scholarly journals Node-Negative Colorectal Cancer at High Risk of Distant Metastasis Identified by Combined Analysis of Lymph Node Status, Vascular Invasion, and Raf-1 Kinase Inhibitor Protein Expression

2008 ◽  
Vol 14 (1) ◽  
pp. 143-148 ◽  
Author(s):  
I. Zlobec ◽  
K. Baker ◽  
P. Minoo ◽  
J. R. Jass ◽  
L. Terracciano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Protein Expression ◽  
Distant Metastasis ◽  
Vascular Invasion ◽  
Kinase Inhibitor ◽  
Lymph Node Status ◽  
Inhibitor Protein ◽  
Node Negative

scholarly journals CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

2020 ◽  
Author(s):  
Junwei Tang ◽  
Yifei Feng ◽  
Yuanjian Huang ◽  
Ziwei Xu ◽  
Dongsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Hepatic Metastasis ◽  
Vascular Invasion ◽  
Synchronous Liver Metastasis ◽  
Node Negative ◽  
Common Cancer ◽  
Tumor Tissues ◽  
Colorectal Cancer Patients

Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. Methods The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes. Results We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. Conclusions The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

scholarly journals Loss of Raf-1 Kinase Inhibitor Protein Expression Is Associated With Tumor Progression and Metastasis in Colorectal Cancer

2007 ◽  
Vol 127 (5) ◽  
pp. 820-827 ◽  
Author(s):  
Parham Minoo ◽  
Inti Zlobec ◽  
Kristi Baker ◽  
Luigi Tornillo ◽  
Luigi Terracciano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Tumor Progression ◽  
Kinase Inhibitor ◽  
Inhibitor Protein

scholarly journals Identification of Patients with High-risk Lymph Node-negative Colorectal Cancer and Potential Benefit from Adjuvant Chemotherapy

2004 ◽  
Vol 34 (6) ◽  
pp. 323-328 ◽  
Author(s):  
L. F. Onate-Ocana ◽  
R. Montesdeoca ◽  
C. M. Lopez-Graniel ◽  
V. Aiello-Crocifoglio ◽  
R. Mondragon-Sanchez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Potential Benefit ◽  
Node Negative

scholarly journals CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Junwei Tang ◽  
Chuan Zhang ◽  
Yuanjian Huang ◽  
Lu Wang ◽  
Ziwei Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Hepatic Metastasis ◽  
Vascular Invasion ◽  
Synchronous Liver Metastasis ◽  
Node Negative ◽  
Common Cancer ◽  
Tumor Tissues ◽  
Colorectal Cancer Patients

AbstractColorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly correlated with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. In conclusion, the circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

scholarly journals A Novel Seven Gene Signature-Based Prognostic Model to Predict Distant Metastasis of Lymph Node-Negative Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenting Peng ◽  
Caijin Lin ◽  
Shanshan Jing ◽  
Guanhua Su ◽  
Xi Jin ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Distant Metastasis ◽  
Prognostic Model ◽  
Cox Regression ◽  
Gene Signature ◽  
Training Set ◽  
Node Negative ◽  
Auc Value ◽  
Validation Set

BackgroundThe prognosis of lymph node-negative triple-negative breast cancer (TNBC) is still worse than that of other subtypes despite adjuvant chemotherapy. Reliable prognostic biomarkers are required to identify lymph node-negative TNBC patients at a high risk of distant metastasis and optimize individual treatment.MethodsWe analyzed the RNA sequencing data of primary tumor tissue and the clinicopathological data of 202 lymph node-negative TNBC patients. The cohort was randomly divided into training and validation sets. Least absolute shrinkage and selection operator Cox regression and multivariate Cox regression were used to construct the prognostic model.ResultsA clinical prognostic model, seven-gene signature, and combined model were constructed using the training set and validated using the validation set. The seven-gene signature was established based on the genomic variables associated with distant metastasis after shrinkage correction. The difference in the risk of distant metastasis between the low- and high-risk groups was statistically significant using the seven-gene signature (training set: P < 0.001; validation set: P = 0.039). The combined model showed significance in the training set (P < 0.001) and trended toward significance in the validation set (P = 0.071). The seven-gene signature showed improved prognostic accuracy relative to the clinical signature in the training data (AUC value of 4-year ROC, 0.879 vs. 0.699, P = 0.046). Moreover, the composite clinical and gene signature also showed improved prognostic accuracy relative to the clinical signature (AUC value of 4-year ROC: 0.888 vs. 0.699, P = 0.029; AUC value of 5-year ROC: 0.882 vs. 0.693, P = 0.038). A nomogram model was constructed with the seven-gene signature, patient age, and tumor size.ConclusionsThe proposed signature may improve the risk stratification of lymph node-negative TNBC patients. High-risk lymph node-negative TNBC patients may benefit from treatment escalation.

scholarly journals Effect of Raf kinase inhibitor protein expression on malignant biological behavior and progression of colorectal cancer

2015 ◽  
Vol 34 (4) ◽  
pp. 2106-2114 ◽  
Author(s):  
YUN WANG ◽  
LING-YUN WANG ◽  
FEN FENG ◽  
YANG ZHAO ◽  
MA-YAN HUANG ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Kinase Inhibitor ◽  
Biological Behavior ◽  
Inhibitor Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein

scholarly journals Increased LEF1 Expression and Decreased Notch2 Expression Are Strong Predictors of Poor Outcomes in Colorectal Cancer Patients

2013 ◽  
Vol 35 ◽  
pp. 395-405 ◽  
Author(s):  
Wen-Juan Wang ◽  
Yu Yao ◽  
Li-Li Jiang ◽  
Ting-Hua Hu ◽  
Jie-Qun Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Protein Expression ◽  
Distant Metastasis ◽  
Lymph Node Metastases ◽  
Tnm Stage ◽  
Tumor Node Metastasis Stage ◽  
Mrna And Protein Expression ◽  
Node Metastases

Background/Objective. We aimed to examine the expression of lymphoid enhancer factor 1 (LEF1) and Notch2 in colorectal cancer (CRC) and their association with clinicopathologic variables and CRC patients’ prognosis.Methods. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to assess the expression of LEF1 and Notch2 in 184 patients with CRC.Results. We observed a strong negative correlation between LEF1 expression and Notch2 expression (P<0.001). Both LEF1 mRNA and protein expression increased while the Notch2 mRNA and protein expression decreased in tumor specimens compared with the matched paratumorous normal tissue (P<0.001). An increase in LEF1 protein expression was significantly associated with lymph node metastases, distant metastasis, advanced TNM (tumor-node-metastasis) stage, and shorter overall survival. A decrease in Notch2 protein expression was associated with poorly differentiated tumors, lymph node metastases, distant metastasis, advanced TNM stage, and shorter overall survival of patients. In the multivariate Cox regression analysis, the LEF1 protein expression (P<0.001), Notch2 protein expression (P<0.001), TNM stage (P<0.001), and the combination of increased LEF1 protein coexpression and decreased Notch2 protein coexpression (P<0.001) were found to be independent prognostic indicators in CRC.Conclusion. Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients.

scholarly journals Construction and Analysis of a Colorectal Cancer Prognostic Model Based on N6-Methyladenosine-Related lncRNAs

2021 ◽  
Vol 9 ◽  
Author(s):  
Hanqian Zeng ◽  
Yiying Xu ◽  
Shiwen Xu ◽  
Linli Jin ◽  
Yanyan Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Prognostic Model ◽  
Clinical Staging ◽  
Risk Scores ◽  
Lymph Node Status ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Cancer Tissues

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.

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