Robust prognostic gene expression signatures in bladder cancer and lung adenocarcinoma depend on cell cycle related genes.
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ABSTRACT:
SUBMITTER: Dancik GM
PROVIDER: S-EPMC3898982 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo screen lung adenocarcinoma (LUAC)-specific cell-cycle-related genes (CCRGs) and develop a prognostic signature for patients with LUAC.MethodsThe GSE68465, GSE42127, and GSE30219 data sets were downloaded from the GEO database. Single-sample gene set enrichment analysis was used to calculate the cell cycle enrichment of each sample in GSE68465 to identify CCRGs in LUAC. The differential CCRGs compared with LUAC data from The Cancer Genome Atlas were determined. The genetic data from GSE68465 were divided into an internal training group and a test group at a ratio of 1:1, and GSE42127 and GSE30219 were defined as external test groups. In addition, we combined LASSO (least absolute shrinkage and selection operator) and Cox regression analysis with the clinical information of the internal training group to construct a CCRG risk scoring model. Samples were divided into high- and low-risk groups according to the resulting risk values, and internal and external test sets were used to prove the validity of the signature. A nomogram evaluation model was used to predict prognosis. The CPTAC and HPA databases were chosen to verify the protein expression of CCRGs.ResultsWe identified 10 LUAC-specific CCRGs (PKMYT1, ETF1, ECT2, BUB1B, RECQL4, TFRC, COCH, TUBB2B, PITX1, and CDC6) and constructed a model using the internal training group. Based on this model, LUAC patients were divided into high- and low-risk groups for further validation. Time-dependent receiver operating characteristic and Cox regression analyses suggested that the signature could precisely predict the prognosis of LUAC patients. Results obtained with CPTAC, HPA, and IHC supported significant dysregulation of these CCRGs in LUAC tissues.ConclusionThis prognostic prediction signature based on CCRGs could help to evaluate the prognosis of LUAC patients. The 10 LUAC-specific CCRGs could be used as prognostic markers of LUAC.
| S-EPMC8044954 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD), one of the most common pathological subtypes in lung cancer, has been of concern because it is the leading cause of cancer-related deaths. Due to its poor prognosis, to identify a prognostic biomarker, this study performed an integrative analysis to screen curial RNAs and discuss their cross-talks. The messenger RNA (mRNA) profiles were primarily screened using robust rank aggregation (RRA) through several datasets, and these deregulated genes showed important roles in multiple biological pathways, especially for cell cycle and oocyte meiosis. Then, 31 candidate genes were obtained via integrating 12 algorithms, and 16 hub genes (containing homologous genes) were further screened according to the potential prognostic values. These hub genes were used to search their regulators and biological-related microRNAs (miRNAs). In this way, 10 miRNAs were identified as candidate small RNAs associated with LUAD, and then miRNA-related long non-coding RNAs (lncRNAs) were further obtained. In-depth analysis showed that 4 hub mRNAs, 2 miRNAs, and 2 lncRNAs were potential crucial RNAs in the occurrence and development of cancer, and a competing endogenous RNA (ceRNA) network was then constructed. Finally, we identified CCNA2/MKI67/KIF11:miR-30a-5p:VPS9D1-AS1 axis-related cell cycle as a prognostic biomarker, which provided RNA cross-talks among mRNAs and non-coding RNAs (ncRNAs), especially at the multiple isomiR levels that further complicated the coding-non-coding RNA regulatory network. Our findings provide insight into complex cross-talks among diverse RNAs particularly involved in isomiRs, which will enrich our understanding of mRNA-ncRNA interactions in coding-non-coding RNA regulatory networks and their roles in tumorigenesis.
| S-EPMC8853726 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in morphology, biochemistry, and genetics, and has played a vital role in cancer biology. This study aimed to identify a ferroptosis-related gene signature associated with LUAD prognosis.MethodsDataset TCGA-LUAD which came from the TCGA portal was taken as the training cohort. GSE72094 and GSE68465 from the GEO database were treated as validation cohorts. Two hundred fifty-nine ferroptosis-related genes were retrieved from the FerrDb database. In the training cohort, Kaplan-Meier and univariate Cox analyses were conducted for preliminary screening of ferroptosis-related genes with potential prognostic capacity. These genes then entered into the LASSO Cox regression model, constructing a gene signature. The latter was then evaluated in the training and validation cohorts via Kaplan-Meier, Cox, and ROC analyses. In addition, the correlations between risk score and autophagy were examined by Pearson correlation coefficient. The analyses of GSEA and immune infiltrating were performed for better studying the function annotation of the gene signature and the character of each kind of immune cells played in the tumor microenvironment.ResultsA 15-gene signature was found from the training cohort and validated by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in LUAD. Moreover, the ROC analysis was conducted, confirming a strong predictive ability that this signature owned for LUAD prognosis. One hundred fifty-one of 222 (68.01%) autophagy-related genes were discovered significantly correlated with risk scores. Analyses of GSEA and immune infiltration exhibited in detail the specific pathways that associate with the 15-gene signature and identified the crucial roles of resting mast cells and resting dendritic cells owned in the prognosis of the 15-gene signature.ConclusionIn this present study, a novel ferroptosis-related 15-gene signature (RELA, ACSL3, YWHAE, EIF2S1, CISD1, DDIT4, RRM2, PANX1, TLR4, ARNTL, LPIN1, HERPUD1, NCOA4, PEBP1, and GLS2) was built. It could accurately predict the prognosis of LUAD and was related to resting mast cells and resting dendritic cells, which provide potential for the personalized outcome prediction and the development of new therapies in LUAD population.
| S-EPMC8264775 | biostudies-literature
Project description:BackgroundCancer stem cells (CSCs) refer to cells with self-renewal capability in tumors. CSCs play important roles in proliferation, metastasis, recurrence, and tumor heterogeneity. This study aimed to identify immune-related gene-prognostic models based on stemness index (mRNAsi) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively.MethodsX-tile software was used to determine the best cutoff value of survival data in LUAD and LUSC based on mRNAsi. Tumor purity and the scores of infiltrating stromal and immune cells in lung cancer tissues were predicted with ESTIMATE R package. Differentially expressed immune-related genes (DEIRGs) between higher- and lower-mRNAsi subtypes were used to construct prognostic models.ResultsmRNAsi was negatively associated with StromalScore, ImmuneScore, and ESTIMATEScore, and was positively associated with tumor purity. LUAD and LUSC samples were divided into higher- and lower-mRNAsi groups with X-title software. The distribution of immune cells was significantly different between higher- and lower-mRNAsi groups in LUAD and LUSC. DEIRGs between those two groups in LUAD and LUSC were enriched in multiple cancer- or immune-related pathways. The network between transcriptional factors (TFs) and DEIRGs revealed potential mechanisms of DEIRGs in LUAD and LUSC. The eight-gene-signature prognostic model (ANGPTL5, CD1B, CD1E, CNTFR, CTSG, EDN3, IL12B, and IL2)-based high- and low-risk groups were significantly related to overall survival (OS), tumor microenvironment (TME) immune cells, and clinical characteristics in LUAD. The five-gene-signature prognostic model (CCL1, KLRC3, KLRC4, CCL23, and KLRC1)-based high- and low-risk groups were significantly related to OS, TME immune cells, and clinical characteristics in LUSC. These two prognostic models were tested as good ones with principal components analysis (PCA) and univariate and multivariate analyses. Tumor T stage, pathological stage, or metastasis status were significantly correlated with DEIRGs contained in prognostic models of LUAD and LUSC.ConclusionCancer stemness was not only an important biological process in cancer progression but also might affect TME immune cell infiltration in LUAD and LUSC. The mRNAsi-related immune genes could be potential biomarkers of LUAD and LUSC. Evaluation of integrative characterization of multiple immune-related genes and pathways could help to understand the association between cancer stemness and tumor microenvironment in lung cancer.
| S-EPMC8567176 | biostudies-literature
Project description:In recent years, genes associated with N6-methyladenosine (m6A) modification were found to participate in modulation of multiple tumor biological processes. Concomitantly, the significantly complicated dual effects of tumor microenvironment have been observed on cancer progression. The present study aims to investigate m6A-related immune genes (m6AIGs) for their signatures and prognostic values in bladder cancer (BC). Out of 2856 differentially expressed genes (DEGs) of BC, a total of 85 genes were obtained following intersection of DEGs, immune genes and m6A-related genes. The results of multivariate Cox regression analysis illustrated four genes (BGN, GRK5, IL32, and SREBF1) were significantly associated with the prognosis of BC patients. The BC samples were divided into two types based on the consensus clustering, and the principal component analysis demonstrated a separation between them. It was found that high expression of BGN and GRK5 were linked with advanced T and N stage, and the expression of SREBF1 in early T stage was higher than that in advanced T stage. Subsequently, the nomogram to predict 3- and 5-year survival probability of BC patients was developed and calibrated. GSEA analysis for risk subgroups showed WNT and TGF-beta signaling pathways were involved in regulation of BC progression in high risk level group. In the low risk level group, cytosolic DNA-Sensing cGAS-STING and RIG-I-like receptors signaling pathways were found to be correlated with BC development. These findings provide a novel insight on studies for BC progression.
| S-EPMC8806594 | 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:Lung adenocarcinoma (LUAD) is characterized by high infiltration and rapid growth. The function of the stem cell population is to control and maintain cell regeneration. Therefore, it is necessary to study the prognostic value of stem cell-related genes in LUAD. Signature genes were screened out from 166 stem cell-related genes according to the least absolute shrinkage operator (LASSO) and subsequently multivariate Cox regression analysis, and then established risk model. Immune infiltration and nomogram model were used to evaluate the clinical efficacy of signature. A signature consisting of 10 genes was used to dichotomize the LUAD patients into two groups (cutoff, 1.314), and then validated in GSE20319 and GSE42127. There was a significant correlation between signature and clinical characteristics. Patients with high-risk had a shorter overall survival. Furthermore, significant differences were found in multiple immune cells between the high-risk group and low-risk group. A high correlation was also reflected between signature and immune infiltration. What's more, the signature could effectively predict the efficacy of chemotherapy in patients with LUAD, and a nomogram based on signature might accurately predict the prognosis of patients with LUAD. The signature-based of stem cell-related genes might be contributed to predicting prognosis of patients with LUAD.
| S-EPMC7814011 | biostudies-literature
Project description:Background:Lung adenocarcinoma (LUAD) is the main subtype of non-small cell lung cancer with a low survival prognosis. We aimed to generate a prognostic model for the postoperative recurrence of LUAD. Methods:The methylated DNA data of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA). The differentially methylated genes were identified and protein-protein interacting network was constructed, with which prognostic signature of this cancer was generated. Survival and functional pathways analysis w used to evaluate the clustering ability of the prognostic signature. Results:We identified 151 differentially methylated genes related to relapse-free survival of patients with LUAD. Nine hub genes were identified in PPI network, with which 4 gene pair signature was selected as prognostic signature. The potential functions of 6 genes (JDP2, SERPINA5, PLG, SEMG2, RFX5, and POLR3B) in the 4-gene pair signature were enriched in intracellular protein synthesis and transportation. Conclusion:The four gene pair signature can predict the prognosis of patients with stage I LUAD. Our study provides a reference for patients with postoperative adjuvant therapy.
| S-EPMC5909272 | biostudies-literature
Project description:BackgroundThe incidence of stage I and stage II lung adenocarcinoma (LUAD) is likely to increase with the introduction of annual screening programs for high-risk individuals. We aimed to identify a reliable prognostic signature with immune-related genes that can predict prognosis and help making individualized management for patients with early-stage LUAD.MethodsThe public LUAD cohorts were obtained from the large-scale databases including 4 microarray data sets from the Gene Expression Omnibus (GEO) and 1 RNA-seq data set from The Cancer Genome Atlas (TCGA) LUAD cohort. Only early-stage patients with clinical information were included. Cox proportional hazards regression model was performed to identify the candidate prognostic genes in GSE30219, GSE31210 and GSE50081 (training set). The prognostic signature was developed using the overlapped prognostic genes based on a risk score method. Kaplan-Meier curve with log-rank test and time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic value and performance of this signature, respectively. Furthermore, the robustness of this prognostic signature was further validated in TCGA-LUAD and GSE72094 cohorts.ResultsA prognostic immune signature consisting of 21 immune-related genes was constructed using the training set. The prognostic signature significantly stratified patients into high- and low-risk groups in terms of overall survival (OS) in training data set, including GSE30219 (HR = 4.31, 95% CI 2.29-8.11; P = 6.16E-06), GSE31210 (HR = 11.91, 95% CI 4.15-34.19; P = 4.10E-06), GSE50081 (HR = 3.63, 95% CI 1.90-6.95; P = 9.95E-05), the combined data set (HR = 3.15, 95% CI 1.98-5.02; P = 1.26E-06) and the validation data set, including TCGA-LUAD (HR = 2.16, 95% CI 1.49-3.13; P = 4.54E-05) and GSE72094 (HR = 2.95, 95% CI 1.86-4.70; P = 4.79E-06). Multivariate cox regression analysis demonstrated that the 21-gene signature could serve as an independent prognostic factor for OS after adjusting for other clinical factors. ROC curves revealed that the immune signature achieved good performance in predicting OS for early-stage LUAD. Several biological processes, including regulation of immune effector process, were enriched in the immune signature. Moreover, the combination of the signature with tumor stage showed more precise classification for prognosis prediction and treatment design.ConclusionsOur study proposed a robust immune-related prognostic signature for estimating overall survival in early-stage LUAD, which may be contributed to make more accurate survival risk stratification and individualized clinical management for patients with early-stage LUAD.
| S-EPMC7542703 | biostudies-literature
Project description:BackgroundLung adenocarcinoma is the most common lung cancer subtype and accounts for the highest proportion of cancer-related deaths. The tumor microenvironment influences prognostic outcomes in lung adenocarcinoma (LUAD).Materials and methodsWe used the ESTIMATE algorithm (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) to investigate the role of microenvironment-related genes and stromal cells in lung adenocarcinoma prognosis. This analysis was done on lung adenocarcinoma cases from The Cancer Genome Atlas (TCGA). The cases were divided into high and low groups on the basis of immune and stromal scores, respectively.ResultsThere were close correlations between immune scores with prognosis and disease stage. There were 367 differentially expressed genes. Combining the Gene Expression Omnibus (GEO) database, we found 14 prognosis-related genes.ResultsThere were close correlations between immune scores with prognosis and disease stage. There were 367 differentially expressed genes. Combining the Gene Expression Omnibus (GEO) database, we found 14 prognosis-related genes. Results. Based on the enrichment levels of the immune cell types, we clustered LUAD into Immunity_H and Immunity_L subtypes. Most of these genes were upregulated in Immunity_H subtype. Finally, using the Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, most of the proteins corresponding to prognostic genes were verified to be differentially expressed between the tumor and normal groups.ConclusionsThe key genes identified in this study are involved in molecular mechanisms of LUAD.
| S-EPMC9411923 | biostudies-literature