Regulated Polarization of Tumor-Associated Macrophages by miR-145 via Colorectal Cancer–Derived Extracellular Vesicles

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.

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Hsa_circ_0004831 serves as a blood-based prognostic biomarker for colorectal cancer and its potentially circRNA-miRNA-mRNA regulatory network construction

10.21203/rs.3.rs-55340/v3 ◽

2020 ◽

Author(s):

Linlin Xing ◽

Mengyan Xia ◽

Xin Jiao ◽

Ling Fan

Keyword(s):

Colorectal Cancer ◽

Extracellular Vesicles ◽

Regulatory Network ◽

Prognostic Biomarker ◽

Qpcr Assay ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Expression Level ◽

Blood Samples ◽

Tumorigenesis And Progression

Abstract Background: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC. Methods: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831. Results: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.Conclusions: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.

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The Impact of Tumor-associated Macrophages on Chemoresistance via Angiogenesis in Colorectal Cancer

Anticancer Research ◽

10.21873/anticanres.15253 ◽

2021 ◽

Vol 41 (9) ◽

pp. 4447-4453

Author(s):

MASATSUNE SHIBUTANI ◽

SHIGETOMI NAKAO ◽

KIYOSHI MAEDA ◽

HISASHI NAGAHARA ◽

SHINICHIRO KASHIWAGI ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Associated Macrophages ◽

The Impact

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Extracellular Vesicles in Colorectal Cancer Progression, Metastasis, Diagnosis, and Therapy

Colon Cancer Diagnosis and Therapy ◽

10.1007/978-3-030-64668-4_17 ◽

2021 ◽

pp. 401-420

Author(s):

Mercy Merlin ◽

Pranav Kumar Prabhakar ◽

Dhananjay Shukla ◽

Atul Kumar Tiwari ◽

Saurabh Saxena

Keyword(s):

Colorectal Cancer ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Diagnosis And Therapy ◽

Colorectal Cancer Progression

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CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood

International Journal of Molecular Sciences ◽

10.3390/ijms21165925 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5925

Author(s):

Daniëlle Krijgsman ◽

Natasja L. De Vries ◽

Morten N. Andersen ◽

Anni Skovbo ◽

Rob A.E.M. Tollenaar ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Outcome ◽

Disease Free Survival ◽

Soluble Form ◽

Clinicopathological Parameters ◽

Multiparameter Flow Cytometry ◽

Enzyme Linked Immunosorbent Assay ◽

Colorectal Tumors ◽

Blood Monocytes ◽

Tumor Associated Macrophages

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (N = 78) and healthy donors (N = 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS, p = 0.035) as well as disease-free survival (DFS, p = 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (p = 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (p = 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.

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Analysis of cancer-related mutations in extracellular vesicles RNA by Droplet Digital™ PCR

BioTechniques ◽

10.2144/btn-2020-0028 ◽

2020 ◽

Vol 69 (2) ◽

pp. 99-107

Author(s):

Soo Ann Yap ◽

Agnieszka Münster-Wandowski ◽

Anika Nonnenmacher ◽

Ulrich Keilholz ◽

Sandra Liebs

Keyword(s):

Colorectal Cancer ◽

Tumor Progression ◽

Extracellular Vesicles ◽

Liquid Biopsy ◽

Mek Inhibitor ◽

Diagnostic Information ◽

Braf V600e ◽

Plasma Samples ◽

Differential Centrifugation ◽

Potential Biomarkers

Extracellular vesicles (EVs) are taking their place as potential biomarkers in the field of liquid biopsy. In this study, EVs were isolated from plasma samples of 31 patients with colorectal cancer and melanoma via differential centrifugation and Droplet Digital™ PCR (Bio-Rad, CA, USA) was used to profile BRAF V600E/K, KRAS G12A/C/D/V and KRAS G13D mutations from EV-derived cDNA. The concordance rates with corresponding tissue were 54% and 44% in the colorectal cancer and melanoma cohort, respectively. Two patients displayed mutations in EVs not previously detected in tissue as evidence for emerging molecular resistance to anti-EGFR and BRAF/MEK inhibitor therapy prior to radiological evidence of tumor progression. We concluded that EV-derived nucleic acids may provide clinically relevant diagnostic information and mirror evolution of the disease.

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