scholarly journals Expression of Migration-Related Genes in Human Colorectal Cancer and Activity of a Disintegrin and Metalloproteinase 17

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Katarzyna Walkiewicz ◽  
Paweł Kozieł ◽  
Martyna Bednarczyk ◽  
Adam Błażelonis ◽  
Urszula Mazurek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Markers ◽  
Microarray Data Analysis ◽  
Human Colorectal Cancer ◽  
Normal Tissues ◽  
Significance Analysis ◽  
Expression Of Genes ◽  
Advanced Stages ◽  
A Disintegrin And Metalloproteinase ◽  
Colorectal Cancer Patients

Introduction.The ability to form metastases which depends on the mechanisms of cell migration is an important element of the progression of cancer. In the present study we analyzed the genes involved in the regulation of migration in colon cancer cells.Materials and Methods.A total of 20 pairs of surgically removed tumoral and healthy (marginal) tissues samples from colorectal cancer patients at clinical stages I-II and III-IV were analyzed. The isolation of RNA from CRC and normal tissues and its subsequent molecular analysis were performed according to manufacturer’s instructions. Microarray data analysis was performed using the GeneSpring 11.5 platform and Significance Analysis of Microarrays (SAM). In SAM analysis to identify significantly differentially expressed genes score andq-value parameters were used.Results.The largest increase in expression of genes was shown by MMP9, ADAM17, EphA2, and TIMP.Conclusions.Presented genes, especially ADAM17, MMP9, EphA2, TIMP1, ICAM 11, and CD4, may be used as prognostic markers of advanced stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor.

scholarly journals Overexpression of DDIT4 and TPTEP1 are associated with metastasis and advanced stages in colorectal cancer patients: a study utilizing bioinformatics prediction and experimental validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fahimeh Fattahi ◽  
Jafar Kiani ◽  
Mahdi Alemrajabi ◽  
Ahmadreza Soroush ◽  
Marzieh Naseri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epigenetic Alterations ◽  
Expression Levels ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Advanced Stages ◽  
Aggressive Tumor ◽  
Positive Correlations ◽  
Colorectal Cancer Patients ◽  
Rna Genes

Abstract Background Various diagnostic and prognostic tools exist in colorectal cancer (CRC) due to multiple genetic and epigenetic alterations causing the disease. Today, the expression of RNAs is being used as prognostic markers for cancer. Methods In the current study, various dysregulated RNAs in CRC were identified via bioinformatics prediction. Expression of several of these RNAs were measured by RT-qPCR in 48 tissues from CRC patients as well as in colorectal cancer stem cell-enriched spheroids derived from the HT-29 cell line. The relationships between the expression levels of these RNAs and clinicopathological features were analyzed. Results Our bioinformatics analysis determined 11 key mRNAs, 9 hub miRNAs, and 18 lncRNAs which among them 2 coding RNA genes including DDIT4 and SULF1 as well as 3 non-coding RNA genes including TPTEP1, miR-181d-5p, and miR-148b-3p were selected for the further investigations. Expression of DDIT4, TPTEP1, and miR-181d-5p showed significantly increased levels while SULF1 and miR-148b-3p showed decreased levels in CRC tissues compared to the adjacent normal tissues. Positive relationships between DDIT4, SULF1, and TPTEP1 expression and metastasis and advanced stages of CRC were observed. Additionally, our results showed significant correlations between expression of TPTEP1 with DDIT4 and SULF1. Conclusions Our findings demonstrated increased expression levels of DDIT4 and TPTEP1 in CRC were associated with more aggressive tumor behavior and more advanced stages of the disease. The positive correlations between TPTEP1 as non-coding RNA and both DDIT4 and SULF1 suggest a regulatory effect of TPTEP1 on these genes.

scholarly journals Soluble SIGLEC5: A New Prognosis Marker in Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3896
Author(s):  
Karla Montalbán-Hernández ◽  
Ramón Cantero-Cid ◽  
Roberto Lozano-Rodríguez ◽  
Alejandro Pascual-Iglesias ◽  
José Avendaño-Ortiz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Operating Characteristic ◽  
Prognostic Markers ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Significant Heterogeneity ◽  
Kaplan Meier ◽  
Prognosis Marker ◽  
Colorectal Cancer Patients ◽  
Healthy Participants

Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.

scholarly journals Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 71 ◽  
Author(s):  
Varun Sasidharan Nair ◽  
Salman M Toor ◽  
Rowaida Z Taha ◽  
Ayman A Ahmed ◽  
Mohamed A Kurer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
T Regulatory Cell ◽  
Peripheral Blood Mononuclear ◽  
Functional Studies ◽  
Normal Tissues ◽  
Pathway Analyses ◽  
Colorectal Cancer Patients

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.

scholarly journals Identification of differentially expressed circular RNAs in human colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Peili Zhang ◽  
Zhigui Zuo ◽  
Wenjing Shang ◽  
Aihua Wu ◽  
Ruichun Bi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Circular Rna ◽  
Expression Level ◽  
Circular Rnas ◽  
Human Colorectal Cancer ◽  
Expression Levels ◽  
Normal Tissues ◽  
Node Metastasis

Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

scholarly journals Exosomal proteases in colorectal cancer

2019 ◽  
Vol 5 (4) ◽  
pp. 117-126 ◽  
Author(s):  
E. A. Zambalova ◽  
M. R. Patysheva ◽  
A. A. Dimcha ◽  
S. N. Tamkovich ◽  
A. E. Grigor’eva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Blood Plasma ◽  
Metabolic Disorders ◽  
Tumor Grade ◽  
20S Proteasome ◽  
A Disintegrin And Metalloproteinase ◽  
Colorectal Cancer Patients ◽  
And Control ◽  
Edta Blood ◽  
In Blood Plasma

The objectiveis to evaluate the level of ADAM10 and ADAM17 (a disintegrin and metalloproteinase) proteases, as well as 20S-proteasomes in blood plasma exosomes of patients with colorectal cancer.Materials and methods. The study included 60 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. The material for the study was EDTA blood plasma. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of tetraspanin-associated (ADAM10 and ADAM17) and tetraspanin-non-associated (20S-proteasome) proteases was evaluated by flow cytometry and Western blotting.Results.A twice negative subpopulation (ADAM10–/ADAM17–) predominated in blood plasma exosomes of colorectal cancer patients and control patients. The level of ADAM10+/ADAM17– exosomes was significantly higher in the exosomes of the plasma of control patients. There were no significant differences between the ADAM10/ADAM17 subpopulations and the 20S-proteasome level, depending on sex, age and tumor grade. A decrease in the ADAM10+/ADAM17– subpopulation was found in patients with metastatic colorectal cancer with hematogenous metastases compared with patients with T2–4N1–2M0 and 20S-proteasome compared to T2–4N0M0. A decrease in ADAM10–/ ADAM17+ exosomes and 20S-proteasomes level was found in exosomes of patients with colorectal cancer with a metabolic syndrome  in comparison with patients without metabolic disorders.

scholarly journals Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chih-Hsiung Hsu ◽  
Cheng-Wen Hsiao ◽  
Chien-An Sun ◽  
Wen-Chih Wu ◽  
Tsan Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Methylation Status ◽  
Aberrant Methylation ◽  
Event Free Survival ◽  
Free Survival ◽  
Normal Tissues ◽  
Colorectal Cancer Patients

AbstractThis study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80–23.1; P for trend <0.01) and 8.01 (95% CI, 1.92–33.4; P for trend <0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.

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