Background: Acute myeloid leukemia (AML) is a common hematopoietic malignancy and have unsatisfactory prognosis. Our study aimed to identify hub genes in AML and explore potential biomarkers through integrated bioinformatics.Methods: Microarray datasets were analyzed to screen the differentially expressed genes (DEGs).Functional enrichment analysis was performed, and protein-protein interaction (PPI) network was generated by the STRING (11.0) database and Cytoscape (3.7.2) software. Hub genes were screened and verified through GEPIA2 and GEO microarray database. Sensitivity of AML cell lines with high expression of hub genes to the small-molecule drugs were identified using GSCA Lite.Results: A total of 456 DEGs were identified and top 100 genes were screened out, of which six genes (FLT3, PF4, CD163, MRC1, CSF2RB, PPBP) were upregulated in AML and individually had a worse prognosis by the overall survival (OS) analysis. AML cell lines with FLT3-overexpression and CSF2RB-overexpression were sensitive to most small-molecule drugs, while, AML cells with CD163-overexpression were only sensitive to a few drugs. However, sensitivity to Erlotinib was correlated with high expression of PF4 and PPBP.
Background Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. Methods The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0 and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry. Results The mRNA and protein expression of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expression of CBX2/3/5/6 was identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expression of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL was significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 overexpression was resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expression of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry. Conclusion We provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expression of CBX2/3/5/6 was associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and antitumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration.
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. The failure rate of treatment for its subsets is still very high. CXC chemokine, secreted by a variety of cells, is a vital component in the immune process. It also participated in the growth, development, and metastasis of tumors. This study aimed to explore the prognosis of CXC chemokines in DLBCL and the relationship with immune infiltration through bioinformatics analysis. Methods: We systematically analyzed the expression level and prognostic value of CXC chemokines in DLBCL patients, and the correlation between CXC chemokines and tumor immune infiltration through databases, such as Oncomine, GEO, GEPIA, GeneMANIA, DAVID, HPA, GenomicScape, and TIMER2.0. Results: With the comprehensive analysis of different databases, we found that CXC chemokines (CXCL1
Background: Acute myeloid leukemia (AML) is a common hematopoietic tumor with extremely high morbidity and mortality. This study was designed to explore candidate genes that were related to the poor prognosis of AML patients and analyze their relationship with drug sensitivity. Methods: Microarray databases were performed to screen the differentially expressed genes (DEGs). DAVID 6.8 was used for further functional enrichment analysis. The protein-protein interaction (PPI) network was constructed through STRING website and Cytoscape tool. Then, we analyzed and explored the mRNA transcription level, prognosis correlation, and drug sensitivity of the candidate genes in AML via multiple acknowledged databases including the GEPIA, BloodSpot, EMBL-EBI, UALCAN, LinkedOmics, and GSCALite databases. Results: A total of 181 up-regulated DEGs were screened. Three candidate genes (MAP2K3, LST1, and CYTH4) related to poor outcomes of AML patients were identified. Meanwhile, the high expression levels of the three genes were verified in AML patients and AML cell lines, the expression differences of three genes at AML different subtypes were demonstrated. Drug sensitivity analysis displayed the expression levels of MAP2K3, LST1, and CYTH4 were negatively related to drug resistance, indicating that the three genes were sensitive to certain small-molecule drugs (including targeted drugs and non-targeted drugs). Conclusion: In summary, MAP2K3, LST1, and CYTH4 may be potential prognostic indicators for AML, and may be associated with the sensitivity of certain small molecule drugs.
Background Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. Methods The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0, and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry. Results The mRNA and protein expressions of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expressions of CBX2/3/5/6 were identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expressions of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL were significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 over-expression were resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expressions of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry. Conclusion We provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expressions of CBX2/3/5/6 were associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and anti-tumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration.
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