The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

Xu, Peipei; Fan, Wei; Zhang, Zheng; Wang, June; Wang, Ping; Li, Yirong; Mu, Yu

doi:10.3389/fphys.2017.00950

Cited by 37 publications

(37 citation statements)

References 57 publications

(70 reference statements)

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“…Colorectal cancer (CRC) is one of the common malignant tumors of the digestive tract [1], which seriously threatens the life and quality of life of patients. In both sexes combined, the incidence of…”

Section: Introductionmentioning

confidence: 99%

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Qiang

Zhao

et al. 2020

J. Cancer

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Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Lymph node metastasis (LNM) is a common mode of metastasis of CRC. However, the combined mRNA biomarkers associated with LNM of CRC that can effectively predict CRC prognosis have not been reported yet. Methods: To identify biomarkers that are associated with LNM, we collected data from the The Cancer Genome Atlas (TCGA) database. The edgeR package was searched to seek LNM-related genes by comparisons between cancer samples and normal colorectal tissues and between LNM and non-LNM (NLNM) of CRC. Univariate and multivariate regression analysis of genes in the intersection to build gene signature associated with independent prognosis of CRC, and then verified by Kaplan-Meier curve and log-rank test, receiver operating characteristic (ROC) curve was used to determine the efficiency of survival prediction of our four-mRNA signature. Finally, the potential molecular mechanisms and properties of these gene signature were also explored with functional and pathway enrichment analysis. Results: 329 mRNAs were up-regulated in CRC tissues with LNM, and 8461 mRNAs were up-regulated in CRC tissues, the intersection is 100 mRNAs. After univariate and multivariate Cox regression analysis of 100 mRNAs, a novel four LNM related mRNAs (EPHA8, KRT85, GABRA3, and CLPSL1) were screened as independent prognostic indicators of CRC. Surprisingly, the four-mRNA signature can predict the prognosis of CRC patients independently of clinical factors andthe area under the curve (AUC) of the ROC is 0.730. The novel four-mRNA signature was used to identify high and low-risk groups. Stratified analysis indicated the risk score based on four-mRNA signature was an independent prognostic indicator for female, T3+T4, N1+N2 ,stage III+IV and patients with no new tumor event. Functional annotation of this risk model in high-risk patients revealed that pathways associated with neuroactive ligand-receptor interaction, estrogen signaling pathway, and steroid hormone biosynthesis. Conclusions: By conducting TCGA data mining, our study demonstrated that a four-mRNA signature associated with LNM can be used as a combined biomarker for independent prognosis of CRC.

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Section: Introductionmentioning

confidence: 99%

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Qiang

Zhao

et al. 2020

J. Cancer

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“…Tumour-infiltrating lymphocytes (TILs) are a dominant immune component found in the stroma of primary tumour CRC samples. High densities of CD3 + , CD8 + , and Foxp3 + T cells were associated with prolonged survival and a significant therapeutic response in CRC patients [11][12][13][14]. Furthermore, TIL localization might also be associated with their function and clinical effect.…”

Section: Introductionmentioning

confidence: 99%

Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy

Peng

Wang

Zhang

et al. 2019

Cancers

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Background: A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO) after liver metastasectomy. Methods: Simultaneous detection of the immune constituents CD3+, CD8+, Foxp3+ T, and α-SMA+ cells in the liver oligometastasis of 133 patients was conducted using a four-colour immunohistochemical multiplex technique. Immune cells were quantified, and tumour-infiltrating lymphocyte (TIL) ratios were subsequently calculated. Correlation analysis was performed using Pearson’s correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analysed using the Kaplan–Meier method and Cox regression models. Results: Significantly fewer CD3+, CD8+, and Foxp3+ T cells were observed in the intratumoural region than in the peritumoural region of liver metastases. CD3+, CD8+, Foxp3+ T, and α-SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. Only the CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p < 0.001). Patients with high intratumoural CD8/CD3 ratios had significantly longer 3-year RFS (59.0% vs. 47.4%, p = 0.035) and 3-year OS rates (83.3% vs. 65.8%, p = 0.007) than those with low intratumoural CD8/CD3 ratios. Multivariate analyses revealed that the intratumoural CD8/CD3 ratio was independently associated with RFS (HR = 0.593; 95% CI = 0.357–0.985; p = 0.043) and OS (HR = 0.391; 95% CI = 0.193–0.794; p = 0.009). Conclusion: These findings offer a better understanding of the prognostic value of immune cell infiltration on liver oligometastasis from colorectal cancer.

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“…For example, we have shown that activation of AhR by dietary indoles in a delayed-type hypersensitivity (DTH) model is essential for shifting the T cell response from a proinflammatory Th17 to an anti-inflammatory Treg phenotype [76]. This is important in regards to CRC as studies have shown that high expression of Tregs in CRC patients indicate a more favorable prognosis [77,78], whereas increased Th17 has been linked to CRC pathogenicity and tumor development [79][80][81]. The current report reinforces this notion, as gene expression data of CRC patients seemed to indicate that high expression of anti-inflammatory T cell factors (FoxP3, IL-10) improved patient survival, whereas proinflammatory makers linked to Th17 and Th1 phenotypes decreased overall survival in the patient population.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer

Alrafas

Busbee

Chitrala

et al. 2020

JCM

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Inflammatory bowel disease (IBD) is known to significantly increase the risk for development of colorectal cancer (CRC), suggesting inflammation and cancer development are closely intertwined. Thus, agents that suppress inflammation may prevent the onset of cancer. In the current study, we used resveratrol, an anti-inflammatory stilbenoid, to study the role of microbiota in preventing inflammation-driven CRC. Resveratrol treatment in the azoxymethane (AOM) and dextran sodium sulphate (DSS) CRC murine model caused an increase in anti-inflammatory CD4 + FOXP3 + (Tregs) and CD4 + IL10 + cells, a decrease in proinflammatory Th1 and Th17 cells, and attenuated CRC development. Gut microbial profile studies demonstrated that resveratrol altered the gut microbiome and short chain fatty acid (SCFA), with modest increases in n-butyric acid and a potential butyrate precursor isobutyric acid. Fecal transfer from resveratrol-treated CRC mice and butyrate supplementation resulted in attenuation of disease and suppression of the inflammatory T cell response. Data also revealed both resveratrol and sodium butyrate (BUT) were capable of inhibiting histone deacetylases (HDACs), correlating with Treg induction. Analysis of The Cancer Genome Atlas (TCGA) datasets revealed increased expression of Treg-specific transcription factor FoxP3 or anti-inflammatory IL-10 resulted in an increase in 5-year survival of patients with CRC. These data suggest that alterations in the gut microbiome lead to an anti-inflammatory T cell response, leading to attenuation of inflammation-driven CRC.

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The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

Cited by 37 publications

References 57 publications

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy

Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer

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