scholarly journals Over-expression of Nav1.6 channels is associated with lymph node metastases in colorectal cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Shuiquan Lin ◽  
Yangbo Lv ◽  
Jianguang Xu ◽  
Xinglong Mao ◽  
Zhenhong Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Chemokine Receptors ◽  
Tumor Development ◽  
Node Metastasis ◽  
Key Factor ◽  
Nav Channels ◽  
The One

Abstract Background and objectives Lymph node metastasis is a key factor in predicting and determining the prognosis of patients with colorectal cancer (CRC). Sodium channels are highly expressed in a variety of tumors and are closely related to tumor development, metastasis, and invasion. We investigated the relationship between the expressions of different subtypes of Nav channels and lymph node metastasis of CRC. Methods Real-time PCR (RT-qPCR) was carried out to measure the expressions of different sodium channel subtypes, chemokine receptors (CCR2, CCR4, CCR7), and lymphocyte infiltration-related biomarkers (CD3e, CD8a, IL-2RA) in CRC tissues from 97 patients. The expressions of Nav1.5 and Nav1.6 in surgically isolated lymph nodes were detected by immunohistochemistry. Correlation analysis between expressions of different genes and lymph node metastasis was performed by two-tailed t test. Results Nav1.1 and Nav1.6 were highly expressed in CRC tissues and positively correlated with CRC lymph node metastasis. Nav1.6 was also highly expressed in metastatic lymph nodes. Further analysis showed that the high expression of Nav1.6 was closely related to the one of CCR2\CCR4 in tumor lymph node metastasis. Conclusions These results suggested that Nav1.6 might be a novel marker for CRC lymph node metastasis.

In vitro investigation of detectability of colorectal lymph nodes and diagnosis of lymph node metastasis in colorectal cancer using B-mode sonography

2003 ◽  
Vol 32 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Tsutomu Tateishi ◽  
Junji Machi ◽  
Ernest J. Feleppa ◽  
Andrew J. Oishi ◽  
Nancy L. Furumoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Node Metastasis ◽  
In Vitro Investigation

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 Loss of Atypical Chemokine Receptors Expression Promotes Lymph Node Metastasis of Colorectal Cancer

2021 ◽  
Author(s):  
Haitao Duan ◽  
Yao Huang ◽  
Caihua Zhang ◽  
Juanjuan Cui ◽  
Lianying Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Chemokine Receptors ◽  
Statistical Significance ◽  
Immunohistochemical Analysis ◽  
Pcr Analysis ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Cancer Tissues

Abstract Background: Atypical chemokine receptors (ACKRs), including DARC, D6 and CCX-CKR, hold very critical roles in cancer invasion and metastasis. The objective of the present study was to determine preliminarily the predictive value of ACKRs in colorectal cancer (CRC). Methods: From 2012 to 2019 in the First Affiliated Hospital of Dalian Medical University, 44 CRC patients were followed up. We performed immunohistochemical analysis, Western blot and RT-PCR analysis on CRC and adjacent normal tissues for investigating the expression of ACKRs and their relationships to clinicopathologic features and survival rate. Results: The expression of three ACKRs, CCX-CKR, DARC and D6, in normal colon tissues is higher than that in colorectal cancer tissues. Meanwhile, the expression of corresponding ligands CCL21, CCL2 and CCL22 shows the opposite. Low expression of ACKRs in colon cancer tissues was closely related to the potential of lymph node metastasis (P= 0.001). When compared with triple-negative ACKR expression, co-expression of the ACKRs predicted better outcomes of colorectal cancer patients with statistical significance (P=0.011). Conclusions: The loss of ACKRs may play important roles in lymph node metastasis of CRC. ACKR expression may be considered as prognostic markers in CRC patients.

Injection of Carbon Nanoparticles for Lymph Node Detection After Laparoscopic Colorectal Cancer Surgery

2021 ◽  
Vol 21 (2) ◽  
pp. 886-894
Author(s):  
Donghua Wang ◽  
Manyu Chen ◽  
Long Lv ◽  
Yu Chen ◽  
Kui Tian
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Treatment Plan ◽  
Regional Lymph Nodes ◽  
Colorectal Cancer Surgery ◽  
Lymphatic Gland ◽  
Node Metastasis

Colorectal cancer is the third most common cause of cancer-related death in the world because of its poor prognosis and many related complications. In clinical practice, lymph node metastasis is an important index to evaluate the recurrence and survival rate of patients with rectal cancer, it also the main method to determine the treatment plan of patients with rectal cancer. Nano carbon tracer can guide surgeons to clear regional lymph nodes accurately, improve the number of lymph nodes detected, and then improve the accuracy of pathological staging of rectal cancer. It has an important clinical significance in the removal of lymph nodes of middle and low rectal cancer, and provides an important basis for the development of postoperative adjuvant treatment plan. The purpose of this study is to explore the application value of this method in improving the detection rate of lymph nodes in laparoscopic colorectal cancer. According to the research results, the total number of lymphatic gland, the number of small lymphatic gland, the rate of lymph node metastasis, the number of black stained lymphatic gland and the number of lymphatic gland confirmed by pathology in the two groups were better than those in the traditional surgical treatment, which had better application value in the radical operation of 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.

The Lymph Node Metastasis Histology in Colorectal Cancer -The Clinical Implication of Tubular-Type Carcinoma in Lymph Nodes -

2021 ◽  
Author(s):  
Shozo Yokoyama ◽  
Takashi Watanabe ◽  
Yoichi Fujita ◽  
Shuichi Matsumura ◽  
Katsuya Ueda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Complete Response ◽  
Survival Times ◽  
Independent Predictive Factor ◽  
Node Metastasis ◽  
Tubular Type ◽  
Node Positive

Abstract Cribriform carcinoma in lymph nodes (LNs) is associated with distant metastasis, recurrence, and survival in node-positive colorectal cancer (CRC) patients. However, the clinical significance of lymph node metastasis histology remains to investigate. A total of 318 consecutive CRC patients who underwent a colectomy or anterior resection between January 2011 and June 2016 were enrolled, of whom 119 (37.4 %) had LN metastasis (LNM). Based on the LNM histology, patients with LNM were categorized into four groups: the group with tubular-type in all LNs (tub), with cribriform in at least one LN (cri), with mucinous-type in all LNs (muc), and with poorly differentiated-type carcinoma in at least one LN (por). We investigated the association among these histological types with the survival of these patients. The prognosis was good in order of muc, tub, cri, and por in node-positive CRC patients. Stage II and stage III tub groups did not have significantly different over-all survival times, but not recurrence-free survival times. Multivariate analyses revealed that all tubular-type carcinoma in LNs was independent predictive factor for longer survival times, clinical complete response and possible metastasectomy Diagnosis of lymph node metastatic histology is an important factor for patient stratification in node-positive CRC.

Upregulated CNTN1 is associated with lymph node metastasis and poor prognosis of colorectal cancer

2020 ◽  
pp. 1-9
Author(s):  
Guangyao Li ◽  
Zhengjun Zhang ◽  
Guochao Ge ◽  
Ke Fang ◽  
Jianyu Zhu
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Development ◽  
Normal Mucosa ◽  
Clinical Analysis ◽  
Immunoglobulin Superfamily ◽  
Node Metastasis ◽  
Adjacent Normal Mucosa ◽  
Potential Biomarker

BACKGROUND: Contactin1 (CNTN1), a member of the immunoglobulin superfamily, is known to correlate with tumor development and progression. Although recent studies have found that elevated CNTN1 has been demonstrated in some types of cancers, the expression and prognosis of CNTN1 in colorectal cancer (CRC) are unclear. Here, we aimed to determine the clinicopathological characteristics and prognostic role of CNTN1 in CRC patients. METHODS: The protein expression of CNTN1 in tumor tissues was evaluated by immunohistochemistry. In addition, the mRNA and protein expressions of CNTN1 were examined by qRT-PCR and Western blotting analysis in 40 matched adjacent normal mucosa samples. The relationships of CNTN1 with clinicopathological data and prognosis significance were analyzed. RESULTS: Immunohistochemical consequence suggested that the protein level of CNTN1 was obviously raised in CRC compared with adjacent normal mucosa tissues (56.9% vs 10.3%, P< 0.05). In addition, we detected a significant increase in CNTN1 mRNA and protein levels in CRC tissues compared with the matched adjacent normal mucosa tissues. Moreover, increased CNTN1 exprssion was significantly associated with tumor size, lymph node metastasis (LNM), tumor node-metastasis (TNM) stage and carcino-embryonic antigen (CEA) in clinical analysis. Kaplan-Meier analysis suggested that patients with CNTN1 over-expression showed worse overall survival (OS) (P= 0.001). Multivariate analysis indicated that high CNTN1 expression was an independent predictor for poor OS in CRC patients (P= 0.028). Further analysis revealed that patients with high CNTN1 combined with LNM present accurately predicted poorer outcome. CONCLUSION: Taken together, the findingsindicate that CNTN1 plays a significant role and serve as a potential biomarker for the prediction of adverse prognosis in CRC. Intriguingly, high express of CNTN1 + LNM-present combination may improve the accuracy of prognosis.

scholarly journals Impact of Inferior Mesenteric Artery Lymph Node Metastasis on the Prognosis of Patients With Left-sided Colorectal Cancer: A Case Control Study

2020 ◽  
Author(s):  
Kazuya Takabatake ◽  
Tomohiro Arita ◽  
masayoshi Nakanishi ◽  
Yoshiaki Kuriu ◽  
Yasutoshi Murayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Mesenteric Artery ◽  
Inferior Mesenteric Artery ◽  
Stage Iv ◽  
Stage Iii ◽  
Node Metastasis ◽  
Significant Difference

Abstract Background: The clinical significance of metastasis in inferior mesenteric artery (IMA) lymph node in patients with left-sided colorectal cancer (LCRC) is unclear. The aim of this study was to investigate the impact of IMA lymph node metastasis (IMA-LN (+)) on the prognosis of patients with LCRC. Methods: A total of 292 patients with stage III LCRC and 111 patients with stage IV LCRC who underwent radical resection of the primary tumor between 2005 and 2016 were included. The clinicopathological features and prognosis, which were retrospectively obtained from medical records, were compared regarding IMA-LN (+). Results: IMA-LN (+) was observed in 10 patients with stage III LCRC (2.3%). Moreover. ≥4 metastatic lymph nodes (p = 0.001) and poorly differentiated type (p = 0.049) were more frequently observed in patients with IMA-LN (+) than in patients without IMA lymph node metastasis (IMA-LN (-)) in stage III; IMA-LN (+) patients had significantly worse overall survival (OS) than IMA-LN (-) patients in stage III (p = 0.015). Conversely, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients (p = 0.192). Likewise, there was no significant difference between the OS of stage III IMA-LN (+) and stage IV patients with distant metastatic lymph nodes only (n = 12) (p = 0.294). Conclusion: The prognosis of IMA-LN (+) patients was worse than that of IMA-LN (-) patients in stage III LCRC; moreover, it was similar to that of patients with stage IV LCRC.

scholarly journals Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Paulina Lewandowska ◽  
Jaroslaw Wierzbicki ◽  
Marek Zawadzki ◽  
Anil Agrawal ◽  
Małgorzata Krzystek-Korpacka
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Chemokine Receptor ◽  
Growth Pattern ◽  
Chemokine Receptors ◽  
Receptor Expression ◽  
Transcriptional Analysis ◽  
Neoplastic Tissue ◽  
Node Metastasis ◽  
Affected Tissue

Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.

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