Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer
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SUBMITTER: Bi S
PROVIDER: S-EPMC11241446 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND Colorectal cancer (CRC), the most common gastrointestinal cancer, is associated with high mortality rates. Enolase is a major enzyme present in the glycolytic pathway. However, the functional significance of the enolase (ENO) gene family in the pathogenesis of CRC has been unclear. MATERIAL AND METHODS The data associated with 438 CRC patients from The Cancer Genome Atlas database were extracted for analysis. Survival analyses with Cox regression was performed to construct a prognostic signature. We investigated the processes that underlies the correlation between ENO genes and overall survival (OS) using gene set enrichment analysis (GSEA). We then developed a connectivity map to identify candidate target drugs for CRC. RESULTS The multivariate survival analysis showed that low expression of ENO2 and ENO3 had a significant correlation with longer OS. The joint-effects survival analysis indicated that the combined low expression of ENO2 and ENO3 was highly correlated with favorable OS. As indicated by the gene set enrichment analysis (GSEA), the ENO gene is involved in various biological pathways and has multiple roles. Potential pharmacological targets of ENO2 and ENO3 were constructed as well. CONCLUSIONS Low expression levels of both ENO2 and ENO3 were linked to a positive prognosis for CRC. Both ENO2 and ENO3 show promise as prognostic biomarkers for colon cancer patients.
| S-EPMC7401828 | biostudies-literature
Project description:The FXYD gene family comprises seven members that encode a class of small-membrane proteins characterized by an FXYD motif and interact with Na+/K+-ATPase. Until now, the expression patterns and prognostic roles of the FXYD family in colon cancer (CC) have not been systematically reported. Gene expression, methylation, clinicopathological features and the prognoses of CC patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression feature and prognostic values of FXYD members were identified. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism underlying the function of the FXYD family in CC. Tumor Immune Estimation Resource (TIMER) and CIBERSORT analysis were used to assess the correlations between FXYD family members and tumor immune infiltrating cells (TIICs). FXYD family members were differentially expressed in CC except for FXYD2. FXYD2, FXYD3 and FXYD4 were revealed as independent prognostic factors for recurrence, while FXYD3 and FXYD7 were identified as prognostic factors for survival according to univariate and multivariate analyses with Cox regression. GSEA revealed that FXYD family members were involved in complicated biological functions underlying cancer progression. TIMER and CIBERSORT analyses showed significant associations between FXYD family genes and TIICs. The present study comprehensively revealed the expression mode and prognostic value of FXYD members in CC, providing insights for further study of the FXYD family as potential clinical biomarkers in CC.
| S-EPMC8351680 | biostudies-literature
Project description: Not available
| S-EPMC10944899 | biostudies-literature
Project description:BackgroundColon cancer is the third most common malignant tumor in the world. Although immunotherapy has been used in cancer treatment, there is still no first-line immunotherapy method for colon cancer. Therefore, it is essential to search for potential immunotherapy targets and molecular biomarkers for early diagnosis and prognosis.MethodsIn this study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) and immune-related genes from the ImmPort database. Then we filtered genes with prognostic value and constructed an immune-related signature. Patients were classified into low- and high-risk groups, and we exerted a series of analysis between the signature and clinical phenotypes. Additionally, we used protein-protein interaction networks, gene set enrichment analysis (GSEA) and single-sample gene-set enrichment analysis (ssGSEA) to explore the underlying mechanism of this signature. Furthermore, the accuracy of this signature was verified, using two data sets from Gene Expression Omnibus (GEO).ResultsWe selected 12 immune-related genes to construct the immune-related signature. Low-risk group had a higher level of immunity compared to high-risk group. The expression level of HLA genes and checkpoint-related genes were statistically different in low- and high-risk groups. This signature showed its prognostic value in TCGA cohort and 2 GEO data sets. The signature also had strong correlation with TNM classification, stage, survival state and lymphatic invasion. The mechanism of the signature may be related to several transcription factors and CD8+ T cell in the tumor microenvironment.ConclusionIn conclusion, this immune-related signature is of great prognosis value for colon cancer and its biofunction might be correlated with HLA genes, checkpoint-related genes and high-infiltrating T cells in tumor tissues.
| S-EPMC8106397 | biostudies-literature
Project description:ObjectiveDisulfidptosis is a newly identified type of nonapoptotic programmed cell death related to mechanisms such as ferroptosis, cuproptosis, pyroptosis, and necrotic apoptosis. This study explores the role of disulfidptosis-related long non-coding RNAs (DRLs) in gastric cancer and their potential as prognostic biomarkers.MethodWe developed a prognostic model using DRL scores to classify patients based on disulfidptosis activity. We evaluated these scores for correlations with drug sensitivity, tumor microenvironment (TME) features, tumor mutational burden (TMB), and prognosis. Potential disulfidptosis-related signaling pathways were screened, identifying FRMD6-AS as a promising therapeutic target. FRMD6-AS expression was further validated using real-time fluorescent quantitative PCR (qRT-PCR).ResultsThe DRL-based prognostic model, established through univariate and multivariate Cox regression and LASSO regression analyses, outperformed traditional models in predicting prognosis. We divided samples into high-risk and low-risk groups based on DRL scores, finding that the low-risk group had a significantly higher survival rate (P < 0.05). A high-precision prediction model incorporating DRL scores, age, sex, grade, and stage showed strong predictive value and consistency with actual outcomes. High DRL scores correlated with higher TME scores and lower TMB. Key signaling axes identified were AC129507.1/(FLNA, TLN1)/FOCAL ADHESION and AC107021.2/MYH10/(TIGHT JUNCTION, VIRAL MYOCARDITIS, REGULATION OF ACTIN CYTOSKELETON). Potentially effective drugs, including BMS-754807, dabrafenib, and JQ1, were identified. FRMD6-AS emerged as a potential target for gastric cancer treatment.ConclusionsThis study developed a novel prognostic model for gastric cancer using DRLs, identifying two key signaling axes related to prognosis. JQ1 may be an effective treatment, and FRMD6-AS could be a promising therapeutic target.
| S-EPMC11913695 | biostudies-literature
Project description:Colon adenocarcinoma (COAD) is a frequently occurring and lethal cancer. Cuproptosis is an emerging type of cell death, and the underlying pathways involved in this process in COAD remain poorly understood. Transcriptomic and clinical data for COAD patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We investigated alterations in DNA and chromatin of cuproptosis-related genes (CRGs) in COAD. In order to identify predictive differentially expressed genes (DEGs) and various molecular subtypes, we used consensus cluster analysis. Through univariate, multivariate, and Lasso Cox regression analyses, four CRGs were identified. A risk prognostic model for cuproptosis characteristics was constructed based on four CRGs. This study also examined the association between the risk score and the tumor microenvironment (TME), the immune landscape, and drug sensitivity. We distinguished two unique molecular subtypes using consensus clustering analysis. We discovered that the clinical characteristics, prognosis, and TME cell infiltration characteristics of patients with multilayer CRG subtypes were all connected. The internal and external evaluations of the predicted accuracy of the prognostic model built using data derived from a cuproptosis risk score were completed at the same time. A nomogram and a clinical pathological analysis make it more useful in the field of medicine. A significant rise in immunosuppressive cells was observed in the high cuproptosis risk score group, with a correlation identified between the cuproptosis risk score and immune cell infiltration. Despite generally poor prognoses, the patients with a high cuproptosis risk but low tumor mutation burden (TMB), cancer stem cell (CSC) index, or microsatellite instability (MSI) may still benefit from immunotherapy. Furthermore, the cuproptosis risk score positively correlated with immune checkpoint gene expression. Analyzing the potential sensitivity to medications could aid in the development of clinical chemotherapy regimens and decision-making. CRGs are the subject of our in-depth study, which exposed an array of regulatory mechanisms impacting TME. In addition, we performed additional data mining into clinical features, prognosis effectiveness, and possible treatment medications. COAD's molecular pathways will be better understood, leading to more precise treatment options.
| S-EPMC11546850 | biostudies-literature
Project description:Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Previous studies have showed that ferroptosis plays an important regulatory role in the occurrence and development of tumors. Colon cancer is one of the major morbidities and causes of mortality in the world. This study used RNA-seq and colon cancer clinical data to explore the relationship between ferroptosis-related genes and colon cancer. Based on the fifteen prognostic ferroptosis-related genes, two molecular subgroups of colon cancer were identified. Surprisingly, we also found cluster2 was characterized by lower mutation burden and expression of checkpoint genes, better survival, and higher expression of NOX1. Moreover, cluster2 has fewer BRAF mutations. We also found the expression of NOX1 is related to the status of BRAF. Finally, using 15 ferroptosis-related genes from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model may be used to predict the prognosis of patients in clinics.
| S-EPMC8199073 | biostudies-literature
Project description:Tumor mutation burden (TMB) level is identified as a useful predictor in multiple tumors including colon adenocarcinoma (COAD). However, the function of TMB related genes has not been explored previously. In this study, we obtained patients' expression and clinical data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI). TMB genes were screened and subjected to differential expression analysis. Univariate Cox and LASSO analyses were utilized to construct the prognostic signature. The efficiency of the signature was tested by using a receiver operating characteristic (ROC) curve. A nomogram was further plotted to assess the overall survival (OS) time of patients with COAD. In addition, we compared the predictive performance of our signature with other four published signatures. Functional analyses indicated that patients in the low-risk group have obviously different enrichment of tumor related pathways and tumor infiltrating immune cells from that of high-risk patients. Our findings suggested that the ten genes' prognostic signature could exert undeniable prognostic functions in patients with COAD, which might provide significant clues for the development of personalized management of these patients.
| S-EPMC10214595 | biostudies-literature
Project description:Accumulating evidence revealed that autophagy played vital roles in breast cancer (BC) progression. Thus, the aim of this study was to investigate the prognostic value of autophagy-related genes (ARGs) and develop a ARG-based model to evaluate 5-year overall survival (OS) in BC patients. We acquired ARG expression profiling in a large BC cohort (N = 1007) from The Cancer Genome Atlas (TCGA) database. The correlation between ARGs and OS was confirmed by the LASSO and Cox regression analyses. A predictive model was established based on independent prognostic variables. Thus, time-dependent receiver operating curve (ROC), calibration plot, decision curve and subgroup analysis were conducted to determine the predictive performance of ARG-based model. Four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were identified using the LASSO and multivariate Cox regression analyses. A ARG-based model was constructed based on the four ARGs and two clinicopathological risk factors (age and TNM stage), dividing patients into high-risk and low-risk groups. The 5-year OS of patients in the low-risk group was higher than that in the high-risk group (P < 0.0001). Time-dependent ROC at 5 years indicated that the four ARG-based tool had better prognostic accuracy than TNM stage in the training cohort (AUC: 0.731 vs 0.640, P < 0.01) and validation cohort (AUC: 0.804 vs 0.671, P < 0.01). The mutation frequencies of the four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were 0.9%, 2.8%, 8% and 1.3%, respectively. We built and verified a novel four ARG-based nomogram, a credible approach to predict 5-year OS in BC, which can assist oncologists in determining effective therapeutic strategies.
| S-EPMC7417718 | biostudies-literature
Project description:BackgroundAs a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer.MethodsThe expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above.ResultsCompared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years.ConclusionThis study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.
| S-EPMC11495725 | biostudies-literature