Prognostic Value of Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Shen, Haixiang; Jin, Ling; Chen, Shiming; Ma, Xueyou; Ying, Yufan; Li, Jiangfeng; Wang, Weiyu; Wang, Xiao; Xie, Liping

doi:10.3389/fonc.2021.657318

Cited by 32 publications

(34 citation statements)

References 66 publications

(118 reference statements)

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“…We observed that M2 macrophages may enhance the proliferation, migration, invasion, and EMT of ccRCC through CXCL13 in our study. This is consistent with the finding M2 macrophage infiltration is a poor prognostic factor for RCC in the majority of studies [ 21 ].…”

Section: Discussionsupporting

confidence: 92%

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

et al. 2021

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Objective M2 macrophages are associated with a poor prognosis in a variety of malignancies. There are, however, few relevant investigations in clear cell renal cell carcinoma (ccRCC). Methods The expression of M2 macrophages in ccRCC tissues was first discovered using immunohistochemistry in this study. Then, M2 macrophages were created in vitro to see how they affected the proliferation, migration, invasion, and EMT of ccRCC cells. Using qPCR and prognostic analysis identifies important chemokine. Antibody neutralization tests confirmed the chemokine’s involvement and function. Pathway inhibitors confirmed the main pathway of M2 macrophages in ccRCC. Finally, qPCR and IHC were used to confirm the expression of chemokine receptors in ccRCC tissues. Results The presence of M2 macrophages was linked to a poor outcome in ccRCC. M2 macrophages enhanced the proliferation, migration, invasion, and EMT of ccRCC lines in vitro. CXCL13 was identified as the main chemokine by prognostic analysis and qPCR tests. CXCL13 neutralizing antibodies can inhibit the stimulation of M2 macrophages in ccRCC lines’ proliferation, migration, invasion, and EMT. M2 macrophages and CXCL13 may activate the Akt pathway in ccRCC lines, and Akt inhibitors decrease ccRCC lines proliferation, migration, invasion, and EMT. CXCR5 expression is a poor prognostic factor for renal cell carcinoma, according to qPCR and immunohistochemistry. In vivo experiments further proved that CXCL13 secreted by M2 macrophages can promote tumor proliferation. Conclusions M2 macrophages in the immunological milieu secrete CXCL13, which promotes ccRCC proliferation, migration, invasion, and EMT. Our findings contribute to a better understanding of the function of the tumor microenvironment in the incidence and progression of ccRCC, and they may point to novel therapeutic targets for ccRCC.

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Section: Discussionsupporting

confidence: 92%

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

et al. 2021

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“…Thus, TGF-β1 and Notch signaling may participate in DLK2-promoted ribosome biogenesis in ccRCC. Reportedly, M2 macrophage infiltration is a risk factor for poor prognosis in ccRCC patients, and M2 macrophage can serve as a potential biomarker for prognosis and novel targets for immunotherapy in ccRCC [26]. Moreover, both TGF-β1induced Snail signaling and the Jagged1-mediated Notch pathway can also promote the M2 polarization of the macrophage in the tumor microenvironment [61,62], and this means that DLK2-activated TGF-β1 and Notch signaling may participate in the M2 polarization of the macrophage in the ccRCC tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been reported that ECM- [12,13], metabolism- [14][15][16], ribosome- [17], and immune-related genes [18][19][20][21] can serve as novel prognostic biomarkers for RCC. Moreover, the immune cell infiltration including T cells and macrophage also impacts disease prognosis in ccRCC [22][23][24][25][26]. These studied indicate that the genetic change in the tumor microenvironment can impact the survival outcome and disease prognosis in ccRCC patients.…”

Section: Introductionmentioning

confidence: 99%

DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis

Lee

Huang

et al. 2022

Genes

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Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with a high mortality. It has been reported that delta-like 1 homologue (DLK1) participates in the tumor microenvironmental remodeling of ccRCC, but the relationship between delta-like 2 homologue (DLK2, a DLK1 homologue) and ccRCC is still unclear. Thus, this study aims to investigate the role of DLK2 in the biological function and disease prognosis of ccRCC using bioinformatics analysis. The TNMplot database showed that DLK2 was upregulated in ccRCC tissues. From the UALCAN analysis, the overexpression of DLK2 was associated with advanced stage and high grade in ccRCC. Moreover, the Kaplan-Meier plotter (KM Plotter) database showed that DLK2 upregulation was associated with poor survival outcome in ccRCC. By the LinkedOmics analysis, DLK2 signaling may participated in the modulation of ccRCC extracellular matrix (ECM), cell metabolism, ribosome biogenesis, TGF-β signaling and Notch pathway. Besides, Tumor Immune Estimation Resource (TIMER) analysis showed that the macrophage and CD8+ T cell infiltrations were associated with good prognosis in ccRCC patients. Finally, DLK2 overexpression was associated with the reduced macrophage recruitments and the M1–M2 polarization of macrophage in ccRCC tissues. Together, DLK2 may acts as a novel biomarker, even therapeutic target in ccRCC. However, this study lacks experimental validation, and further studies are required to support this viewpoint.

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“…Then we validated the expression of CD 163 (marker of TAMs) and TGF beta 1 (marker of CAFs) in PAAD tissues and adjacent normal tissues. TAMs, especially M2-like TAMs, as a major group of immune cells in TME, were reported playing critical roles in in tumorigenesis and progression process like tumor growth, metastasis, and treatment resistance ( 5 , 19 , 20 ). CAFs are the most essential components of the TME.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Pan-Cancer Analysis of ADAMTS12 and Its Potential Implications in Pancreatic Adenocarcinoma

et al. 2022

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BackgroundA Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif 12 (ADAMTS12), a member of the ADAMTS family of multidomain extracellular protease enzymes, is involved in the progression of many tumors. However, a pan-cancer analysis of this gene has not yet been performed. Its role in pancreatic adenocarcinoma (PAAD) also remains unclear.MethodsThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data (GTEx) databases were used to analyze ADAMTS12 expression in pan-cancer. We assessed the expression, clinical characteristics, prognostic significance, copy number alteration, methylation, and mutation of ADAMTS12 and its correlation with the tumor immune microenvironment. qRT-PCR and immunohistochemistry assays were also performed to validate the expression of ADAMTS12 in PAAD.ResultsThrough bioinformatics analysis and preliminary experimental verification, ADAMTS12 was found to be substantially overexpressed in PAAD. High expression level of ADAMTS12 was correlated with worse survival rates in patients with PAAD and high infiltration levels of tumor-associated macrophages, cancer-associated fibroblasts, immune checkpoint proteins, and immunosuppressive genes.ConclusionOur findings suggest ADAMTS12 as a potential prognostic biomarker in PAAD. Elevated ADAMTS12 expression may also indicate an immunosuppressive microenvironment.

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Prognostic Value of Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Cited by 32 publications

References 66 publications

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

DLK2 Acts as a Potential Prognostic Biomarker for Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis

An Integrated Pan-Cancer Analysis of ADAMTS12 and Its Potential Implications in Pancreatic Adenocarcinoma

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