging independent factors PFS TGCT, results used formulate validated have C-index 0.812. Decision curve superior other strategies prediction TGCT. In this study, we successfully signature, which might serve useful tool PFS, immunoinfiltration, patients.

Language: Английский

---

Comprehensive Analysis of Programmed Cell Death Signature in the Prognosis, Tumor Microenvironment and Drug Sensitivity in Lung Adenocarcinoma

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

Published: May 18, 2022

Programmed cell death (PCD) is a process that regulates the homeostasis of cells in body, and it plays an important role tumor immunity. However, expression profile clinical characteristics PCD-related genes remain unclear. In this study, we comprehensively analysed PCD with microenvironment (TME), drug sensitivity, immunothearapy response, evaluated their prognostic value through systematic bioinformatics methods.We identified 125 regulatory factors, which were expressed differently lung adenocarcinoma (LUAD) normal tissues. 32 related associated LUAD by univariate Cox analysis. 23 gene signature was constructed, all patients Cancer Genome Atlas (TCGA) dataset stratified as low-risk or high-risk groups according to risk score. This had powerful value, validated three independent data sets subtypes. Additionally, has unique properties TME. Further analysis showed different have immune infiltration, inflammation profile, pathways, addition, group better immunotherapy response higher levels multiple checkpoints lower Tumor dysfunction exclusion (TIDE) score, while sensitive chemotherapeutic drugs because its IC50. short, first model predict prognosis immunological status based on genes. It may be used predictor achieve customized treatment LUAD.

Language: Английский

---