WISP1 Predicts Clinical Prognosis and Is Associated With Tumor Purity, Immunocyte Infiltration, and Macrophage M2 Polarization in Pan-Cancer

Liao, Xia; Yang, Baofeng; Xu, Zihan; Jia, Fengan; Chang, Fan; Liang, Junrong; Jia, Qingan; Lv, Yi

doi:10.3389/fgene.2020.00502

Cited by 15 publications

(14 citation statements)

References 32 publications

(32 reference statements)

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“…Meanwhile, we also found that more than 10 genes associated with M1 phenotype were expressed significantly lower in P4 macrophages than P3 vice versa ( Figure 4 D). Gene regulation in macrophages for M1- and M2-associated phenotypes were previously described [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, we also found that more than 10 genes associated with M1 phenotype were expressed significantly lower in P4 macrophages than P3 vice versa (Figure 4D). Gene regulation in macrophages for M1-and M2-associated phenotypes were previously described [32][33][34][35][36][37][38][39]. However, there were no significant changes between P3 and P4 macrophages in the reaction with further IL-10 stimulus.…”

Section: A Selective Pressure For Cell Survival Was Initiated After Withholding Of M-csf Supplementmentioning

confidence: 87%

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Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

Chen

Lai

Hsuuw³

et al. 2021

IJMS

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Macrophage colony-stimulating factor (M-CSF or CSF-1) is known to have a broad range of actions on myeloid cells maturation, including the regulation of macrophage differentiation, proliferation and survival. Macrophages generated by M-CSF stimulus have been proposed to be alternatively activated or M2 phenotype. M-CSF is commonly overexpressed by tumors and is also known to enhance tumor growth and aggressiveness via stimulating pro-tumor activities of tumor-associated macrophages (TAMs). Currently, inhibition of CSF-1/CSF-1R interaction by therapeutic antibody to deplete TAMs and their pro-tumor functions is becoming a prevalent strategy in cancer therapy. However, its antitumor activity shows a limited single-agent effect. Therefore, macrophages in response to M-CSF interruption are pending for further investigation. To achieve this study, bone marrow derived macrophages were generated in vitro by M-CSF stimulation for 7 days and then continuously grown until day 21 in M-CSF absence. A selective pressure for cell survival was initiated after withdrawal of M-CSF. The surviving cells were more prone to M2-like phenotype, even after receiving interleukin-4 (IL-4) stimulation. The transcriptome analysis unveiled that endogenous CSF-1 level was dramatically up-regulated and numerous genes downstream to CSF-1 covering tumor necrosis factor (TNF), ras-related protein 1 (Rap1) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway were significantly modulated, especially for proliferation, migration and adhesion. Moreover, the phenomenal increase of miR-21-5p and genes related to pro-tumor activity were observed in parallel. In summary, withholding of CSF-1/CSF-1R interaction would rather augment than suspend the M-CSF-driven pro-tumor activities of M2 macrophages in a long run.

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Section: Resultsmentioning

confidence: 99%

“…Meanwhile, we also found that more than 10 genes associated with M1 phenotype were expressed significantly lower in P4 macrophages than P3 vice versa (Figure 4D). Gene regulation in macrophages for M1-and M2-associated phenotypes were previously described [32][33][34][35][36][37][38][39]. However, there were no significant changes between P3 and P4 macrophages in the reaction with further IL-10 stimulus.…”

Section: A Selective Pressure For Cell Survival Was Initiated After Withholding Of M-csf Supplementmentioning

confidence: 87%

Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

Chen

Lai

Hsuuw³

et al. 2021

IJMS

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show abstract

“…To clarify the functions of DEGs, we further performed functional enrichment analysis. The proteins translated by DEGs were mainly located in extracellular regions and these genes were primarily implicated in tumor-related biological processes such as cell adhesion, wound healing, and extracellular matrix organization (Yu et al, 2019;Alfarsi et al, 2020;Liao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma

et al. 2021

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BackgroundStomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study aimed to identify its potential biomarkers with the notion of revealing the underlying molecular mechanisms.MethodsGene expression profile microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The STAD dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another STAD dataset from the GEO database. CIBERSORT algorithm was used to characterize the 22 human immune cell compositions. The expression of LRFN4 and CTHRC1 in tissues was determined by quantitative real-time PCR from the patients recruited to the present study.ResultsThree public datasets including 90 STAD patients and 43 healthy controls were analyzed, from which 44 genes were differentially expressed in all three datasets. These genes were implicated in biological processes including cell adhesion, wound healing, and extracellular matrix organization. Five out of 44 genes showed significant survival differences. Among them, CTHRC1 and LRFN4 were selected for construction of prognostic signature by univariate Cox regression and stepwise multivariate Cox regression in the TCGA-STAD dataset. The fidelity of the signature was evaluated in another independent dataset and showed a good classification effect. The infiltration levels of multiple immune cells between high-risk and low-risk groups had significant differences, as well as two immune checkpoints. TIM-3 and PD-L2 were highly correlated with the risk score. Multiple signaling pathways differed between the two groups of patients. At the same time, the expression level of LRFN4 and CTHRC1 in tissues analyzed by quantitative real-time PCR were consistent with the in silico findings.ConclusionThe present study constructed the prognostic signature by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which provided the potential therapeutic targets of STAD for clinical treatment.

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“…To better clarify the functions of DEGs, we further performed functional enrichment analysis. The proteins translated by DEGs were mainly located in extracellular regions and these genes were primarily implicated in tumor-related biological processes such as cell adhesion, wound healing and extracellular matrix organization [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

A prognostic model constructed by CTHRC1 and LRFN4 in Stomach adenocarcinoma by Bioinformatics Analysis

Han

Zhu

Guan

et al. 2020

Preprint

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Background Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study specifically aimed to identify potential biomarkers and reveal the underlying molecular mechanisms. Methods Gene expression profiles microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The ‘limma’ R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The data of STAD cases with both RNA sequencing and clinical information of The Cancer Genome Atlas (TCGA) were obtained from Genomic Data Commons (GDC) data portal. Survival curves were analyzed by the Kaplan-Meier method, univariate Cox regression analysis and multivariate Cox regression were performed using ‘survival’ package. CIBERSORT algorithm used approach to characterize the 22 human immune cell composition. Gene expression profiles microarray data and clinical information were downloaded from GEO database to validate prognostic model. Results Three public datasets including 90 STAD patients and 43 healthy controls were used and 44 genes were differentially expressed in all three datasets. These genes were primarily implicated in biological processes including cell adhesion, wound healing and extracellular matrix organization. Seven out of 44 genes showed significant survival differences based on their expression differences. CTHRC1 and LRFN4 were eventually used to constructed risk score and prognostic model by univariate Cox regression and stepwise multivariate Cox regression in The Cancer Genome Atlas (TCGA)-STAD dataset. The group having high risk scores and the group having low risk scores had significant differences in the infiltration level of multiple immune cells including CD4 memory resting T cells, M2 macrophages, memory B cells, resting dendritic cells, eosinophils, and gamma delta T cells. Multivariate Cox regression analyses indicated that the risk score was an independent predictor after adjusting for age, sex, and tumor stage. At last, the model was verified and evaluated by another independent dataset and showed a good classification effect. Conclusions The present study constructed the prognostic model by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which may provide clinical guidance and potential therapeutic targets for STAD.

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WISP1 Predicts Clinical Prognosis and Is Associated With Tumor Purity, Immunocyte Infiltration, and Macrophage M2 Polarization in Pan-Cancer

Cited by 15 publications

References 32 publications

Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma

A prognostic model constructed by CTHRC1 and LRFN4 in Stomach adenocarcinoma by Bioinformatics Analysis

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