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 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 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 Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Ji Ma ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Distribution Pattern ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

scholarly journals Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Distribution Pattern ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

scholarly journals Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Neck Tumors ◽  
Metastatic Lymph

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.

scholarly journals Lymph node metastasis in the space between the right carotid artery and jugular vein in papillary thyroid carcinoma

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052092003
Author(s):  
Jian Chen ◽  
Deguang Zhang ◽  
Liang Fang ◽  
Gaofei He ◽  
Li Gao
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Papillary Thyroid ◽  
Thoracic Inlet ◽  
Primary Tumor Size ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
The Right

Background The oblique brachiocephalic trunk and right common carotid artery constitute the right carotid sheath space (RCSS). The aim of this study was to detect the clinicopathologic factors associated with RCSS lymph node metastasis. Methods In total, 232 papillary thyroid carcinoma (PTC) patients with preoperative contrast-enhanced computed tomography scans were analyzed for associations between RCSS lymph node metastasis and clinicopathological factors. Results Among the 232 cases, 18 (7.76%) had suspicious RCSS lymph nodes, which was correlated with the presence of >5 metastatic lymph nodes, a larger thoracic inlet, and primary tumor size >2.15 cm. All pathologically confirmed metastatic lymph nodes were >1 cm in diameter. Conclusions The concept of “RCSS lymph node metastasis” was first introduced by this study. For PTC patients, a larger thoracic inlet, increased number of metastatic lymph nodes, and larger primary tumor size were related to RCSS lymph nodes, and more attention should be paid to patients who have lymph nodes >1 cm. A future prospective study will be designed to identify the potential risk factors for RCSS lymph node metastasis.

scholarly journals A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma

2021 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colorectal Carcinoma ◽  
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 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.

scholarly journals A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colorectal Carcinoma ◽  
Lymph Nodes ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Important Indicator ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

scholarly journals High Level of ASXL1 Protein Is Associated With Better Disease-Free Survival in Colorectal Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 200s-200s
Author(s):  
K. Lee
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Colorectal Cancers ◽  
Free Survival ◽  
Node Metastasis ◽  
Positive Expression ◽  
Disease Free

Background: ASXL1 gene is on chromosome region 20q11.21. Either amplification in cervical cancer or truncation mutations in colorectal cancers with microsatellite instability (MSI), malignant myeloid diseases, chronic lymphocytic leukemia, liver, prostate and breast cancers occurred. The functional and the prognostic roles of ASXL1 mutations and the expression of protein in colorectal cancer are still unknown. Aim: The aim of this study is to investigate the functional roles of ASXL1 mutations and the expression of protein in colorectal cancer. Methods: We performed NGS of 10 colorectal cancer with peritoneal seeding to find genetic markers for aggressive phenotype. All showed a frameshift deletion at codon 1934delG. To clinically validate the functional and the prognostic roles of the mutations, we performed an immunohistochemical staining (IHC) on tissue microarrays of 414 consecutive colorectal cancers. Results: The ASXL1 protein expression was strong positive in 5.8% (24 patients), moderate positive in 38.5% (157 patients) and negative in 55.6% (227 patients). The patients with negative ASXL1 expression had more lymph node metastasis than the patients with strong positive expression [59.0% (134/227 patients) vs 33.3% (8/24 patients), P = 0.038]. None of the patients with strong positive expression had recurrent disease in the stage I-III cancers [0% (0/21 patients) vs 19.4% (27/139 patients) vs 18.9% (34/180 patients)] and the disease-free survival rate of the patients with strong positive expression was significantly better than that of the patients with moderate positive or negative expression ( P = 0.037; P = 0.031). Conclusion: The decreased level of the expression of the ASXL1 protein was associated with lymph node metastasis in its progression of cancer. Strong positive ASXL1 protein expression was a 'good' prognostic factor of colorectal cancers. The ASXL1 protein might be tumor suppressive in colorectal cancer.

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