Dataset Information

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

ABSTRACT: Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan-Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

SUBMITTER: Tan J

PROVIDER: S-EPMC7867449 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

Tan Jianye J Liang Haofeng H Yang Bingsheng B Zhu Shuang S Wu Guofeng G Li Lutao L Liu Zhengwei Z Li Lin L Qi Weizhong W Li Sijing S Lin Lijun L

Journal of oncology 20210130

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognos ...[more]

PMID: 33564309

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Project description:BackgroundGlycolytic metabolic pathway has been confirmed to play a vital role in the proliferation, survival, and migration of malignant tumors, but the relationship between glycolytic pathway-related genes and osteosarcoma (OS) metastasis and prognosis remain unclear.MethodsWe performed Gene set enrichment analysis (GSEA) on the osteosarcoma dataset in the TARGET database to explore differences in glycolysis-related pathway gene sets between primary osteosarcoma (without other organ metastases) and metastatic osteosarcoma patient samples, as well as glycolytic pathway gene set gene difference analysis. Then, we extracted OS data from the TCGA database and used Cox proportional risk regression to identify prognosis-associated glycolytic genes to establish a risk model. Further, the validity of the risk model was confirmed using the GEO database dataset. Finally, we further screened OS metastasis-related genes based on machine learning. We selected the genes with the highest clinical metastasis-related importance as representative genes for in vitro experimental validation.ResultsUsing the TARGET osteosarcoma dataset, we identified 5 glycolysis-related pathway gene sets that were significantly different in metastatic and non-metastatic osteosarcoma patient samples and identified 29 prognostically relevant genes. Next, we used multivariate Cox regression to determine the inclusion of 13 genes (ADH5, DCN, G6PD, etc.) to construct a prognostic risk score model to predict 1- (AUC=0.959), 3- (AUC=0.899), and 5-year (AUC=0.895) survival under the curve. Ultimately, the KM curves pooled into the datasets GSE21257 and GSE39055 also confirmed the validity of the prognostic risk model, with a statistically significant difference in overall survival between the low- and high-risk groups (P<0.05). In addition, machine learning identified INSR as the gene with the highest importance for OS metastasis, and the transwell assay verified that INSR significantly promoted OS cell metastasis.ConclusionsA risk model based on seven glycolytic genes (INSR, FAM162A, GLCE, ADH5, G6PD, SDC3, HS2ST1) can effectively evaluate the prognosis of osteosarcoma, and in vitro experiments also confirmed the important role of INSR in promoting OS migration.

Project description:BACKGROUND:Gastric cancer (GC) is a prevalent malignant cancer of digestive system. To identify key genes in GC, mRNA microarray GSE27342, GSE29272, and GSE33335 were downloaded from GEO database. METHODS:Differentially expressed genes (DEGs) were obtained using GEO2R. DAVID database was used to analyze function and pathways enrichment of DEGs. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape software. Then, the influence of hub genes on overall survival (OS) was performed by the Kaplan-Meier plotter online tool. Module analysis of the PPI network was performed using MCODE. Additionally, potential stem loop miRNAs of hub genes were predicted by miRecords and screened by TCGA dataset. Transcription factors (TFs) of hub genes were detected by NetworkAnalyst. RESULTS:In total, 67 DEGs were identified; upregulated DEGs were mainly enriched in biological process (BP) related to angiogenesis and extracellular matrix organization and the downregulated DEGs were mainly enriched in BP related to ion transport and response to bacterium. KEGG pathways analysis showed that the upregulated DEGs were enriched in ECM-receptor interaction and the downregulated DEGs were enriched in gastric acid secretion. A PPI network of DEGs was constructed, consisting of 43 nodes and 87 edges. Twelve genes were considered as hub genes owing to high degrees in the network. Hsa-miR-29c, hsa-miR-30c, hsa-miR-335, hsa-miR-33b, and hsa-miR-101 might play a crucial role in hub genes regulation. In addition, the transcription factors-hub genes pairs were displayed with 182 edges and 102 nodes. The high expression of 7 out of 12 hub genes was associated with worse OS, including COL4A1, VCAN, THBS2, TIMP1, COL1A2, SERPINH1, and COL6A3. CONCLUSIONS:The miRNA and TFs regulation network of hub genes in GC may promote understanding of the molecular mechanisms underlying the development of gastric cancer and provide potential targets for GC diagnosis and treatment.

Project description:BackgroundCopper is an indispensably mineral element involved in various metabolic processes and functions in the active sites of many metalloproteins. Copper dysregulation is associated with cancers such as osteosarcoma (OS), the most common primary bone malignancy with invasiveness and metastasis. However, the causality between cuproptosis and OS remains elusive. We aim to identify cuproptosis-related long non-coding RNAs (lncRNAs) for osteosarcomatous prognosis, immune microenvironment response, and immunotherapy.MethodsThe Person correlation and differential expression analysis were used to identify differentially expressed cuproptosis-related lncRNAs (CRLs). The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct the CRL signature. The Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) curve, internal validation, independent prognostic analysis, and nomograph were used to evaluate the prognostic value. The functional enrichment, tumor microenvironment, immunotherapy and chemotherapy response between the two distinct groups were further explored using a series of algorithms. The expression of signature CRLs was verified by real-time quantitative polymerase chain reaction (RT-qPCR) in OS cell lines.ResultsA novel CRL signature consisting of four CRLs were successfully identified. The K-M survival analysis indicated that the OS patients in the low-risk groups had a better prognosis than that in the high-risk group. Then, the ROC curve and subgroup survival analysis confirmed the prognostic evaluation performance of the signature. Equally, the independent prognostic analysis demonstrated that the CRL signature was an independently predicted factor for OS. Friends analysis determined the hub genes that played a critical role in differentially expressed genes between two distinct risk groups. In addition, the risk score was related to immunity status, immunotherapy response, and chemotherapeutic drug sensitivity. Finally, the expression of these signature CRLs detected by RT-qPCR was consistent with the bioinformatic analysis results.ConclusionIn summary, our study confirmed that the novel CRL signature could effectively evaluate prognosis, tumor immune microenvironment, and immunotherapy response in OS. It may benefit for clinical decision-making and provide new insights for personalized therapeutics.

Project description:BackgroundThe liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC.MethodsThe publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein-protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells.ResultsWe identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1.ConclusionWe identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.

Dataset Information

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

Publications

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

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