Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics

Cai, Daxia; Liang, Ji‐Zhao; Cai, Xingdong; Yang, Ying; Liu, Gexiu; Zhou, Fenling; Dan, He

doi:10.21037/tcr-20-2712

Cited by 5 publications

(4 citation statements)

References 55 publications

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“…Thus, their overexpression might increase the sensitivity to NVA-AA treatment similar to WH-4-023, TGX211, and pazapanib treatments to other cancer cells. Moreover, the change in the expression of TUBA1C, PRDX4, LDHC, C7, and KNG1 due to NVA-AA treatment corroborated with the sensitivity provided by CTRP drugs to cancer cells (85). Thus, differential expression of proteins by NVA-AA NPs imparting sensitivity to the two cancer cells could be correlated to their sensitivities with the GDSC and CTRP drugs in different cancer cells.…”

Section: Discussionsupporting

confidence: 57%

Secretome profiling of Artemisia absinthium extract-loaded polymeric nanoparticle-treated MCF-7 and MDA-MB-231 revealed perturbation in microtubule assembly and cell migration

Kauser,

Mughees,

Mangangcha

et al. 2023

Front. Oncol.

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IntroductionArtemisia absinthium (wormwood) exhibits anticancer properties by inhibiting proliferation and causing cell death in breast cancer. Targeted drug delivery of A. absinthium nanoformulation using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles (NVA-AA NPs) was ensured by utilizing features of the tumor microenvironment, although their mechanism of action involved in cytotoxicity remains unknown.MethodsThe present study employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7; MDA-MB-231) by NVA-AA NPs for the determination of affected pathways and easily accessible therapeutic targets. Different bioinformatics tools were used to identify signature differentially expressed proteins (DEPs) using survival analysis by GENT2 and correlation analysis between their mRNA expressions and sensitivity toward small-molecule drugs as well as immune cell infiltration by GSCA.ResultsAnalysis by GENT2 revealed 22 signature DEPs with the most significant change in their expression regulation, namely, gelsolin, alpha-fetoprotein, complement component C3, C7, histone H2B type 1-K, histone H2A.Z, H2AX, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1-like, cytochrome c somatic, GTP-binding nuclear protein Ran, tubulin beta chain, tubulin alpha-1B chain, tubulin alpha-1C chain, phosphoglycerate mutase 1, kininogen 1, carboxypeptidase N catalytic chain, fibulin-1, peroxiredoxins 4, lactate dehydrogenase C, SPARC, and SPARC-like protein 1. Correlation analysis between their mRNA expressions versus immune cell infiltrates showed a positive correlation with antitumor immune response elicited by these NPs as well as a correlation with drug response shown by the GDSC and CTRP drugs in different cancer cells.DiscussionOur results suggest that NVA-AA NPs were able to invade the tumor microenvironment; transformed the communication network between the cancer cells; affected potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually caused cell death.

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Section: Discussionsupporting

confidence: 57%

Secretome profiling of Artemisia absinthium extract-loaded polymeric nanoparticle-treated MCF-7 and MDA-MB-231 revealed perturbation in microtubule assembly and cell migration

Kauser,

Mughees,

Mangangcha

et al. 2023

Front. Oncol.

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“…PPBP has been involved in various cellular processes and malignancies [48][49][50][51]; in fact, it has been found to be down-regulated in the plasma of patients with gastric cancer (GC), and has been suggested to be a diagnostic biomarker of that disease [49,52]. Our combination of gene expression profiling with a computational approach using STRING showed PPBP to be a hub gene in ALL, as has been observed in AML, and based on its important role in biological processes, PPBP could be considered a potential drug target in acute leukemias [53,54].…”

Section: Potential Biomarkers For Diagnosis and Prognosismentioning

confidence: 71%

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia

Cruz-Miranda,

Olarte-Carrillo,

Bárcenas-López

et al. 2024

IJMS

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Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein–protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

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“…We could observe that in cases where proteins were quantified with multiple peptides, all of them were significantly downregulated or upregulated. Here, cases such as the platelet basic protein (PPBP) in acute myeloid leukemia, which was previously identified as a dysregulated hub gene, can be highlighted [21]. Other examples are C1qB and C1qC, for which four peptides were identified as significantly downregulated in MM.…”

Section: Identification Of Potential Biomarkersmentioning

confidence: 98%

Absolute Quantification of Pan-Cancer Plasma Proteomes Reveals Unique Signature in Multiple Myeloma

Kotol,

Woessmann,

Hober

et al. 2023

Cancers

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Mass spectrometry based on data-independent acquisition (DIA) has developed into a powerful quantitative tool with a variety of implications, including precision medicine. Combined with stable isotope recombinant protein standards, this strategy provides confident protein identification and precise quantification on an absolute scale. Here, we describe a comprehensive targeted proteomics approach to profile a pan-cancer cohort consisting of 1800 blood plasma samples representing 15 different cancer types. We successfully performed an absolute quantification of 253 proteins in multiplex. The assay had low intra-assay variability with a coefficient of variation below 20% (CV = 17.2%) for a total of 1013 peptides quantified across almost two thousand injections. This study identified a potential biomarker panel of seven protein targets for the diagnosis of multiple myeloma patients using differential expression analysis and machine learning. The combination of markers, including the complement C1 complex, JCHAIN, and CD5L, resulted in a prediction model with an AUC of 0.96 for the identification of multiple myeloma patients across various cancer patients. All these proteins are known to interact with immunoglobulins.

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Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics

Cited by 5 publications

References 55 publications

Secretome profiling of Artemisia absinthium extract-loaded polymeric nanoparticle-treated MCF-7 and MDA-MB-231 revealed perturbation in microtubule assembly and cell migration

Secretome profiling of Artemisia absinthium extract-loaded polymeric nanoparticle-treated MCF-7 and MDA-MB-231 revealed perturbation in microtubule assembly and cell migration

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia

Absolute Quantification of Pan-Cancer Plasma Proteomes Reveals Unique Signature in Multiple Myeloma

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