scholarly journals Downregulation of miR-30c-5p Expression in Colorectal Cancer Tissue is Sex-Dependent

2021 ◽  
pp. S479-S487
Author(s):  
I HERICHOVA ◽  
R REIS ◽  
K HASAKOVA ◽  
M VICIAN
Keyword(s):  
Colorectal Cancer ◽  
Oestrogen Receptor ◽  
Tumor Tissue ◽  
High Expression ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Male And Female ◽  
Adjacent Tissue ◽  
Male Patients ◽  
Low Expression

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor β (ERβ) mRNA levels in tumor was tested. In males with low expression of ERβ, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERβ mRNA levels and in females. Accordingly, males with low expression of ERβ and high expression of miR-30c showed a better survival that those with low expression ERβ and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERβ mRNA in tumor tissue.

scholarly journals Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7101
Author(s):  
Justyna Gil ◽  
Paweł Karpiński ◽  
Maria M. Sąsiadek
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Field Cancerization ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Targeting Therapy ◽  
Autophagy Pathway ◽  
Using Data

The role of autophagy in colorectal cancer (CRC) pathogenesis appears to be crucial. Autophagy acts both as a tumor suppressor, by removing redundant cellular material, and a tumor-promoting factor, by providing access to components necessary for growth, metabolism, and proliferation. To date, little is known about the expression of genes that play a basal role in the autophagy in CRC. In this study, we aimed to compare the expression levels of 46 genes involved in the autophagy pathway between tumor-adjacent and tumor tissue, employing large RNA sequencing (RNA-seq) and microarray datasets. Additionally, we verified our results using data on 38 CRC cell lines. Gene set enrichment analysis revealed a significant deregulation of autophagy-related gene sets in CRC. The unsupervised clustering of tumors using the mRNA levels of autophagy-related genes revealed the existence of two major clusters: microsatellite instability (MSI)-enriched and -depleted. In cluster 1 (MSI-depleted), ATG9B and LAMP1 genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by DRAM1 upregulation. CRC cell lines were also clustered according to MSI-enriched/-depleted subgroups. The moderate deregulation of autophagy-related genes in cancer tissue, as compared to adjacent tissue, suggests a prominent field cancerization or early disruption of autophagy. Genes differentiating these clusters are promising candidates for CRC targeting therapy worthy of further investigation.

scholarly journals Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Chenyao Li ◽  
Guoqiang Yan ◽  
Libin Yin ◽  
Tao Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hazard Ratio ◽  
High Expression ◽  
Cochrane Library ◽  
Event Free Survival ◽  
Free Survival ◽  
High Event ◽  
Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

Homeobox B9: A potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10531-10531
Author(s):  
Yoshinori Hoshino ◽  
Tetsu Hayashida ◽  
Akira Hirata ◽  
Koji Okabayashi ◽  
Hiroki Ochiai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Surrogate Marker ◽  
Angiogenic Factors ◽  
High Expression ◽  
Mrna Levels ◽  
Tgfβ Signaling ◽  
Bevacizumab Treatment

10531 Background: Homeobox B9 (HOXB9) is known to be overexpressed in human breast cancer and profoundly related to tumorigenicity, lung metastasis and radio-resistance. (Hayashida, PNAS 2010, and Chiba, PNAS 2011). However, little is known about the relation between the expression of HOXB9 and angiogenesis in colorectal cancer (CRC). We aimed to clarify the impact of HOXB9 in CRC and evaluate the importance for bevacizumab treatment. Methods: The expression of HOXB9 in human CRC specimens was analyzed. Then, we introduced HOXB9 construct into human CRC cell lines and examined TGFβ signaling and angiogenic factors. Xenograft model was established by these cell lines either with or without the administration of bevacizumab (5mg/kg, weekly) intraperitoneally. Finally, we examined the mRNA levels of consecutive patients who were treated by chemotherapy with bevacizumab in our institute and calculated the Kaplan- Meier curve with log-rank test. Results: 47 of 69 surgical specimens (67%) showed positive expression of HOXB9 mRNA. The high HOXB9 mRNA levels significantly correlated with poor differentiation and liver metastasis. The HOXB9-overexpressed cell lines showed significantly higher expression of TGFβ signaling target genes and angiogenic factors. HOXB9 overexpression significantly increased tumor volume and burden with higher microvessel density in vivo, even though the cell proliferation decreased in vitro. Notably, HOXB9-overexpressed tumor was dramatically shrunk by administration of bevacizumab (tumor shrinkage rate; 93% vs. 42% in HT29, 83% vs. 27% in HCT116). Patients with high expression of HOXB9 in tumor showed significantly longer progression free and overall survival periods (n=39). Conclusions: Our results demonstrated that patients with high expression of HOXB9 in tumor had better prognosis with bevacizumab treatment but worse without. In vivo and in vitro experiments revealed that HOXB9 might orchestrate angiogenesis and establish positive feedback between cancer cells and microenvironment. Bevacizumab might inhibit the feedback to reduce tumor growth dramatically. Therefore, HOXB9 may work as a potential surrogate marker of bevacizumab treatment in CRC.

Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer

2010 ◽  
Vol 46 (4) ◽  
pp. 826-835 ◽  
Author(s):  
Cecilia Magnusson ◽  
Maryna Mezhybovska ◽  
Ester Lörinc ◽  
Eva Fernebro ◽  
Mef Nilbert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Good Prognosis ◽  
High Expression ◽  
Low Expression

scholarly journals Comprehensive analysis of ceRNA network of ERCC4 in colorectal cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12647
Author(s):  
Huixin Hu ◽  
Songyi Liu ◽  
Aining Chu ◽  
Jing Chen ◽  
Chengzhong Xing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Drug Sensitivity ◽  
Hazard Ratio ◽  
High Expression ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Cerna Network ◽  
Kaplan Meier

Objective ERCC4 is one of the most significant molecules of Nucleotide Excision Repair (NER), which has been researched due to its high expression in colorectal cancer (CRC). This study aimed to find out the ceRNA (competitive endogenous RNA) network of ERCC4 in CRC. Methods and Materials Pan cancer mRNA expression of ERCC4 was evaluated using TCGA database. The protein expression of ERCC4 was evaluated based on the Human Protein Atlas (HPA). We screened DElncRNAs and DEmiRNAs in two groups of ERCC4high and ERCC4low expression in CRC. Then a lncRNA-miRNA-ERCC4 regulatory network was constructed based on DElncRNAs and DEmiRNAs using Starbase database and visualized by Cytoscape software. Kaplan-Meier analysis was performed to evaluate the prognostic value of the ceRNA network. Further, RT-PCR was performed to validate the expression of the representative molecules in the ceRNA network in CRC and normal tissues. The relationship between drug sensitivity and these molecules were also evaluated using RNAactDrug database. Results ERCC4 was overexpressed in a variety of tumors at mRNA levels, including CRC. High expression of ERCC4 was also observed on protein level in CRC. A total of 1,885 DElncRNAs and 68 DEmiRNAs were identified from CRC samples in ERCC4high and ERCC4low expression groups. Predicted by the Starbase database, we got interacting miRNAs and lncRNAs of ERCC4 from the DEmiRNAs and DElncRNAs, and a lncRNA-miRNA-ERCC4 regulatory network was constructed. Kaplan-Meier survival curves results showed that miR-200c-3p (hazard ratio [HR] = 0.62, P = 0.032), MALAT1 (HR = 1.54, P = 0.016), and AC005520.2 (hazard ratio [HR] = 1.75, P = 0.002) were significantly associated with the prognosis of CRC. After validation by RT-PCR, we found that ERCC4 and MALAT1 were up-regulated in CRC compared with normal tissues, while miR-200c-3p was down-regulated. A strong negative correlation was observed between MALAT1 and miR-200c-3p. Drug sensitivity analysis showed that ERCC4, miR-200c and MALAT1 were all associated with Cisplatin. Conclusion We constructed a ceRNA network of ERCC4 in CRC, of which the MALAT1-miR-200c-3p-ERCC4 axis may be involved in the development, prognosis and chemotherapy sensitivity of CRC. These findings might provide novel clues and insights on the molecular mechanisms of ERCC4 and NER pathway in CRC.

scholarly journals Hyaluronan Metabolism is Associated with DNA Repair Genes in Breast and Colorectal Cancer. Screening of Potential Progression Markers Using qPCR

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 183
Author(s):  
Ina Sevic ◽  
Fiorella Mercedes Spinelli ◽  
Daiana Lujan Vitale ◽  
Antonella Icardi ◽  
Lucia Romano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Normal Tissue ◽  
Low Cost ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Dna Repair Genes ◽  
Adjacent Tissue ◽  
Progression Markers ◽  
Repair Genes

In this work, we compared mRNA levels of Hyaluronan (HA) metabolism members and BRCA genes, known to be involved in the tumoral process, between tumor and non-tumor adjacent tissue and its correlation with previously proposed biomarkers (ER, PR, HER2 and KI67) in order to assess their value as a progression biomarkers. We show alteration in HA metabolism in colorectal but not breast cancer. However, we found a decrease in Hyaluronidase 1 HYAL1 levels in the breast but not colorectal cancer. We also show lower HA levels in tumor compared with normal tissue that could indicate a possible influence of tumor on its surrounding “normal” tissue. In both breast and colorectal cancer, CD44 and BRCA2 showed a strong positive correlation. Besides, our results show first indicators that qPCR of the analyzed genes could be used as an easy and low cost procedure for the evaluation of molecular markers we propose here.

Abstract 4917: High expression of miR-181c in tumor tissue as a recurrence marker of Dukes B colorectal cancer

2016 ◽  
Author(s):  
Yoshikatsu Koga ◽  
Nobuyoshi Yamazaki ◽  
Hirokazu Taniguchi ◽  
Motohiro Kojima ◽  
Yukihide Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Tissue ◽  
High Expression

scholarly journals High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases

Oncology ◽  
2020 ◽  
pp. 1-17
Author(s):  
Reetta Peltonen ◽  
Jaana Hagström ◽  
Taina Tervahartiala ◽  
Timo Sorsa ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Tumor Tissue ◽  
Prognostic Significance ◽  
Colorectal Tumor ◽  
High Expression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Tumors ◽  
Cox Regression Analysis ◽  
Postoperative Serum

<b><i>Introduction:</i></b> The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. <b><i>Methods:</i></b> Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method. <b><i>Results:</i></b> High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (<i>p</i> = 0.010), and high preoperative MPO in serum with improved DFS and OS (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases. <b><i>Conclusion:</i></b> Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.

scholarly journals The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Liang-Che Chang ◽  
Chung-Wei Fan ◽  
Wen-Ko Tseng ◽  
Hui-Ping Chein ◽  
Tsan-Yu Hsieh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Nrf2 Pathway ◽  
Normal Tissues ◽  
Serum Carcinoembryonic Antigen ◽  
Polymerase Chain

Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4–111.1%)) than in those without (101.0% (92.7–136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68–0.97) along with serum carcinoembryonic antigen (1.0027, 1.006–1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.

scholarly journals Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 967
Author(s):  
María I. Aroca-Siendones ◽  
Sara Moreno-SanJuan ◽  
Jose D. Puentes-Pardo ◽  
Michela Verbeni ◽  
Javier Arnedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Independent Prognostic Factor ◽  
High Expression ◽  
Incidence And Mortality ◽  
Circadian Clock Proteins ◽  
Low Expression

Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.

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