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

Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  

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.

2021 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal carcinoma 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 carcinoma.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma 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 carcinoma, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal carcinoma.


2021 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal carcinoma 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 carcinoma.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma 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 carcinoma, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal carcinoma.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background Lymph node metastasis is a major prognostic sign of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development by enhancing invasiveness and 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 carcinoma. Methods Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma 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 using immunohistochemistry. Furthermore, the relationships between M2 macrophages identified by expression of CD163 and lymph node metastasis were analyzed using the independent sample t-test and Chi-square test. Results M2 macrophages were increased in metastatic lymph nodes and non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in patients with micro-metastases. Conclusions The presence of M2 macrophages represents an important indicator for lymph node metastasis in colorectal carcinoma and may be a potential marker for its prediction. Thus, M2 macrophage localization might offer a new target for the comprehensive treatment of colorectal carcinoma.


2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  

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.


Author(s):  
Hang Du ◽  
Jingling Tang ◽  
Xiaoyun Li ◽  
Xinjun Wang ◽  
Liyun Wu ◽  
...  

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.


2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Ji Ma ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
...  

Abstract Background:Lymph node metastasis in the cervical region posterior to level V (PLV) often occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.Methods:We retrospectively studied 605 cases of NPC diagnosed by pathology from December 2011 to November 2017. All patients were subjected to an enhanced CT scan from the cranial apex to 2 cm below the sternoclavicular joints. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.Results:Lymph node metastasis occurred in 557 (92.06%) of 605 patients, and the top four areas with the highest probability of metastasis were level IIb (77.85%), level VIIa (73.05%), level IIa (60.0%), and level III (41.48%). There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean distance of the central point of each lymph node from the leading edge of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P=0.018), level Va, level Vb, and level Vc lymph node metastasis (all P<0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6%, 27.7%, 89.1%, and 47.3%, respectively. The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05).Conclusion:NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. When patients have lymph node metastasis in levels IVa and V, the posterior boundary of the radiotherapy target in ipsilateral level V should be appropriately moved backward. We recommend that the margin of the PLV region may be a new cervical lymph node segment for head and neck tumors.


2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  

Abstract Background:Lymph node metastasis in the cervical region posterior to level V (PLV) can occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.Methods:We retrospectively studied 605 cases of NPC diagnosed by pathological detection from December 2011 to November 2017. All patients were subjected to an enhanced CT scan from the cranial apex to 2 cm below the sternoclavicular joints. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.Results:Lymph node metastasis occurred in 557 (92.06%) of 605 patients, and the top four areas with the highest probability of metastasis were level IIb (77.85%), level VIIa (73.05%), level IIa (60.0%), and level III (41.48%). There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean vertical distance of the central point of each lymph node from the anterior surface of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P=0.018), level Va, level Vb, and level Vc lymph node metastasis (all P<0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6%, 27.7%, 89.1%, and 47.3%, respectively. The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05).Conclusion:NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. We recommend that the margin of the PLV region may be a new cervical lymph node segment for NPC.


2021 ◽  
Author(s):  
Yanlei Chen ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Xueqian Ma ◽  
Yanping Wang ◽  
...  

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.


2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  

Abstract Lymph node metastasis in the cervical region posterior to level V (PLV) often occurs in patients with nasopharyngeal carcinoma (NPC), but the significance and the delineation of the radiotherapy target area have not been reported. We retrospectively studied 605 cases of NPC. A total of 49 metastatic lymph nodes from the PLV region were counted. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa, level Va, level Vb, and level Vc lymph node metastasis (all P<0.05). The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05). In summary, NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. When patients have lymph node metastasis in levels IVa and V, the posterior boundary of the radiotherapy target in ipsilateral level V should be appropriately moved backward. We recommend that the margin of the PLV region may be a new cervical lymph node segment for head and neck tumors.


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