Showing 12 results for Colorectal Cancer
Fatemeh Mohammad Rezaei, Shahryar Hashemzadeh, Reyhaneh Ravanbakhsh Gavgani, Mohammadali Hosseinpour Feizi, Nasser Pouladi, Hossein Samadi Kafil, Leila Rostamizadeh, Vahid Kholghi Oskooei, Mohammad Taheri, Ebrahim Sakhinia,
Volume 8, Issue 3 (10-2019)
Abstract
Background: Colorectal cancer (CRC) is one of the most commonly-diagnosed malignancies throughout the world and the fourth-leading cause of cancer deaths globally. Angiogenesis and the resultant tumor neovascularization is a well-known cancer hallmark. Here we investigated the expression of FLT1 and KDR, the influential genes in angiogenesis regulation, in CRC patients.
Methods: We assessed FLT1 and KDR mRNA expression in 47 CRC samples and matched adjacent non-cancerous tissues (ANCT) by quantitative real-time PCR. The Spearmen correlation coefficient and receiver operating characteristic (ROC) curves were also examined.
Results: Both genes were expressed at significantly greater levels in CRC tissues than in ANCT (p < 0.05). A significant association was found between KDR expression and disease stage and lymph status in CRC patients. Furthermore, the Spearman correlation demonstrated a moderate correlation between FLT1 and KDR expression in CRC samples. Finally, ROC curve analysis demonstrated that FLT1 had the greatest sensitivity (85.1%), while the greatest specificity was achieved by a combination of the two genes.
Conclusions: The dysregulated FLT1 and KDR expression, in addition to the observed correlation and ROC curve results, indicate the critical importance of angiogenesis among the cancer pathways in CRC. These data can broaden our current knowledge of angiogenesis in CRC to improve disease diagnosis and patient treatment.
Zahra Taheri, Hamid Asadzadeh Aghdaei, Shiva Irani, Mohammad Hossein Modarressi, Zahra Noormohammadi,
Volume 8, Issue 3 (10-2019)
Abstract
Background: Abnormal DNA methylation leading to altered transcription of certain genes occurs frequently in colorectal cancer (CRC). As with protein-coding genes, microRNAs (miRNAs) may be targeted for methylation in CRC; however, the methylation state of miRNA genes in CRC, especially in primary lesions, has not yet been completely elucidated. To understand the impact of DNA methylation on the miR-200c/141 cluster promoter, we investigated the methylation and expression of miR-141 in precancerous lesions and colorectal cancer.
Methods: In this cross-sectional study, 208 colorectal tissue samples, including 34 tumor tissue samples, 60 precancerous lesions with matched normal adjacent tissues, and 20 normal tissue samples, were collected. Promoter methylation of the miR-200c/141 cluster was studied using methylation-specific PCR. MiR-141 expression was examined using quantitative real-time PCR.
Results: Our findings showed that the miR-200c/141 cluster promoter region was most frequently hypermethylated in colorectal tumors and adenomatous polyps, but unmethylated in hyperplastic polyp tissues (P < 0.001). DNA methylation of the miR-200c/141 cluster and the tumor stage were significantly correlated (P = 0.002); however, miR-141 expression difference between the tumor and polyp samples was not significant (p = 0.6).
Conclusions: The DNA methylation status of the miR-200c/141 cluster could serve as a progression marker from benign polyps to colorectal cancer.
Zahra Taheri, Hamid Asadzadeh Aghdaei, Shiva Irani, Mohammad Hossein Modarressi, Zahra Noormohammadi,
Volume 9, Issue 1 (5-2020)
Abstract
Background: Epigenetic changes in CpG islands of the promoter regions of homeostasis-related genes, including nuclear factor erythroid 2-related factor 2 (NRF2), have been shown to hold a significant role in the development of colorectal cancer. Therefore, we aimed to examine the DNA demethylation pattern of the NRF2 promoter region in cancerous lesions from patients with colorectal cancer and the association of methylation status with clinicopathological features in the Iranian population.
Methods: In this cross-sectional study, 114 colorectal tissue samples were collected. These samples included: 34 tumour tissue samples, 60 precancerous polyps, and 20 normal tissue samples. The promoter methylation status of the NRF2 gene was examined using methylation-specific PCR. Additionally, the relationship between the methylation status and the clinicopathological features was investigated.
Results: The frequency of NRF2 demethylation in the tumour samples was significantly higher compared to the polyp tissues (p= 0.003) and normal tissue (p= 0.009), indicating that cancerous colorectal tissues exhibit increased demethylation of the NRF2 promoter. After examining the demethylation status of tissue samples, the clinicopathological features were compared to the demethylation results. No significant association was found between NRF2 promoter demethylation and the clinicopathological features of patient samples.
Conclusions: Our findings suggest that the epigenetic modifications leading to NRF2 demethylation found in colorectal tumour samples may contribute to cancer progression from precancerous polyps to cancerous lesions.
Mohammad Reza Bayatiani, Azam Ahmadi, Reza Aghabozorgi, Fatemeh Seif,
Volume 9, Issue 4 (1-2021)
Abstract
Background: The WNT-pathway is involved in several cancers, including colorectal cancer (CRC). Many cell signaling components and pathways are controlled by microRNAs. The main purpose of the present study was to investigate the expression of hsa-miR-374, and its two target genes of the Wnt-pathway in CRC clinical samples.
Methods: In this study, we predicted the miRNAs targeting key genes of WNT-pathway using bioinformatics algorithms. The expression levels of hsa-miR-374, APC and GSK-3β on 48 pairs of Formalin-Fixed Paraffin-Embedded (FFPE) CRC tumors and marginal-tumors were evaluated using real time-PCR. Additionally, the hsa-miR-374a-5p precursor sequence was amplified by whole-blood DNA as a template. This amplicon was cloned into pEGFP-c1 expression vector and transfected into SW742 cells. Aside from this, MTT assay was performed to evaluate the effect of miR-374 on cell viability.
Results: The bioinformatics analysis indicated that hsa-miR-374 binds to the regulatory region the key components of WNT-pathway, including APC and GSK-3β considering the recognition elements and mirSVR scores. Our results revealed significant down-regulation of GSK-3β (0.94 times, p= 0.0098) and APC (0.96 times, p= 0.03) and up-regulation of miR-374 (1.22 times, p= 0.0071) on tumor samples compared with their normal pairs. Meanwhile, the results of the over-expression of miR-374 showed down-regulation of APC and GSK-3β. MTT-assay also indicated that the miR-374 increased cell survival.
Conclusions: The results of our study indicated a concomitant change in the expression of miR-374 and its two related target genes, in clinical samples of CRC. Hsa-miR-374 might be as a helpful biomarker or therapeutic target in CRC.
Ahmed Abd Temur, Farah Aqeel Rashid,
Volume 10, Issue 3 (11-2021)
Abstract
Background: Carcinoembryonic antigen (CEA) is a common gastrointestinal tumor biomarker. Irisin is adipo-myokines that has been suggested to have a potential role in cancer development. However, limited studies test irisin as biomarker in gastric and colorectal cancers. Therefore, this study aims to investigate whether CEA and irisin could be a potential diagnostic biomarker in gastric and colorectal cancer.
Methods: A case-control study consists of 90 subjects, 21 gastric cancer patients, 49 colorectal cancer patients and 20 control. Serum CEA was detected by fluorescence immunoassay (FIA) kit. Serum irisin was determined by enzyme-linked immunosorbent assay (ELISA) kit.
Results: Serum CEA increases significantly and serum irisin decreases significantly in gastric and colorectal cancer patients. According to Receiver Operating Characteristic (ROC) curve analysis, in gastric cancer, the area under curve of CEA is 1.00 (95% CI, 1.000-1.000, p< 0.0001). The diagnostic
cut-off of CEA is< 3.08 ng/ml with %100 sensitivity and 100% specificity. The area under curve of irisin is 0.94 (95% CI, 0.8177-1.000, p< 0.0001). The cut-off of irisin is> 30.2 ng/ml with %90 sensitivity and 100%, specificity. In colorectal cancer, the area under curve of CEA is 0.99 (95% CI, 0.9866-1.000, p<0.0001) and the diagnostic value< 2.6 ng/ml with %98 sensitivity and %100 specificity. The area under curve of irisin is 0.96 (95% CI, 0.9155-1.000, p< 0.0001). The diagnostic cut-off of irisin is> 41.9 ng/ml with 88.1sensitivity and 90.5 specificity.
Conclusions: CEA and irisin could be powerful potential diagnostic biomarkers which would be use for early detection of gastric and colorectal cancers.
Azam Ahmadi, Mohamd Reza Bayatiani, Fatemeh Seif, Jamshid Ansari, Parisa Rashidi, Mona Moghadasi, Mobarakeh Etemadi,
Volume 10, Issue 4 (1-2022)
Abstract
Background: Current cancer treatments include surgery, radiotherapy, chemotherapy, and immunotherapy. Despite these treatments, a main issue in cancer treatment is early detection. microRNAs (miRNAs) can be used as markers to diagnose and treat cancers. This study investigated the effect of radiotherapy on miR-374 expression, and APC and GSK-3β, two of its target genes, in the WNT pathway, in peripheral blood samples from radiotherapy-treated colorectal cancer (CRC) patients.
Methods: Peripheral blood was collected from 25 patients before and after radiotherapy. RNA was extracted from the blood and cDNA synthesized. miR-374, APC, and GSK-3β expression was determined by real-time polymerase chain reaction (RT-PCR) and the amplicons were sequenced. Finally, the data were statistically evaluated.
Results: Quantitative RT-PCR revealed significant down-regulation of miR-374 (0.63-fold) and upregulation of APC (1.12-fold) and GSK-3β (1.22-fold) in CRC patients after five weeks of radiotherapy. Sequencing of PCR-produced amplicons confirmed the conservation of mature and precursor sequences
encoding miR-374. miR-374 expression changed with time after radiotherapy treatment and related tumor grading. Increased age and tumor grade positively correlated with decreased miR-374 expression.
Conclusions: miR-374 expression, and that of its two target genes, APC and GSK-3β, changed after radiotherapy. These genes can likely be used as diagnostic radiotherapy markers in CRC.
Hooman Shalmashi, Sahar Safaei, Dariush Shanehbandi, Milad Asadi, Soghra Bornehdeli, Abdolreza Mehdi Navaz,
Volume 11, Issue 3 (11-2022)
Abstract
Background: Colorectal cancer (CRC) is still considered one of the prevalent cancers worldwide. Investigation of potential biomarkers for early detection of CRC is essential for the effective management of patients using therapeutic strategies. Considering that, this study was aimed to examine the changes in lncRNA FOXD2-AS1 expression through colorectal tumorigenesis.
Methods: Fifty CRC tumor tissues and fifty adjacent normal tissue samples were prepared and involved in the current study. Total RNA was extracted from the samples and then reverse transcribed to complementary DNA. Next, the expression levels of lncRNA FOXD2-AS1 were evaluated using real-time PCR in CRC samples compared to normal ones. Also, receiver operating characteristic curve analysis was used to evaluate the diagnostic value of FOXD2-AS1 for CRC.
Results: The obtained results showed that the expression level of FOXD2-AS1 gene was significantly (p<0.0001) up-regulated in tumor tissues compared to normal marginal tissues. Also, a significant correlation was observed between higher the expression of FOXD2-AS1and the differentiation of tumor cells. Furthermore, ROC curve analysis estimated an AUC value of 0.59 for FOXD2-AS1, suggesting its potential as a diagnostic target.
Conclusions: Taken together, the current study implied that tissue-specific upregulation of lncRNA FOXD2-AS1 might be appropriate diagnostic biomarkers for CRC. Nonetheless, more studies are needed to validate these results and further illustrate FOXD2-AS1 function through colorectal tumorigenesis.
Mona Elhelaly Elsherbeny, Alyaa Ramadan Elsergany, Olfat Gamil Shaker,
Volume 12, Issue 1 (4-2023)
Abstract
Background: Colorectal cancer (CRC) is considered the third most common cancer around the world and second in terms of mortality. A significant aspect in its development is genetics. The risk of CRC and other clinicopathologic characteristics were investigated in this work in relation to the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, in an Egyptian population.
Methods: 160 CRC patients and 160 healthy controls were enrolled in this case-control study. The lncRNA MEG3 rs7158663 was examined using TaqMan Real-time PCR. RT-PCR was used to assess the levels of serum MEG3 expression.
Results: A significant higher expression of ‘A’ allele (risk allele) and A/A genotype in CRC cases vs. control subjects (P <0.001) Participants with A/A genotype had 4.8 times higher odds to exhibit CRC. Serum MEG3 gene expression was generally low in CRC patients, and it was considerably lower in those with the rs7158663 AA genotype than those with the GG genotype (P <0.001). It was found that CRC patients with the rs7158663 GA genotype had lower serum MEG3 expression levels than those with the GG genotype (P <0.001).
Conclusions: MEG3 low expression and MEG3 rs7158663 (AA) were associated with CRC risk in Egyptian patients and may serve as a diagnostic and prognostic marker for CRC patients.
Saeid Mahmoudivar, Habib Zarredar, Milad Asadi, Venus Zafari, Shahriyar Hashemzadeh, Rojin Farzaneh, Touraj Asvadi Kermani,
Volume 12, Issue 4 (2-2024)
Abstract
Background: MicroRNAs (miRNAs) play pivotal roles in post-transcriptional regulation of gene expression and have emerged as crucial regulators in cancer development, progression, and metastasis. This study aimed to assess the expression profiles of miR-23, miR-223, miR-1246, and miR-150 in serum samples obtained from colorectal cancer (CRC) patients before and three months after surgery, in comparison to a healthy control group, to explore their biomarker potential.
Methods: A total of 50 blood samples were collected from patients with CRC (pre- and post-surgery), along with 50 samples from healthy controls. The relative expression levels of miR-23, miR-223, miR-1246, and miR-150 in the serum were quantified using quantitative real-time PCR.
Results: Our findings revealed upregulated expression levels of miR-23, miR-1246, and miR-223, while miR-150 exhibited significant downregulation in the serum of CRC subjects compared to healthy controls. Receiver operating characteristic (ROC) analysis indicated that miR-23 and miR-150 could distinguish CRC cases from controls with relatively high accuracy. Moreover, three months post-surgery, miR-23, miR-1246, and miR-223 serum levels were downregulated, and miR-150 was significantly upregulated. However, no significant correlations were observed between serum levels of the studied genes and the clinical features of our patients.
Conclusions: The serum levels of miR-23 and miR-150 hold promise as potential biomarkers for the diagnosis and prognosis of CRC.
Basheer Kadhum Kharmeet, Mohammad Khalaj-Kondori, Mohammad Ali Hosseinpour Feizi, Jafar Hajavi,
Volume 12, Issue 4 (2-2024)
Abstract
Background: Pro-inflammatory cytokines play critical roles in cancer pathobiology and have been considered potential targets for cancer management and therapy. Understanding the impact of cancer therapeutics such as 5-fluorouracil (5-FU) on their expression might shed light on development of novel combinational therapies. This study aimed to encapsulate 5-FU into PLGA and evaluate their effects on the expression of pro-inflammatory genes IL-9, IL-17-A, IL-23, and IFN-γ in the HT-29 cells.
Methods: PLGA-5-FU NPs were constructed and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The cytotoxicity was evaluated by MTT test and, the IC50 was identified. HT-29 cells were treated with different concentrations of the PLGA-5-FU NPs for 48 hours and, gene expression levels were analyzed by qRT-PCR.
Results: DLS and AFM analysis revealed that the prepared PLGA-5-FU NPs were negatively charged spherical-shaped particles with a mean size of 215.9 ± 43.3 nm. PLGA-5-FU NPs impacted the viability of HT-29 cells in a dose- and time-dependent manner. The qRT-PCR results revealed a dose-dependent decrease in the expression of IL-9, IL-17A, IL-23 and IFN-γ genes, and their expressions were significantly different in both 10 and 20 µg/mL treated groups compared to the control. However, although the treatment of HT-29 cells with 20 µg/mL free 5-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group.
Conclusions: PLGA-5-FU NPs significantly suppressed expression of the IL-9, IL-17A, IL-23 and IFN-γ genes, and the encapsulation of 5-FU into PLGA improved considerably impact of the 5-FU on the HT-29 cells.
Hossein Razzaghi, Mohammad Heiat, Ahmad Khoncheh, Mohammad Ali Abyazi, Majid Zaki-Dizaji,
Volume 13, Issue 3 (11-2024)
Abstract
Background: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. Early detection is crucial for improving survival rates. Liquid biopsies, specifically analyzing circulating tumor-educated platelets (TEPs), have emerged as a promising tool for early CRC detection and monitoring treatment efficacy. This study investigated the expression levels of two specific circRNAs, hsa_circ_0004771 and hsa_circ_0019120, in the platelets of patients with CRC, advanced polyps, and healthy controls.
Methods: Blood samples were obtained from 25 individuals with CRC, 25 individuals with advanced polyps, and 25 healthy controls. Platelet-derived total RNA was extracted, and expression analysis was conducted using reverse transcription quantitative PCR (RT-qPCR). Differential expression and receiver operating characteristic (ROC) curve analysis were performed using GraphPad Prism.
Results: Both circRNAs were found to be upregulated in platelets from individuals with advanced polyps and CRC compared to healthy individuals. However, the upregulation was statistically significant only for hsa_circ_0004771 in CRC patients (p-value = 0.0036) and for hsa_circ_0019120 in both advanced polyp (p-value = 0.0175) and CRC patients (p-value = 0.0356). The combined analysis of both circRNAs achieved an area under the curve (AUC) of 0.8348 (95% CI: 0.7131 to 0.9565) with a sensitivity of 84% and specificity of 80% (p-value = 0.0002).
Conclusions: This study showed that hsa_circ_0004771 and hsa_circ_0019120 dysregulated in both CRC and polyps and have potential as a novel diagnostic biomarker of CRC.
Marjan Ghiyasvand, Ardeshir Hesampour, Hossein Dabiri, Javad Arasteh,
Volume 13, Issue 3 (11-2024)
Abstract
Background: One of the deadliest cancers in the world, colorectal cancer has a dismal prognosis and a poor response to therapy. It was suggested that outer membrane vesicles (OMVs) produced by Escherichia coli (E. coli) are a powerful inducer of inflammation in intestinal epithelial cells. This research aimed to determine the anticancer potential of E. coli-derived OMVs using a colorectal cancer model.
Methods: Five distinct E. coli strains were collected for this study. Their OMVs were then isolated and characterized using dynamic light scattering (DLS) and scanning electron microscopy (SEM). The effects of E. coli-derived OMVs on colorectal cancer were evaluated in vitro and in vivo using a colorectal tumor model in nude mice.
Results: Obtained results showed that E. coli probiotic strains released spherical-shaped vesicles ranging from 5 to 200 nm. E. coli-derived OMVs showed that in the untreated group, a large portion of the tumor tissue continued to grow, with only a few cells undergoing apoptosis. Conversely, the OMV-treated group exhibited a higher number of apoptotic cells, highlighting the anticancer effects of E. coli-derived OMVs in colorectal cancer.
Conclusion: These results demonstrated that E. coli-derived OMVs can be employed as a potential treatment for colorectal cancer with minimal adverse effects. Mechanistic studies indicate that these vesicles may promote apoptosis and inhibit cell proliferation, supporting their therapeutic potential.
