Genomic analysis of the prognostic effect of tumor-associated neutrophil-related genes across 15 solid cancer types: an immune perspective

Hao, Yuying; Hu, Pingping; Zhang, Jiandong

doi:10.21037/atm-20-6629

Cited by 10 publications

(8 citation statements)

References 22 publications

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“…Several proteins involved in carcinogenesis or leukemogenesis are increased for clinical responders (ANO6, CHI3L1, CTSG, ELANE and FGR), suggesting that the sensitivity to ATRA/VP additionally depends on more general functions involved in cancer development. This last hypothesis is further supported by previous observations describing associations between some of these network members and prognosis/survival in certain malignancies [ 80 , 81 , 82 , 83 ]. Finally, immune-mediated mechanisms may also be important for chemosensitivity because ATRA/VP reduces the levels of circulating T cells [ 5 ] and members of the neutrophil degranulation network are regarded as a possible leukemia-associated antigen (proteinase 3, PRTN3) and as a regulator of antileukemic immune reactivity (major histocompatibility complex, class I, B; HLA-B).…”

Section: Discussionsupporting

confidence: 83%

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Hernandez-Valladares

Wangen

Aasebø

et al. 2021

Cancers

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All-trans retinoic acid (ATRA) and valproic acid (VP) have been tried in the treatment of non-promyelocytic variants of acute myeloid leukemia (AML). Non-randomized studies suggest that the two drugs can stabilize AML and improve normal peripheral blood cell counts. In this context, we used a proteomic/phosphoproteomic strategy to investigate the in vivo effects of ATRA/VP on human AML cells. Before starting the combined treatment, AML responders showed increased levels of several proteins, especially those involved in neutrophil degranulation/differentiation, M phase regulation and the interconversion of nucleotide di- and triphosphates (i.e., DNA synthesis and binding). Several among the differentially regulated phosphorylation sites reflected differences in the regulation of RNA metabolism and apoptotic events at the same time point. These effects were mainly caused by increased cyclin dependent kinase 1 and 2 (CDK1/2), LIM domain kinase 1 and 2 (LIMK1/2), mitogen-activated protein kinase 7 (MAPK7) and protein kinase C delta (PRKCD) activity in responder cells. An extensive effect of in vivo treatment with ATRA/VP was the altered level and phosphorylation of proteins involved in the regulation of transcription/translation/RNA metabolism, especially in non-responders, but the regulation of cell metabolism, immune system and cytoskeletal functions were also affected. Our analysis of serial samples during the first week of treatment suggest that proteomic and phosphoproteomic profiling can be used for the early identification of responders to ATRA/VP-based treatment.

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Section: Discussionsupporting

confidence: 83%

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Hernandez-Valladares

Wangen

Aasebø

et al. 2021

Cancers

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“…MPO is a member of the heme peroxidase superfamily and is mainly expressed in neutrophils and monocytes. Studies have shown that MPO targeted therapy can show a good prognostic survival status in LUAD patients (35), which is consistent with the results of our survival analysis (P < 0.001). The results of molecular docking show that the compound Q of SAIN can speci cally bind to MPO protein (a nity = -8.8 kcal/mol).…”

Section: The Role Of Mpo and Nqo1 In Nsclc Patientssupporting

confidence: 92%

Based on network pharmacology, using methods such as molecular docking and gene difference analysis, small molecule compounds for the treatment of lung adenocarcinoma and lung squamous cell carcinoma were screened in saussurea involucrata, and new therapeutic targets were discovered

Zhang

et al. 2021

Preprint

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Purpose: Based on systemic pharmacology and network pharmacology, to evaluate the therapeutic effect of saussurea involucrata (SAIN) on lung adenocarcinoma and lung squamous cell carcinoma (LUAD&LUSC) through clinical sample genetic difference analysis and compound-target molecular docking, and discover new The target of prevention or treatment of LUAD&LUSC. Materials and methods: Using the TCM System Pharmacology Database (TCMSP) as the starting point for preliminary selection of ingredients and targets (OB≥30%, DL≥0.18, n=9), with the GDC database as the end point, using Cytoscape 3.8, TBtools 1.082, AutoDock 4.2.6, R 4.0.4, PyMol and other tools have conducted a preliminary screening of the ingredients and targets of SAIN. In order to further screen the effective ingredients and targets, we used clinical samples from LUAD and LUSC from TCGA and GEPIA to perform genetic difference analysis (n=6), and perform biological process (BP) analysis (FDR) on these targets. ≤0.05, n=6), KEGG pathway analysis (FDR≤0.05, n=6), protein interaction network (PPI) analysis (n=6) and compounds-targets-pathways network analysis (n=6), obtain biological processes, disease pathways and various compounds regulated by targets-the relationship between targets and pathways. Through the precise molecular docking of ingredients and targets, we further screened the targets of the effective ingredients of SAIN (affinity≤-7.0 kcal/mol, H-Bond dist≤3.0, n=6) and visualized the data, Then these targets were verified by using PSORTⅡ, CELLO and BUSCA databases for subcellular localization prediction (n=6). Finally, use the large amount of TCGA clinical data provided by Cbiportal for the prognostic survival analysis of LUAD and LUSC for the genes obtained through the screening. , And consult a large number of documents to verify the results.Results: After screening, comparing, analyzing and verifying a series of data, it is finally confirmed that there are three main active ingredients in SAIN. They are Quercetin, Luteolin and Kaempferol, which mainly act on 6 protein targets. The target mainly regulates 20 signal pathways including Pathways in cancer, Transcriptional misregulation in cancer, EGFR tyrosine kinase inhibitor resistance, Adherens junction, IL-17 signaling pathway, Melanoma, Non-small cell lung cancer and MicroRNAs in cancer. The preventive or therapeutic effects of LUSC. Conclusion: There are three active compounds of Q, L and K in SAIN, which play a role in the treatment and prevention of NSCLC by directly or indirectly regulating the expression of genes such as MMP1, MMP3 and EGFR.

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“…IL-6 polymorphism was associated with survival prognosis of non-small-cell lung cancer (nSCLC) [ 23 ]. A genomic analysis revealed that high ELANE expression in LUAD was associated with a good prognosis [ 24 ]. In esophageal squamous cell carcinoma, CASP4 served as a prognostic biomarker and is associated with poor prognosis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of Pyroptosis‐Related Prognostic Signature and Immunological Infiltration in Lung Squamous Cell Carcinoma

Luo¹,

Jiang²,

Ding³

et al. 2022

BioMed Research International

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Background. Lung cancer is one of leading causes of human health threatening with approximately 2.09 million initially diagnosed cases and 1.76 million deaths worldwide annually. Pyroptosis is a programmed cell death mediated by Gasdermin family proteins. Pyroptosis could suppress the tumor oncogenesis and progression; nevertheless, pyroptosis could promote tumor growth by forming a suitable microenvironment. Methods. LASSO Cox regression analysis was performed to construct prognostic pyroptosis-related gene (PRG) signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUSC. Results. The expression of 26 PRGs were increased or decreased in LUSC. We also summarized simple nucleotide variation and copy number variation landscape of PRGs in LUSC. Prognosis analysis suggested a poor overall survival rate in LUSC patients with high expression of IL6, IL1B, ELANE, and CASP6. A pyroptosis-related prognostic signature was developed based on four prognostic PRGs. High-risk score LUSC patients had a poor overall survival rate versus low-risk score patients with an AUC of 0.565, 0.641, and 0.619 in 1-year, 3-year, and 5-year ROC curves, respectively. Moreover, the risk score was correlated with immune infiltration in LUSC. Further analysis revealed that pyroptosis-related prognostic signature was correlated with immune cell infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Conclusion. A bioinformatics method was performed to develop a pyroptosis-related prognostic signature containing four genes (IL6, IL1B, ELANE, and CASP4) in LUSC. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Further in vivo and in vitro studies should be conducted to verify these results.

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Genomic analysis of the prognostic effect of tumor-associated neutrophil-related genes across 15 solid cancer types: an immune perspective

Cited by 10 publications

References 22 publications

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Based on network pharmacology, using methods such as molecular docking and gene difference analysis, small molecule compounds for the treatment of lung adenocarcinoma and lung squamous cell carcinoma were screened in saussurea involucrata, and new therapeutic targets were discovered

Integrative Analysis of Pyroptosis‐Related Prognostic Signature and Immunological Infiltration in Lung Squamous Cell Carcinoma

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