Expression and Prognostic Value of MCM Family Genes in Osteosarcoma.
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ABSTRACT:
SUBMITTER: Zhou J
PROVIDER: S-EPMC8257954 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein-protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.
| S-EPMC8943205 | biostudies-literature
Project description:BackgroundThe Perilipin (PLIN) family of genes were previously shown to be involved in the formation and degradation of Lipid Droplets (LDs). In addition, they may play important roles in the development and progression of breast cancer. However, the prognostic value of PLIN family members in breast cancer patients remains unclear.MethodsMutations and copy number alterations of PLIN family genes in breast cancer were examined using the cBioportal for Cancer Genomics. In addition, the expression patterns of PLIN family genes were explored using the UCSC Xena online tool. Finally, the Kaplan-Meier Plotter was used to investigate the prognostic value of PLIN family genes in breast cancer.ResultsThe findings revealed a low frequency of genetic alterations and amplification was the most frequent change in the PLIN family genes. Additionally, there was an increase in the expression of Perilipin 3 (PLIN3) in breast cancer tissues compared to normal breast tissues. However, expression of the other genes in the PLIN family was significantly lower in breast cancer tissues compared to normal breast tissues. Moreover, there was an increase in the expression levels of Perilipin 1 (PLIN1), PLIN3, Perilipin 4 (PLIN4) and Perilipin 5 (PLIN5) in the luminal A and luminal B subgroups. On the other hand, the expression of Perilipin 2 (PLIN2) was elevated in the human epidermal growth factor receptor 2 (HER2) positive and basal-like subgroups. Furthermore, Kaplan-Meier Plotter analysis demonstrated that high expression of PLIN1 might predict a longer Overall Survival (OS) in patients with breast cancer while overexpression of PLIN2 indicated poor OS of breast cancer patients.ConclusionThe findings from this study indicated that genes in the PLIN family were aberrantly expressed in breast cancer and may serve as novel therapeutic targets as well as prognostic biomarkers for the disease.
| S-EPMC8205812 | biostudies-literature
Project description:BackgroundAbnormal regulation of the NOTCH signaling pathway in prostate cancer (PCa) can promote tumorigenesis, progression, and T cell exhaustion. However, there has not been a comprehensive analysis of NOTCH family genes (NOTCHs) as potential therapeutic targets and prognostic biomarkers for PCa patients.MethodsNOTCHs expressions in various types of cancer tissues and normal adjacent tissues in the TIMER and UALCAN database were screened. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were applied to validate the expression pattern of NOTCHs in clinical samples. The relationships of NOTCHs expression and clinicopathologic parameters or disease-free survival (DFS) were evaluated via GEPIA2 and UALCAN. A proteins network was built using STRING and GeneMANIA. Additionally, NOTCHs mutation status was analyzed by cBioportal. Finally, we used GDSC and TIMER to investigate NOTCH signaling-related drugs and immune cell infiltration.ResultsThe transcriptional levels of NOTCH1 and NOTCH4 in PCa tissues were significantly lower than in normal tissues, which was further validated in clinical patients' tissue samples. Furthermore, NOTCH1, NOTCH3, and NOTCH4 expressions in PCa were associated with worse DFS. Interestingly, there was a significant positive correlation between NOTCHs and androgen receptor (AR), but not with AR-related genes (KLK3 and TMPRSS2). Finally, we found that NOTCHs expressions were remarkably associated with infiltration of B cells, CD8+/CD4+ T cells, macrophages, neutrophils, and dendritic cells, which indicated that NOTCHs mutation status might be a potential therapeutic target for -tinib antineoplastic drugs.ConclusionsThe expression and mutation of NOTCH1-4 in PCa were associated with disease progression, prognosis, immune cell infiltration, and drug sensitivity.
| S-EPMC9177255 | biostudies-literature
Project description:Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.
| S-EPMC11364764 | biostudies-literature
Project description:BACKGROUND:The aim of this study was to investigate the potential prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy. METHODS:Kaplan-Meier survival analysis method with log-rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin-4 family genes expression and PDAC patients overall survival time. Joint-effect survival analysis and stratified survival analysis were carried out to assess the prognosis prediction value of prognosis-related gene. Nomogram was constructed for the individualized prognosis prediction. In addition, we had used the gene set enrichment analysis and genome-wide co-expression analysis to further explore the potential mechanism. RESULTS:KIF21A expression level was significantly associated with PDAC patient clinical prognosis outcome and patient with a high expression of KIF21A would have a shorter overall survival time. The prognosis prediction significance of KIF21A was well validated by the joint-effect survival analysis, stratified survival analysis, and nomogram. Meanwhile, the gene set enrichment analysis and genome-wide co-expression analysis revealed that KIF21A might involve in DNA damage and repair, transcription and translation process, post-translation protein modification, cell cycle, carcinogensis genes and pathways. CONCLUSIONS:Our current research demonstrated that KIF21A could serve as a potential prognostic biomarker for patient with early-stage PDAC after pancreaticoduodenectomy.
| S-EPMC6826000 | biostudies-literature
Project description:BackgroundSignal transducer and activator of transcription (STAT) proteins are well-known transcription factors that play an important role in the progression of cancer. However, the association between STAT family genes and hepatocellular carcinoma (HCC) remains unclear. This study investigates the expression level, the prognostic value and the potential mechanism of STAT family genes in HCC.MethodsData from 365 HCC patients in The Cancer Genome Atlas (TCGA) database and 241 HCC patients in the Gene Expression Omnibus (GEO) database were used to investigate the diagnostic and prognostic values of STAT genes by survival analysis and nomogram. Gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of the STAT genes in the development of HCC.ResultsOur results showed that STAT4/5B mRNA expression levels in HCC tissues were lower than those in normal tissues. Importantly, our results indicated that high expression of STAT5A, STAT5B and STAT6 was associated with better overall survival in HCC patients. Joint effects analysis of STAT5A, STAT5B and STAT6 suggested that the prognosis difference for any combination of genes was more significant than that for any individual gene. Then, we developed a risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The ROC and calibration curves showed good performance in survival prediction in both the TCGA and the GEO databases. GSEA suggested that high expression of STAT5A, STAT5B and STAT6 were involved in immune-related biological processes, drug metabolism cytochrome P450, JAK-STAT signalling pathway, and PPAR signalling pathways.ConclusionOur data suggest that STAT5A, STAT5B and STAT6 expression may be potential prognostic markers of HCC and, in combination, have a better predictive value for HCC prognosis.
| S-EPMC6731967 | biostudies-literature
Project description:BackgroundEsophageal cancer (EC) is one of the most common human malignant tumors worldwide. Chromobox (CBX) family proteins are significant components of epigenetic regulatory complexes. It is reported that CBXs play critical roles in the oncogenesis and development of various tumors. Nonetheless, their functions and specific roles in EC remain vague and obscure.Methods and materialsWe used multiple bioinformatics tools, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, Kaplan-Meier plotter, cBioPortal, Metascape, TIMER2 and TISIDB, to investigate the expression profile, gene alterations and prognostic roles of CBX family proteins, as well as their association with clinicopathologic parameters, immune cells and immune regulators. In addition, RT-qPCR, Western blot, CCK8, colony formation, wound healing and transwell assays were performed to investigate the biological functions of CBX3 in EC cells.ResultsCBX3 and CBX5 were overexpressed in EC compared to normal tissues. Survival analysis revealed that high expression of CBX1 predicted worse disease-free survival (DFS) in EC patients. Functionally, CBXs might participate in mismatch repair, spliceosome, cell cycle, the Fanconi anemia pathway, tight junction, the mRNA surveillance pathway and the Hippo signaling pathway in EC development. Furthermore, CBXs were related to distinct immune cells infiltration and immune regulators. Additionally, depletion of CBX3 inhibited the proliferation, migration and invasion abilities of EC cells.ConclusionsOur study comprehensively investigated the expression pattern, prognostic value, and gene alterations of CBXs in EC, as well as their relationships with clinicopathologic variables, immune cells infiltration and immune regulators. These results suggested that CBX family proteins, especially CBX3, might be potential biomarkers in the progression of EC.
| S-EPMC9498422 | biostudies-literature
Project description:Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality rates. The NT5DC family is an evolutionarily-conserved family of 5'-nucleosidases that catalyze the intracellular hydrolysis of nucleotides. Although the NT5DC family has been linked to the initiation and growth of several cancers, its function in PAAD remains unclear. A series of bioinformatic analyses was used to ascertain the expression, prognosis, gene changes, functional enrichment, and immune regulatory functions of the NT5DC family in PAAD. NT5C2 and NT5DC1/2 mRNA and protein levels are increased in PAAD. Furthermore, the high mRNA expressions of NT5C2, NT5DC2, and NT5DC4 indicate a poor prognosis in patients with PAAD. The enrichment of biological processes and gene expression in the NT5DC family in PAAD were investigated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Further investigations into immune infiltration revealed a close relationship between NT5DC gene expression and immune cell infiltration. These findings provide new insights into the biological function and prognostic value of the NT5DC gene family in PAAD.
| S-EPMC10414034 | biostudies-literature
Project description:Receptor interacting protein kinases (RIPKs) are a family of serine/threonine kinases which are supposed to regulate tumor generation and progression. Rare study illustrates the roles and functions of RIPKs family in lung adenocarcinoma (LUAD) comprehensively. Our results indicated that the expression of RIPK2 higher in LUAD patients while RIPK5 (encoded by gene DSTYK) expression was lower. Only RIPK2 had a strong correlation with pathological stage in LUAD patients. Kaplan-Meier plotter revealed that LUAD patients with low RIPK2 or RIPK3 level showed better overall survival (OS), but worse when LUAD patients with high RIPK5. Further, lower expression of RIPK2 and higher expression of RIPK1, RIPK4 and RIPK5 prompted a longer disease free survival (DFS). Genetic alterations based on cBioPortal revealing 16% alteration rates of RIPK2, as well as RIPK5. We also found that the functions of RIPKs family were linked to cellular senescence, protein serine/threonine kinase activity, apoptosis process et al. TIMER database indicated that the RIPKs family members had distinct relationships with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Moreover, RIPK2 could be observed as an independent prognostic factor with Cox proportional hazard model analysis. DiseaseMeth databases revealed that the global methylation levels of RIPK2 increased in LUAD patients. Thus, the findings above will enhance the understanding of RIPKs family in LUAD pathology and progression, providing novel insights into RIPKs-core therapy for LUAD patients.
| S-EPMC9365553 | biostudies-literature
Project description:BackgroundPancreatic adenocarcinoma (PAAD) is one of the most aggressive malignancies with a very poor prognosis. Exploring more therapeutic targets and prognostic biomarkers is of great significance to improve the prognosis of PAAD patients. Increasing evidence supports that the speckled protein (SP) 100 family is associated with human cancer and immune disorders. However, the function of the SP100 family members in PAAD is still unclear.MethodsR, Cytoscape, cBioPortal, and other software and online databases were used to comprehensively analyze the expression characteristics, prognostic value, and oncogenic mechanism of the SP100 family in PAAD.ResultsThe high expression of SP100 family members in PAAD was significantly correlated with poor clinicopathological features and poor prognosis of PAAD patients. Mechanistically, TP53 mutations were significantly associated with the expression levels of the SP100 family members, which were significantly coexpressed with M6A methylation regulators and were activated in multiple oncogenic pathways, including the EMT pathways. Moreover, we found that their expression levels were significantly correlated with the sensitivity of multiple traditional chemotherapeutic drugs.ConclusionThe SP100 family is closely related to the occurrence and development of PAAD and can be used as a new biomarker and therapeutic target for patients with PAAD.
| S-EPMC10333092 | biostudies-literature