Dataset Information

Elevated CD163⁺/CD68⁺ Ratio at Tumor Invasive Front is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer.

ABSTRACT: Background: The interaction and crosstalk between tumor-associated macrophages (TAMs) and epithelial-mesenchymal transition (EMT) has been demonstrated to play a critical role in the progression and metastasis of multiple cancers. However, the roles of the M2-polarized TAMs in different tumor location in EMT and prognosis of colorectal cancer (CRC) have not been elucidated. Therefore, the present study was designed to set up a reliable ratio of CD163⁺/CD68⁺ to assess M2-polarized TAMs infiltration in the tumor center (TC) and tumor invasive front (TF) and to further evaluate their prognostic value and biological effects on tumor cells in CRC. Methods: TAMs markers (CD68 and CD163) and EMT markers (E-cadherin and Vimentin) expression were evaluated by immunohistochemistry in 81 patients with CRC. Circulating tumor cells (CTCs) of peripheral blood from above patients was also isolated. The correlation of CD163⁺/CD68⁺ ratio in different locations, EMT and CTCs counts were further analyses. Kaplan-Meier and the model analyses of univariate Cox proportional hazards were utilized to compare the survival of patients with high CD163⁺/CD68⁺ ratio with those with low CD163⁺/CD68⁺ ratio. Furthermore, the effects of the M2-polarized TAMs on growth, migration and invasion of CRC cells were explored in vivo and in vitro co-culture system. Results: The results showed that the level of CD163⁺/CD68⁺ ratio in TF was significant higher than that in TC, and higher CD163⁺/CD68⁺ _TF ratio were closely correlated with enhanced lymphovascular invasion, tumor invasion and TNM stage. Interestingly, higher CD163⁺/CD68⁺ _TF ratio were also significantly associated with EMT program and CTCs counts. Meanwhile, Kaplan-Meier analysis showed that CD163⁺/CD68⁺ _TF was associated with both recurrence-free survival (RFS) and overall survival (OS) of patients with CRC. Multivariate Cox regression analyses demonstrated that CD163⁺/CD68⁺ _TF remained an independent prognostic factor for RFS and OS. Further receiver operating characteristic (ROC) curve analysis found that CD163⁺/CD68⁺ _TF was a better prognosticator compared with CD68⁺ _TF and CD163⁺ _TF for CRC patients. What's more, M2-polarized TAMs secreted TGF-? to facilitate the EMT, growth, proliferation and invasion of CRC cells by in vivo and in vitro experiments. Conclusions: Our studies preliminarily elucidated the prognostic value of CD163⁺/CD68⁺ ratio in different tumor locations and the biological functions of M2-polarized TAMs in CRC progression via TGF-?.

SUBMITTER: Yang C

PROVIDER: S-EPMC6535793 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Elevated CD163+/CD68+ Ratio at Tumor Invasive Front is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer.

Yang Chaogang C Wei Chen C Wang Shuyi S Shi Dongdong D Zhang Chunxiao C Lin Xiaobin X Dou Rongzhang R Xiong Bin B

International journal of biological sciences 20190310 5

Background: The interaction and crosstalk between tumor-associated macrophages (TAMs) and epithelial-mesenchymal transition (EMT) has been demonstrated to play a critical role in the progression and metastasis of multiple cancers. However, the roles of the M2-polarized TAMs in different tumor location in EMT and prognosis of colorectal cancer (CRC) have not been elucidated. Therefore, the present study was designed to set up a reliable ratio of CD163+/CD68+ to assess ...[more]

PMID: 31182919

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Project description:Background: Glioma, the most common brain tumor, is a heterogeneous group of glia-derived tumors, the majority of which have characteristics of diffuse infiltration and immunosuppression. The LGALS protein family is a large class of sugar-binding proteins. Among them, LGALS3 has been reported to promote tumor development and progression in some cancers. However, the clinical significance and biological functions of LGALS3 in glioma remain virtually unknown. The purpose of our research is to detect LGALS3 expression and its prognostic value in glioma and reveal the relationship between its expression and the clinico/molecular-pathological features of patients and immune cell infiltration. Methods: LGALS3 protein expression was examined by immunohistochemistry. The mRNA expression data of LGALS3 was downloaded and analyzed from TCGA and Rembrandt datasets. The association between LGALS3 and glioma clinically relevant diagnostic/molecular markers (IDH, 1p19q, ATRX, MGMT, and TERT) was examined using the Chi-Squared (χ2) test. The correlation between LGALS3 expression and the infiltration of multiple intra-tumoral immune cell types, including B cells (CD20), T cells (CD4 and CD8), macrophages (CD68), and M2 tumor-associated macrophages (CD163), was evaluated by Spearman correlation analysis. Kaplan-Meier analysis and the Cox regression analysis were applied to evaluate the prognostic value of LGALS3 in glioma. The log-rank test was used to evaluate Kaplan-Meier results for significance. Results: Out of all 304 glioma cases, LGALS3 protein was expressed in 125 glioma cases (41.1%, 125/304), with 69.2% (9/13) in WHO I, 9.8% (8/82) in WHO II, 34.2% (26/76) in WHO III, and 61.7% (82/133) in WHO IV. The expression of LGALS3 was correlated with patient age, WHO grade, PHH3 (mitosis), Ki67 index, IDH, 1p/19q codeletion, and TERT promoter status. LGALS3 was an independent poor prognostic marker in diffusely infiltrating gliomas and was positively correlated with immune cell infiltration, particularly CD163+ tumor-associated macrophages in the TCGA dataset, Rembrandt dataset, and our SYSUCC cohort (R = 0.419, 0.627, and 0.724). Conclusion: LGALS3 was highly expressed in pilocytic astrocytoma, GBM, and IDH wild-type LGG. It served as a poor prognostic marker in diffusely infiltrating gliomas. Based on its prognostic significance and strong correlation with CD163+ TAMs, it may act as an important therapeutic target for human glioma.

Project description:ObjectivesThis study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.MethodsIFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.ResultsTwenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835).ConclusionsThe quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

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Dataset Information

Elevated CD163⁺/CD68⁺ Ratio at Tumor Invasive Front is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer.

Publications

Elevated CD163<sup>+</sup>/CD68<sup>+</sup> Ratio at Tumor Invasive Front is Closely Associated with Aggressive Phenotype and Poor Prognosis in Colorectal Cancer.

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