Expression and Prognostic Characteristics of Ferroptosis-Related Genes in Colon Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhu J
PROVIDER: S-EPMC8199073 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundColon cancer (CC) is a common gastrointestinal malignant tumor with high heterogeneity in clinical behavior and response to treatment, making individualized survival prediction challenging. Ferroptosis is a newly discovered iron-dependent cell death that plays a critical role in cancer biology. Therefore, identifying a prognostic biomarker with ferroptosis-related genes provides a new strategy to guide precise clinical decision-making in CC patients.MethodsAlteration in the expression profile of ferroptosis-related genes was initially screened in GSE39582 dataset involving 585 CC patients. Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were combined to further identify a novel ferroptosis-related gene signature for overall survival prediction. The prognostic performance of the signature was validated in the GSE17536 dataset by Kaplan-Meier survival curve and time-dependent ROC curve analyses. Functional annotation of the signature was explored by integrating GO and KEGG enrichment analysis, GSEA analysis and ssGSEA analysis. Furthermore, an outcome risk nomogram was constructed considering both the gene signature and the clinicopathological features.ResultsThe prognostic signature biomarker composed of 9 ferroptosis-related genes accurately discriminated high-risk and low-risk patients with CC in both the training and validation datasets. The signature was tightly linked to clinicopathological features and possessed powerful predictive ability for distinct clinical subgroups. Furthermore, the risk score was confirmed to be an independent prognostic factor for CC patients by multivariate Cox regression analysis (p < 0.05). Functional annotation analyses showed that the prognostic signature was closely correlated with pivotal cancer hallmarks, particularly cell cycle, transcriptional regulation, and immune-related functions. Moreover, a nomogram with the signature was also built to quantify outcome risk for each patient.ConclusionThe novel ferroptosis-related gene signature biomarker can be utilized for predicting individualized prognosis, optimizing survival risk assessment and facilitating personalized management of CC patients.
| S-EPMC8280527 | biostudies-literature
Project description:BackgroundAutophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related (ATG) genes in the occurrence and development of gastric cancer (GC).MethodsData from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues. The association of ATG genes expression with clinicopathologic indicators was evaluated by The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Moreover, using the TCGA datasets, the prognostic role of ATG genes was assessed. A nomogram was further built to assess the independent prognostic factors.ResultsThe expression of autophagy-related genes AMBRA1, ATG4B, ATG7, ATG10, ATG12, ATG16L2, GABARAPL2, GABARAPL1, ULK4 and WIPI2 showed differences between cancer and normal tissues. After verification, ATG14 and ATG4D were significantly associated with TNM stage. ATG9A, ATG2A, and ATG4D were associated with T stage. VMP1 and ATG4A were low-expressed in patients without lymph node metastasis. No gene in autophagy pathway was associated with M stage. Further multivariate analysis suggested that ATG4D and MAP1LC3C were independent prognostic factors for GC. The C-index of nomogram was 0.676 and the 95% CI was 0.628 to 0.724.ConclusionOur study provided a comprehensive illustration of ATG genes expression characteristics in GC. Abnormal expressions of the ubiquitin-like conjugated system in ATG genes plays a key role in the occurrence of GC. ATG8/LC3 sub-system may play an important role in development and clinical outcome of GC. In the future, it is necessary to further elucidate the alterations of specific ATG8/LC3 forms in order to provide insights for the discovery, diagnosis, or targeting for GC.
| S-EPMC7866901 | biostudies-literature
Project description:Background: Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40-80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer. Methods: We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas and analyzed differentially expressed genes based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology functions. On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curvevalidation were then performed. Risk curves and nomograms were generated for both groups to predict survival. Finally, RT-qPCR was applied to analyze gene expression. Results: Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, and JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Conclusion: This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.
| S-EPMC8635965 | biostudies-literature
Project description:ObjectiveThis study examined the mechanism through which plumbagin induces ferroptosis of colon cancer cells.MethodsCCK-8 assay was performed to examine the viability of colon cancer cells (SW480 and HCT116 cells) after they were treated with 0-, 5-, 10-, 15- and 20-μmol/L plumbagin. Colony formation assay and Transwell assay were used to examine the effects of 15-μmol/L plumbagin on the proliferation, invasive ability. The ferroptosis of SW480 and HCT116 cells and the expression of p-p53, p53 and SLC7A11 were analysed. The effects of blocking necrosis, apoptosis and ferroptosis on the anti-cancer effects of plumbagin were examined. After p53 was silenced, the effects of plumbagin on proliferation, invasion, ferroptosis and SLC7A11 expression were assessed. A tumour-bearing nude mouse model was used to examine the effects of p53 silencing and/or plumbagin on tumour growth, ferroptosis and SLC7A11 expression.ResultsPlumbagin inhibited the proliferation of SW480 and HCT116 cells and their invasive and colony-forming abilities. It increased Fe2+ levels but significantly decreased GSH and GPX4 levels. When ferroptosis was inhibited, the effects of plumbagin on colon cancer cells were significantly alleviated. Plumbagin promoted the expression and phosphorylation of p53 and inhibited the mRNA and protein levels of SLC7A11. Silencing of p53 counteracted the effects of plumbagin on the ferroptosis and biological behaviour of SW480 and HCT116 cells. In mouse models of colon cancer, silencing of p53 attenuated the tumour-suppressing effects of plumbagin as well as its inhibitory effects on the protein level of SLC7A11 and restored the expression of GSH and GPX4.ConclusionPlumbagin promotes ferroptosis and inhibits cell proliferation and invasion by decreasing the protein expression of SLC7A11 through p53.
| S-EPMC11002553 | biostudies-literature
Project description:Colon cancer is a common and leading cause of death and malignancy worldwide. N6-methylation of adenosine (m6A) is the most common reversible mRNA modification in eukaryotes, and it plays a crucial role in various biological functions in vivo. Dysregulated expression and genetic changes of m6A regulators have been correlated with tumorigenesis, cancer cell proliferation, tumor microenvironment, and prognosis in cancers. This study used RNA-seq and colon cancer clinical data to explore the relationship between N6-methylation and colon cancer. Based on the seven m6A regulators related to prognosis, three molecular subgroups of colon cancer were identified. Surprisingly, we found that each subgroup had unique survival characteristics. We then identified three subtypes of tumors based on 299 m6A phenotype-related genes, and one subtype was characterized as an immunosuppressive tumor and patients in this subtype may be more suitable for immunotherapy than other subtypes. Finally, using m6A-related genes and clinical information from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model could be used to predict the prognosis of patients in clinics.
| S-EPMC7926939 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been reported to be prognostic factors for cancer. Ferroptosis is an iron-dependent process of programmed cell death. Here, we established a ferroptosis-related lncRNA (frlncRNA) pair signature and revealed its prognostic value in colon adenocarcinoma (COAD) by analyzing the data from The Cancer Genome Atlas (TCGA). FrlncRNAs were identified based on co-expression analysis using the Pearson correlation. Differentially expressed frlncRNAs (DEfrlncRNAs) were recognized and paired, followed by prognostic assessment using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) penalized Cox analysis was used to determine and construct a risk score prognostic model, by which the receiver operating characteristic (ROC) curves for predicting the overall survival (OS) were conducted. Following the evaluation of whether it was an independent prognostic factor, correlations between the risk score model and clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants were investigated. In total, 148 DEfrlncRNA pairs were identified, 25 of which were involved in a risk score prognostic signature. The area under ROC curves (AUCs) representing the predictive effect for 1-, 3-, and 5-year survival rates were 0.860, 0.885, and 0.934, respectively. The risk score model was confirmed as an independent prognostic factor and was significantly superior to the clinicopathological characteristics. Correlation analyses showed disparities in clinicopathological characteristics, hypoxia- and immune-related factors, and somatic variants, as well as specific signaling pathways between high- and low-risk groups. The novel risk score prognostic model constructed by pairing DEfrlncRNAs showed promising clinical prediction value in COAD.
| S-EPMC8544324 | biostudies-literature
Project description:Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, and TFRC, were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that TFRC overexpression induced the proliferation and invasion of PCa cell lines in vitro. These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.
| S-EPMC8320699 | biostudies-literature
Project description:BackgroundThyroid cancer is the most common endocrine malignancy. Most PTC patients have a good prognosis; however, there are 5-20% of PTC patients with extra-thyroidal invasion, vascular invasion, or distant metastasis who have relatively poor prognoses. The aim of this study is to find new and feasible molecular pathological markers and therapeutic targets for early identification and appropriate management.MethodsThe GEO and TCGA databases were used to gather gene expression data and clinical outcomes. Based on gene expression and clinical parameters, we developed a ferroptosis-related gene-based prognostic model and a nomogram. CCK-8, wound-healing, and transwell assays were conducted to explore the proliferation, migration, and invasion abilities of thyroid cancer cells.ResultsWe found 75 genes associated with ferroptosis that were differentially expressed between normal thyroid tissue and thyroid cancer tissues. The prognostic values of the 75 ferroptosis-related gene expressions were evaluated using the TCGA-THCA dataset, and five (AKR1C3, BID, FBXW7, GPX4, and MAP3K5) of them were of significance. Following that, we chose AKR1C3 as the subject for further investigation. By combining gene expression and clinical parameters, we developed a ferroptosis-related gene-based prognostic model with an area under the curve (AUC) of 0.816, and the nomogram also achieved good predictive efficacy for the three-year survival rate of thyroid cancer patients. Knocking down AKR1C3 enhances thyroid cancer cell proliferation, invasion, and migration abilities.ConclusionsA ferroptosis-related gene-based prognostic model was constructed that provided unique insights into THCA prognosis prediction. In addition, AKR1C3 was found to be a progression promoter in thyroid cancer cell lines.
| S-EPMC9222385 | biostudies-literature
Project description:BackgroundThe prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.MethodsWe retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.ResultsGene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.ConclusionsThe FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
| S-EPMC8201541 | biostudies-literature
Project description:Mounting evidence supports that the malignant phenotypes of cancers are defined not only by the intrinsic activity of tumor cells but also by immune cells that are recruited and activated in tumor-related microenvironment. Here, we developed a diagnostic and prognostic model for colon cancer, based on expression profiles of immune-related genes and immune cell component. As a result, we found that B cell infiltration ratio, CD4+ T cells, as well as immune-related genes of TRIB3, CHGA, CASP7, LGALS4, LEP, NOX4, IL17A, and HSPD1 may be highly relevant with clinical outcome of colon cancer.
| S-EPMC7227137 | biostudies-literature