Positive expression and correlation of chemokine receptor CXCR4 with nodal metastasis and prognosis in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15128-e15128
Author(s):  
K. Iqbal
Keyword(s):  
Colorectal Cancer ◽  
Chemokine Receptors ◽  
Disease Free Survival ◽  
Cxcr4 Expression ◽  
Vessel Density ◽  
Therapeutic Interventions ◽  
Cancer Tissue ◽  
Positive Expression ◽  
Tissue Specimens ◽  
Micro Vessel Density

e15128 Background: Colorectal cancer is one of the leading causes of cancer related deaths,with recurrence and metastasis as the primary reasons for mortality. New evidence hasimplicated Chemokines as the likely cause. We studied the positive expression of CXCR4 chemokine receptors in colorectal carcinoma and investigated its correlations to clinicpathologic characteristics and prognosis. Methods: Tumor tissue specimens of patients with colorectalcarcinoma (n = 67) who underwent surgery from January 2003 to December 2004 at the Department of Surgery, Tongji Hospital were collected. CXCR4 expression levels and tumor micro vessel density were evaluated by immunohistochemistry. Specimens were immunostained using formalin-fixed, paraffin-embedded tissues. The correlation between the CXCR4 expression and clinicopathological factors was evaluated Results: In 67 cancer tissue specimens, CXCR4 was positively expressed in 38 cases; positive rate being 56.7%. Positive expression of CXCR4 is associated with an increase incidence of nodal involvement, higher clinic stage, higher tumor micro vessel density and a lower 3-year disease free survival rate as compared to those with negative CXCR4 expression (P<0.05). Conclusions: Positive CXCR4 expression and high tumor micro vessel density are associated with poor prognosis and could be a potential predictive factor for recurrence or metastasis of colorectal cancer patients. So CXCR4 may be a potential target for specific therapeutic interventions in the future. No significant financial relationships to disclose.

scholarly journals Expression of miR-21 in Colorectal Cancer and Its Relationship with Clinicopathological Characteristics of Colorectal Cancer

2020 ◽  
Vol 3 (3) ◽  
pp. 40
Author(s):  
Jia Lei
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Clinicopathological Characteristics ◽  
Control Group ◽  
Cancer Tissue ◽  
Study Group ◽  
Node Metastasis ◽  
The Difference ◽  
Tissue Specimens

Objective: To investigate the expression of miR-21 in colorectal cancer cells, and to analyze the relationship between the level of miR-21 and the clinicopathological characteristics of colorectal cancer patients. Methods: 210 patients with colorectal cancer treated in our hospital from January 2016 to June 2019 were selected. Cancer tissue specimens (study group) and adjacent normal tissue specimens (control group) were surgically collected, and the quantitative quantitative PCR was used to detect and compare the miR-21 expression of the two groups. Results: The expression of miR-21 in the study group was higher than that in the control group, and the difference was statistically significant (P <0.05). There were significant differences among patients with early and intermediate TNM, patients with low differentiation and patients with moderate to high differentiation, patients with lymph node metastasis and patients without lymph node metastasis, patients with high infiltration and patients with low infiltration, patients with high CEA levels, and patients with low CEA, and the difference was statistically significant (P <0.05). Conclusion: In colorectal cancer, miR-21 is highly expressed, which is closely related to stage and differentiation, and can be used to reflect the patient’s condition.

scholarly journals Characterisation of the Expression of Neurotensin and Its Receptors in Human Colorectal Cancer and Its Clinical Implications

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1145
Author(s):  
Shengyang Qiu ◽  
Stella Nikolaou ◽  
Jie Zhu ◽  
Peter Jeffery ◽  
Robert Goldin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Histological Grade ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Significant Risk Factor ◽  
Disease Recurrence ◽  
Cancer Tissue ◽  
Normal Epithelium ◽  
Free Survival

Introduction: Colorectal Cancer (CRC) accounts for 9% of cancer deaths globally. Hormonal pathways play important roles in some cancers. This study investigated the association of CRC expression of neurotensin (NTS), NTS receptors 1 and 3 (NTSR1 and NTSR3) and clinical outcomes. Methods: A prospective cohort study which quantifies the protein expression of NTS, NTSR1 and NTSR3 in human CRCs using immunohistochemistry. Expression levels were then compared with clinico-pathological outcome including histological grade, overall survival (OS) and disease-free survival (DFS). Results: Sixty-four patients were enrolled with median follow-up of 44.0 months. There was significantly higher expression of NTS in cancer tissue in CRC with higher T stages (p < 0.01), N stages (p = 0.03), and AJCC clinical stages (p = 0.04). There was significantly higher expression of NTS, NTSR1 and NTSR3 in cancer tissue compared to surrounding normal epithelium (median H-score 163.5 vs 97.3, p < 0.01). There was significantly shorter DFS in individuals with CRC with high levels of NTS compared to lower levels of NTS (35.8 months 95% CI 28.7–42.8 months vs 46.4 months 95% CI 42.2–50.5 months, respectively, p = 0.02). Above median NTS expression in cancer tissue was a significant risk factor for disease recurrence (HR 4.10, 95% CI 1.14–14.7, p = 0.03). Discussion: The expression of NTS and its receptors has the potential to be utilised as a predictive and prognostic marker in colorectal cancer for postoperative selection for adjuvant therapy and identify individuals for novel therapies targeting the neurotensinergic pathways. Conclusions: High NTS expression appears to be associated with more advanced CRC and worse DFS.

Hypermethylated promoters of genes UNC5D and KCNA1 as potential novel diagnostic biomarkers in colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1677-1688
Author(s):  
Sara Uhan ◽  
Nina Zidar ◽  
Aleš Tomažič ◽  
Nina Hauptman
Keyword(s):  
Colorectal Cancer ◽  
Candidate Genes ◽  
Promoter Hypermethylation ◽  
The Cancer Genome Atlas ◽  
Early Colorectal Cancer ◽  
Cancer Tissue ◽  
Promoter Regions ◽  
Diagnostic Biomarkers ◽  
Cancer Genome Atlas ◽  
Tissue Specimens

Aim: Identification of aberrant hypermethylation in promoter regions of candidate genes to discover potential biomarkers for colorectal cancer. Materials & Methods: Genes BMP2, IRF4, KCNA1, LRRC7, NRG3, SLC27A6 and UNC5D were pre-selected in a bioinformatics study for their hypermethylation status in colorectal cancer. Methylation analysis was performed on 202 cancer tissue specimens to validate candidate genes. Results: Genes KCNA1 and UNC5D displayed methylation in 95.3 and 99.7% of The Cancer Genome Atlas dataset samples and in 96 and 98% of our experimentally tested samples, respectively. Conclusion: KCNA1 and UNC5D promoter hypermethylation holds diagnostic biomarker potential in patients with early colorectal cancer.

scholarly journals DEAD-box RNA helicase protein DDX21 as a prognosis marker for early stage colorectal cancer with microsatellite instability

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Julia Y. Wang ◽  
Jinru Shia ◽  
Yihua Zhou ◽  
Makiko Ogawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Late Stage ◽  
Early Stage ◽  
Disease Free Survival ◽  
Rna Helicase ◽  
Cancer Tissue ◽  
Proteomic Profiling ◽  
Dead Box

AbstractDEAD-box RNA helicase DDX21 (also named nucleolar RNA helicase 2) is a nuclear autoantigen with undefined roles in cancer. To explore possible roles of autoimmune recognition in cancer immunity, we examined DDX21 protein expression in colorectal cancer tissue and its association with patient clinical outcomes. Unbiased deep proteomic profiling of two independent colorectal cancer cohorts using mass spectrometry showed that DDX21 protein was significantly upregulated in cancer relative to benign mucosa. We then examined DDX21 protein expression in a validation group of 710 patients, 619 of whom with early stage and 91 with late stage colorectal cancers. DDX21 was detected mostly in the tumor cell nuclei, with high expression in some mitotic cells. High levels of DDX21 protein were found in 28% of stage I, 21% of stage II, 30% of stage III, and 32% of stage IV colorectal cancer cases. DDX21 expression levels correlated with non-mucinous histology in early stage cancers but not with other clinicopathological features such as patient gender, age, tumor location, tumor grade, or mismatch repair status in any cancer stage. Kaplan–Meier analyses revealed that high DDX21 protein levels was associated with longer survival in patients with early stage colorectal cancer, especially longer disease-free survival in patients with microsatellite instability (MSI) cancers, but no such correlations were found for the microsatellite stable subtype or late stage colorectal cancer. Univariate and multivariate analyses also identified high DDX21 protein expression as an independent favorable prognostic marker for early stage MSI colorectal cancer.

scholarly journals A positive feedback loop of β-catenin/CCR2 axis promotes regorafenib resistance in colorectal cancer

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Baochi Ou ◽  
Xi Cheng ◽  
Zhuoqing Xu ◽  
Chun Chen ◽  
Xiaohui Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Chemokine Receptors ◽  
Feedback Loop ◽  
Disease Free Survival ◽  
Positive Feedback Loop ◽  
Ccr2 Expression ◽  
Underlying Mechanisms ◽  
Resistant Cells

Abstract Resistance to molecular targeted therapies is a significant challenge for advanced colorectal cancer (CRC). Understanding the underlying mechanisms and developing effective strategies against regorafenib resistance are highly desired in the clinic. Here, we screened the expression of chemokine receptors and identified CC chemokine receptor 2 (CCR2) as a top upregulated gene in regorafenib-resistant cells. CCR2 silencing alleviated drug tolerance in regorafenib-resistant cells, while overexpression of CCR2 enhanced CRC cells resistance to regorafenib. Moreover, CCR2-mediated regorafenib tolerance was demonstrated to be associated with AKT/GSK3β-regulated β-catenin stabilization. In turn, β-catenin modulation is sufficient to trigger the transcriptional activation of CCR2 expression. Clinically, high-CCR2 expression was correlated to shorter overall survival and disease-free survival of patients. A positive correlation between CCR2 and nuclear β-catenin expression was observed in a cohort of CRC tissues. Altogether, these findings suggest β-catenin and CCR2 are part of a positive-feedback loop, which sustains a high CCR2 expression level, conferring CRC cells resistance to regorafenib. Thus, targeting CCR2 may be a useful therapeutic strategy to alleviate regorafenib tolerance to increase the efficacy of CRC treatments.

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.

scholarly journals CLCA1 Has a Prognostic Indicator for the Colorectal Cancer by Weighted Gene Co-Expression Network Analysis

2021 ◽  
Author(s):  
jiajng lin ◽  
lingzhi yang ◽  
suyong lin ◽  
zhihua chen ◽  
shaoqin chen
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Network Analysis ◽  
Mrna Expression ◽  
Disease Free Survival ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Hub Gene

Abstract Colorectal cancer (CRC) has become the second most common digestive tract tumor. Even though the means to treat colon cancer have improved, patients prognosis is low due to the lack of accurate molecular targets. Hence, it urgently demanded better biomarkers for prognosis and progression of colon cancer. This study explores the hub gene associated with the prognosis of colorectal cancer and further analyzes the hub gene function. In this study, all genes mRNA expression data were from the cancer genome atlas (TCGA) colon cancer database and the Gene Expression Omnibus (GEO). These databases were used to screen the differentially expressed co-genes between colon cancer tissue and normal tissue. Weighted Gene Co-expression Network Analysis screened out a total of 103 differential co-expression genes (WGCNA). According to the R cluster profile package annotation analysis, these genes biological functions mainly concentrate on energy metabolism. Moreover, in the protein-protein interaction (PPI) network, the CytoHubba plugin of Cytoscape was used to screen out ten genes (CLCA1, ZG16, GUCA2B, GUCA2A, CLCA4, SLC26A3, MS4A12, GCG, SI, and NR1H4). According to the survival analysis results, high expression of CLCA1has better overall survival and disease-free survival in patients with CRC. Simultaneously, the mRNA expression of CLCA1 in normal tissues was higher than that in CRC tissues. Besides, there were significant differences in the expression of CLCA1 in pathological stage, T stage, and M stage. By using a gene set enrichment analysis, we found several considerable enrichment pathways in the high-groups. CIBERSORT analysis for the proportion of TICs revealed that B-cell naive, dendritic cells, plasma cells, and CD4+ T cells were positively correlated with CLCA1 expression, suggesting that CLCA1 might be responsible for the preservation of immune-dominant status for TME. Finally, in the Human Protein Atlas (HPA) database, the protein level of CLCA1 in the colorectal cancer samples decreased, consistent with the down-regulation of the mRNA expression level CLCA1. To sum up, by integrating WGCNA with differential gene expression analysis, this research generated a significant survival correlative gene called CLCA1 that can predict prognosis prediction in colon cancer.

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