A Novel Overall Survival Prediction Signature Based on Cancer Stem Cell-Related Genes in Osteosarcoma
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SUBMITTER: Xiao B
PROVIDER: S-EPMC8558458 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objectives: Ferroptosis plays vital roles in the pathogenesis of various malignant tumors. However, knowledge on roles of ferroptosis in osteosarcoma remains scarce. In the present study, a comprehensive bioinformatics analysis was performed aiming to identify ferroptosis-related genes (FRGs), construct a FRGs-based model predicting overall survival (OS), and assess the impact of these FRGs on the migration and invasion of osteosarcoma cells. Methods: Initially, data regarding differentially expressed FRGs were obtained from the GSE160881 dataset. Prognostic significance and possible biological functions of these differentially expressed FRGs were comprehensively and systematically explored adopting a series of bioinformatics methods. The impact of cystathionine β-synthase (CBS) on migration and invasion of osteosarcoma cells were assessed using transwell assays. Results: A total of 50 FRGs were differentially expressed. Four FRGs including G6PD, VEGFA, CBS, and HMOX1 were used to construct a model predicting OS in osteosarcoma patients. In the training cohort, patients with high risk had significantly poorer OS than those with low risk, which was also demonstrated in validation cohorts (GSE16091 and GSE39058). Furthermore, we established a clinically useful nomogram predicting OS using the four FRGs mentioned above. Risk scores were significantly associated with the proportion of tumor-infiltrating immune cells. Additionally, we used the Cytoscape software to identify hub FRGs, and found that TP53, HMOX1, SLC7A11, HRAS, VEGFA, and TXNRD1 were hub FRGs. By performing in vitro cell culture experiments, we demonstrated that invasion and migration capability of Saos2 and HOS cells were significantly weakened after CBS knock down. Conclusions: In conclusion, gene signatures based on four FRGs were reliable in predicting OS in patients with osteosarcoma. Findings from this study will enable a better understanding of the prognostic significance of FRGs and tumor immunity in osteosarcoma.
| S-EPMC9556449 | biostudies-literature
Project description:BackgroundOsteosarcoma is a tumour of malignant origin in children and adolescents. Recent progression indicates that it is necessary to develop new therapies to improve the patient's prognosis rather than strengthen anti-tumour chemotherapy. Researchers recently realised that cancer is a kind of disease with a metabolic disorder, and metabolic reprogramming is becoming a new cancer hallmark. Hence, our study's primary purpose is to explore the value of genes related to osteosarcoma metabolism.MethodsFrom public databases, three osteosarcoma datasets with adequate clinical information were obtained. Besides, the IMvigor dataset through the 'IMvigor' package as a supplement was downloaded, the metabolic-related genes were identified, and these genes were used to construct the metabolic-related gene pairs (MRGP). Based on the prognosis-related MRGP, two molecular subtypes were identified. There are significant differences in the metabolic characteristics between the two molecular subtypes. Subsequently, the MRGP signature is constructed using the least absolute shrinkage and selection operator regression method. Finally, use SubMap analysis to evaluate the response of patients in the MRPG signature group to immunotherapy.ResultsThe MRGP signature can reliably predict overall survival in patients with osteosarcoma. The MRGP signature is also associated with osteosarcoma patients' metastatic status and can be used for subsequent risk classification of metastatic patients. The immunotherapy is more likely to benefit the patients in the MRGP low-risk group.ConclusionMetabolic-related gene pairs signature can assess the prognosis of patients with osteosarcoma.
| S-EPMC8267140 | biostudies-literature
Project description:ObjectiveOvarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598-4 cell line and how its genes are associated with ovarian cancer prognosis.MethodsWe sequenced and annotated the eccDNA by Circle_seq of the OV cell line UACC-1598-4. To acquire the amplified genes of OV on eccDNA, the annotated eccDNA genes were intersected with the overexpression genes of OV in TCGA. Univariate Cox regression was used to find the genes on eccDNA that were linked to OV prognosis. The least absolute shrinkage and selection operator (LASSO) and cox regression models were used to create the OV prognostic model, as well as the receiver operating characteristic curve (ROC) curve and nomogram of the prediction model. By applying the median value of the risk score, the samples were separated into high-risk and low-risk groups, and the differences in immune infiltration between the two groups were examined using ssGSEA.ResultsEccDNA in UACC-1598-4 has a length of 0-2000 bp, and some of them include the whole genes or gene fragments. These eccDNA originated from various parts of chromosomes, especially enriched in repeatmasker, introns, and coding regions. They were annotated with 2188 genes by Circle_seq. Notably, the TCGA database revealed that a total of 198 of these eccDNA genes were overexpressed in OV (p < 0.05). They were mostly enriched in pathways associated with cell adhesion, ECM receptors, and actin cytoskeleton. Univariate Cox analysis showed 13 genes associated with OV prognosis. LASSO and Cox regression analysis were used to create a risk model based on remained 9 genes. In both the training (TCGA database) and validation (International Cancer Genome Consortium, ICGC) cohorts, a 9-gene signature could successfully discriminate high-risk individuals (all p < 0.01). Immune infiltration differed significantly between the high-risk and low-risk groups. The model's area under the ROC curve was 0.67, and a nomograph was created to assist clinician.ConclusionEccDNA is found in UACC-1598-4, and part of its genes linked to OV prognosis. Patients with OV may be efficiently evaluated using a prognostic model based on eccDNA genes, including SLC7A1, NTN1, ADORA1, PADI2, SULT2B1, LINC00665, CILP2, EFNA5, TOMM.
| S-EPMC10278296 | biostudies-literature
Project description:Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.
| S-EPMC7136791 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001 in the TCGA cohort and P = 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.
| S-EPMC7378635 | biostudies-literature
Project description:IntroductionBreast cancer is the most common malignant tumor in women worldwide. However, advanced multidisciplinary therapy cannot rescue the mortality of high-risk breast cancer metastasis. Ferroptosis is a newly discovered form of regulating cell death that related to cancer treatment, especially in eradicating aggressive malignancies that are resistant to traditional therapies. However, the prognostic value of ferroptosis-related gene in breast cancer remains unknown.Materials and methodsIn this study, a total of 1,057 breast cancer RNA expression data with clinical and follow-up information were downloaded from the TCGA cohort, multivariate Cox regression was used to construct the 11-gene prognostic ferroptosis-related gene signature. The breast cancer patients from the GEO cohort were used for validation. The expression levels of core prognostic genes were also verified in erastin-treated breast cancer cell lines by real-time polymerase chain action (PCR).Results and discussionOur results showed that 78% ferroptosis-related genes were differentially expressed between breast cancer tumor tissue and adjacent non-tumorous tissues, including 29 of them which were significantly correlated with OS in the univariate Cox regression analysis. Patients were divided into high-risk group and low-risk group by the 11-gene signature. Patients with high-risk scores had a higher probability of death earlier than the low-risk group both in the TCGA construction cohort and in the GEO validation cohort (all P < 0.001). Meanwhile, the risk score was proved to be an independent predictor for OS in both univariate and multivariate Cox regression analyses (HR > 1, P < 0.01). The predictive efficacy of the prognostic signature for OS was further verified by the time-dependent ROC curves. Moreover, we also enriched many immune-related biological processes in later functional analysis; the immune status showed a statistical difference between the two risk groups. In addition, the differences in expression levels of 11 core prognostic genes were examined in ferroptosis inducer-treated breast cancer cell lines.ConclusionIn conclusion, a novel ferroptosis-related gene model can be used for prognostic prediction in breast cancer. New ferroptosis-related genes may be used for breast cancer targeting therapy in the future.
| S-EPMC8247647 | biostudies-literature
Project description:IntroductionGlioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients.MethodsIn this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM.ResultsDepending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups.ConclusionThe 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.
| S-EPMC7847336 | biostudies-literature
Project description:Osteosarcoma (OS) is a common malignant primary tumor of skeleton, especially in children and adolescents, characterized by high lung metastasis rate. Apoptosis has been studied in various tumors, while the prognostic role of apoptosis-related genes in OS has been seldom studied. Three OS related datasets were downloaded from Gene Expression Omnibus (GEO) database. Univariate Cox and LASSO Cox regression analysis identified optimal genes, which were used for building prognostic Risk score. Subsequent multivariate Cox regression analysis and Kaplan-Meier survival analysis determined the independent prognostic factors for OS. The immune cell infiltration was analyzed in CIBERSORT. Basing on 680 apoptosis-related genes, the OS patients could be divided into 2 clusters with significantly different overall survival. Among which, 6 optimal genes were identified to construct Risk score. In both training set (GSE21257) and validation set (meta-GEO dataset), high risk OS patients had significantly worse overall survival compared with the low risk patients. Besides, high Risk score was an independent poor prognostic factor for OS with various ages or genders. Three immune cells were differentially infiltrated between high and low risk OS patients. In conclusion, a six-gene (TERT, TRAP1, DNM1L, BAG5, PLEKHF1 and PPP3CB) based prognostic Risk score signature is probably conducive to distinguish different prognosis of OS patients.
| S-EPMC9134960 | biostudies-literature
Project description:We downloaded the mRNA expression profiles of patients with LUAD and corresponding clinical data from The Cancer Genome Atlas (TCGA) database and used the Least Absolute Shrinkage and Selection Operator Cox regression model to construct a multigene signature in the TCGA cohort, which was validated with patient data from the GEO cohort. Results showed differences in the expression levels of 120 necroptosis-related genes between normal and tumor tissues. An eight-gene signature (CYLD, FADD, H2AX, RBCK1, PPIA, PPID, VDAC1, and VDAC2) was constructed through univariate Cox regression, and patients were divided into two risk groups. The overall survival of patients in the high-risk group was significantly lower than of the patients in the low-risk group in the TCGA and GEO cohorts, indicating that the signature has a good predictive effect. The time-ROC curves revealed that the signature had a reliable predictive role in both the TCGA and GEO cohorts. Enrichment analysis showed that differential genes in the risk subgroups were associated with tumor immunity and antitumor drug sensitivity. We then constructed an mRNA-miRNA-lncRNA regulatory network, which identified lncRNA AL590666. 2/let-7c-5p/PPIA as a regulatory axis for LUAD. Real-time quantitative PCR (RT-qPCR) was used to validate the expression of the 8-gene signature. In conclusion, necroptosis-related genes are important factors for predicting the prognosis of LUAD and potential therapeutic targets.
| S-EPMC10504370 | biostudies-literature
Project description:Cuproptosis is a copper-dependent model of cell death involved in tumor genesis and progression. Its roles in uterine corpus endometrial carcinoma (UCEC) remains elusive. Here, we aimed to explore the expression and prognostic values of cuprotosis-related genes (CRGs) in UCEC. Expression profiles and clinical data of UCEC were downloaded from The Cancer Genome Atlas (TCGA), and randomly divided into testing or training cohort (1:1 ratio). The CRG signature was identified by LASSO regression analysis. The differentially expressed genes and their functional enrichment analysis were performed by the "limma" R package and Metascape, respectively. The immunocytes infiltration was measured by TIMER, and "GSVA" R package. In total, seven differentially expressed prognostic genes of CRGs in UCEC were identified, and four genes (GLS, CDKN2A, PC, and SUCLG1) were selected to construct a predictive model in training cohort. UCEC patients from training and testing cohorts were further divided into high- or low-risk groups according to the median risk score. High-risk group favored poor prognosis compared to low-risk group. Functional enrichment analysis revealed this CRG signature were got involved in the process of cell-cell adhesion and immune activities (e.g., IL-1 signaling pathway, cellular response to cytokine stimulus). Further analyses revealed there were significant differences between high- and low-risk patients regarding immunocytes infiltration, chemokines, and chemokine receptors. Finally, the expression and biological functions of identified CRGs were confirmed by UCEC samples and experimental methods in vitro. In summary, the CRG signature was significantly correlated with patients' overall survival, which could provide insights into the diagnosis and prognosis prediction for UCEC.
| S-EPMC10073764 | biostudies-literature