scholarly journals Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Hang Du ◽  
Jingling Tang ◽  
Xiaoyun Li ◽  
Xinjun Wang ◽  
Liyun Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Metastatic Lymph Node ◽  
Sentinel Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 as a top upregulated gene in SN. However, RNAscope assay showed that SIGLEC15 was not largely co-expressed with M2 macrophage marker CD163. We then selected eight pairs of lymph nodes for further cytological studies. Flow cytometry analysis revealed that Siglec-15 was expressed on all myeloid cell subsets. The relative expression of SEGLEC15 (SN/NSN) was correlated with the microsatellite instability (MSI) status in colorectal cancer patients. Further studies found that small interfering ribonucleic acid (siRNA)-mediated silencing of SLGLEC15 can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.

scholarly journals A Study of the Correlation Between M2 Macrophages and Lymph Node Metastasis of Colorectal Cancer

2020 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Comprehensive Treatment ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal cancer and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development, not only enhancing invasiveness, but also promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal cancer.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal cancer who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes by immunohistochemistry. Furthermore, the relationship between M2 macrophages identified by this marker and lymph node metastasis were analyzed using the independent sample T-test and Chi-square test.Results: M2 macrophages were increased not only in metastatic lymph nodes, but also in non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in those with micro-metastases.Conclusions: M2 macrophages represent an important factor for the promotion of lymph node metastasis in colorectal cancer, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal cancer.

scholarly journals Expression of M2 Macrophages and Regulatory T Cells in Colorectal Cancer and Their Correlation with Lymph Node Metastasis

2021 ◽  
Author(s):  
Yanlei Chen ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Xueqian Ma ◽  
Yanping Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Regulatory T Cells ◽  
Metastatic Lymph Node ◽  
M2 Macrophages ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
Cancer Tissues

Abstract BackgroundColorectal cancer (CRC) is among the most common malignancies worldwide. M2 macrophages and regulatory T cells (Tregs) are immunosuppressive cells that can promote tumor progression via inhibiting anti-tumor immunities. However, the significance and correlation of the two types of cells in colorectal cancer are still inconclusive. The purpose of this study is to detect the number of M2 macrophages and Tregs in colorectal cancer and lymph nodes and to explore the clinical and pathological significance of their existence.MethodsThe pathologic specimens and clinical data of 197 patients with Colorectal cancer after radical resection were collected. Immunohistochemical methods were used to detect the expression of M2 macrophages and Tregs in colorectal cancer tissues, adjacent tissues, and lymph node tissues in each group.ResultsCompared with adjacent tissues and non-metastatic lymph node tissues, M2 macrophages and Tregs not only increased significantly in cancer tissues and metastatic lymph node tissues (P < 0.001), but also M2 macrophages in non-metastatic lymph node tissues adjacent to cancer tissues the number of phages expressed also increased significantly (P < 0.05). In addition, there was a positive correlation between the number of cancer tissues and lymph nodes (P < 0.001).ConclusionM2 macrophages are involved in the formation of lymph node immunosuppressive environment and promote the development of CRC and lymph node metastasis together with Tregs. Upregulation of M2 macrophages and Tregs expression is a prognostic marker for monitoring the condition of colorectal cancer and judging the prognosis.

scholarly journals Gene Expression of Mesenchyme Forkhead 1 (FOXC2) Significantly Correlates With the Degree of Lymph Node Metastasis in Colorectal Cancer

2011 ◽  
Vol 96 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Toshiaki Watanabe ◽  
Takashi Kobunai ◽  
Yoko Yamamoto ◽  
Keiji Matsuda ◽  
Soichiro Ishihara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Node Metastases ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Node Metastasis ◽  
Node Metastases ◽  
Colorectal Cancer Patients

Abstract In stage III colorectal cancer, patients with N1 stage tumors show poorer outcome than patients with N2 stage tumors. Our objective was to identify genes that are predictive for the presence of lymph node metastasis, and to characterize the aggressiveness of lymph node metastases. Gene expression profiles of colorectal cancer were determined by microarray in training (n  =  116) and test (n  =  25) sets of patients. We identified 40 discriminating probes in patients with and without lymph node metastases. Using these probes, we could predict the presence of lymph node metastasis with an accuracy of 87.1% (training set) and 76.0% (test set). Among discriminating probes, FOXC2 expression was significantly correlated with the degree of lymph node metastasis. FOXC2 was expressed significantly and disparately in patients with N1 and N2 stage tumors as analyzed by real-time reverse transcriptase–polymerase chain reaction. FOXC2 appears to be involved in determining the aggressiveness of lymph node metastasis in colorectal cancer.

Loss of ASXL1 protein is associated with lymph node metastasis in colorectal cancer

2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background The function of ASXL1 protein in colorectal cancer has not been investigated yet. The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 protein expression on colorectal cancer.Methods We performed immunohistochemical staining of ASXL1 protein using tissue microarrays of 408 colorectal cancers, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. The intensity of expression was scored as 0–3, and the extent of staining was scored as 0–4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores.Results ASXL1 protein expression rates were 89.1% in normal mucosae, 72.9% in tubular adenomas, 44.4% in adenocarcinomas, and 28.3% in metastatic lymph nodes ( p < 0.001). With respect to the IRS cut-off score, the mean tumor size was smaller in the IRS 0–6 group than in the IRS 8–12 group (4.9 ± 2.1 vs. 6.3 ± 2.7 cm, p = 0.002). Lymph node metastasis was more frequent in the IRS 0–6 group than in the IRS 8–12 group (56.3% vs. 33.3%, p = 0.034). Lymphatic invasion was more frequent in the 0–6 group than in the IRS 8–12 group (56.0% vs. 33.3%, p = 0.035). The 5-year disease-free survival rate did not differ between two groups at stage II and stage III.Conclusions ASXL1 protein might act as a tumor suppressor in colorectal cancer. The loss of ASXL1 expression might be associated with metastasis via the lymphatic system to the lymph nodes.

scholarly journals The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients

Biomedicines ◽  
2018 ◽  
Vol 6 (1) ◽  
pp. 27 ◽  
Author(s):  
Noshad Peyravian ◽  
Pegah Larki ◽  
Ehsan Gharib ◽  
Ehsan Nazemalhosseini-Mojarad ◽  
Fakhrosadate Anaraki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Gene Expression Profiling ◽  
Cancer Patients ◽  
Expression Profiling ◽  
Node Metastasis ◽  
Colorectal Cancer Patients ◽  
Occult Lymph Node Metastasis

scholarly journals Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature

2021 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
Noshad Peyravian ◽  
Stefania Nobili ◽  
Zahra Pezeshkian ◽  
Meysam Olfatifar ◽  
Afshin Moradi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Candidate Genes ◽  
Case Series ◽  
Gene Expression Signature ◽  
Gene Panel ◽  
Expression Levels ◽  
Node Metastasis

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.

Sign in / Sign up

Export Citation Format

Share Document