Colonic Stem Cells Expression of Lgr5 and CD133 Proteins as Predictive Markers in Colorectal Cancer among Egyptian Patients

AIM: Colorectal cancer is the fourth common tumour in Egypt after lymphoid, breast and urinary tumours. The study aims to assess the expression of Lgr5 and CD133 in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa by immunohistochemical staining.MATERIAL AND METHODS: This prospective study was done on 100 patients presenting with colonic symptoms, patients were divided into four groups; group I including 20 patients in the control group, group II including 20 ulcerative colitis (U.C) patients, group III including 20 patients with adenomatous polyps and group IV including 40 patients with colorectal cancer (CRC).RESULTS: Lgr5 and CD133 expression was significantly higher in carcinoma than in adenomas, IBD and normal mucosa (P < 0.001). Lrg5 and CD133 was positively correlated with histological grade (P = 0.001), depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.004) and TNM stage (P < 0.001).CONCLUSION: Role of Lgr5 and CD133 as stem cell marker was expressed and presented with different expression in the normal colonic mucosa, adenoma and CRC and showed increased expression in an advanced stage of CRC. This may suggest its possible involvement in colorectal tumorigenesis and invasion.

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Assessment of vitamin D and VDR gene expression in colorectal cancer patients

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0008.2252 ◽

2015 ◽

Vol 51 (3) ◽

pp. 193-198

Author(s):

Joanna Berska ◽

Jolanta Bugajska ◽

Diana Hodorowicz-Zaniewska ◽

Krystyna Sztefko

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Serum Concentration ◽

Cancer Patients ◽

Colonic Mucosa ◽

Tumor Tissue ◽

Disease Stage ◽

Control Group ◽

Normal Colonic Mucosa ◽

Colorectal Cancer Patients

Background: Vitamin D insufficiency may increase risk and/or progression of cancer. Vitamin D acts through a nuclear receptor (VDR) which binding to vitamin D response elements causes changes in many genes expression. The aim: to assess the serum concentration of 25-hydroxycholecalciferol (25(OH)D3) and tissue VDR expression in colorectal cancer patients in relation to disease stage, tumor localization and disease progression. Material & Methods: The study group consisted of 39 patients with colorectal cancer (mean age 65,5±6,8 yrs, 23/16 male/female) and a control group consisted of 25 patients (mean age 51,0±6,9 yrs; 8/17 male/female) without gastrointestinal disease and without neoplasm. Serum level of 25(OH)D3 was measured by HPLC/UV. RNA was isolated from homogenized normal colonic mucosa and tumor tissue then RT-PCR was performed. Results: The mean serum concentration of 25(OH)D3 was lower in the colorectal cancer patients as compared to the control group. The difference was significantly lower only for the patients with the early stages of the disease (p<0.02) and for the patients with tumor present in rectum (p<0.03). Higher VDR expression in tumor tissue than in normal colonic mucosa was observed. For the patients with the early stages of the disease (stage A, B1, B2) higher expression of VDR as compared to the patients with advanced stages (stage C1, C2, D) was noticed. Moreover, VDR expression was higher in tumor tissue obtained from disease-free patients as compared to the patients with disease progression noted one-year-follow-up (p<0.04). Conclusion: Antitumor effect of vitamin D depends on VDR expression in tumor tissue.

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Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.7229 ◽

2009 ◽

Vol 27 (2) ◽

pp. 186-192 ◽

Cited By ~ 603

Author(s):

Paul Salama ◽

Michael Phillips ◽

Fabienne Grieu ◽

Melinda Morris ◽

Nik Zeps ◽

...

Keyword(s):

Colorectal Cancer ◽

Colonic Mucosa ◽

Tumor Tissue ◽

Early Stage ◽

Prognostic Significance ◽

High Density ◽

Prognostic Indicators ◽

Normal Colonic Mucosa ◽

Solid Cancer ◽

Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

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Risk factors for the diagnosis of colorectal cancer

10.21203/rs.3.rs-422225/v1 ◽

2021 ◽

Author(s):

Anna Lewandowska ◽

Grzegorz Rudzki ◽

Tomasz Lewandowski ◽

Aleksandra Stryjkowska-Góra ◽

Sławomir Rudzki

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Healthy Lifestyle ◽

Meat Consumption ◽

Red Meat ◽

World Health ◽

Control Group ◽

Group I ◽

Modifiable Factors ◽

Obese Subjects

Abstract Background: Colorectal cancer (CRC), defined as cancer of the colon or rectum, is one of the most frequently diagnosed cancers, and, according to the World Health Organisation database GLOBOCAN, it accounts for about 1.4 million new diagnoses annually worldwide. There is an association between the occurrence of colorectal cancer and non-modifiable risk factors, including age and hereditary factors, as well as with modifiable factors linked to the environment and lifestyle choices.Methods: The study included 800 patients, 400 diagnosed with colorectal cancer and 400 within the control group. The research was based on a clinical, direct, individual, structured, in-depth and focused interview. Assessment of activity and BMI was used according to WHO recommendations, as well as the expert system.Results: The average age of the patients was 64.53 ± 8.86 years, of the control group I - 59.64 ± 9.33 and the control group II - 57.5 (7.83). The association between the incidence of ulcerative colitis and the risk of colorectal cancer was clearly positive (p<0.001). Among obese subjects, the colorectal cancer risk was 1.27 (95% CI, 1.06-1.53) in comparison with non-obese subjects. The relative risk for current smokers was 2.17 (95% CI 1.79-2.66). Higher fat consumption and higher red meat consumption were also associated with the higher risk of colorectal cancer (p=0.01).Conclusions: Obesity, low physical activity, active and passive smoking and high salt and red meat consumption have been linked to a higher risk of colorectal cancer. The results give further evidence of the importance of maintaining a healthy lifestyle.

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The different immune profiles of normal colonic mucosa in cancer-free Lynch syndrome carriers and Lynch syndrome colorectal cancer patients

Gastroenterology ◽

10.1053/j.gastro.2021.11.029 ◽

2021 ◽

Author(s):

Lena Bohaumilitzky ◽

Klaus Kluck ◽

Robert Hüneburg ◽

Richard Gallon ◽

Jacob Nattermann ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Cancer Patients ◽

Colonic Mucosa ◽

Normal Colonic Mucosa ◽

Colorectal Cancer Patients

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Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

Tumori Journal ◽

10.1177/030089169608200102 ◽

1996 ◽

Vol 82 (1) ◽

pp. 6-11 ◽

Cited By ~ 7

Author(s):

Giuseppe Pappalardo ◽

Antonio Guadalaxara ◽

Giuseppe Maiani ◽

Giovanni Illomei ◽

Mauro Trifero ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin E ◽

Vitamin C ◽

Colonic Mucosa ◽

Genetic Alterations ◽

Colorectal Carcinogenesis ◽

Normal Colonic Mucosa ◽

Antioxidant Agents ◽

Β Carotene

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

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Pathomorphology of colonic mucosa in patients with chronic post-parasitic colitis

Kazan medical journal ◽

10.17816/kmj2008 ◽

2014 ◽

Vol 95 (6) ◽

pp. 934-938

Author(s):

I T Scherbakov ◽

N I Leonteva ◽

N V Chebyshev ◽

N M Gracheva ◽

B N Khrennikov ◽

...

Keyword(s):

Colonic Mucosa ◽

Pathological Process ◽

Surface Epithelium ◽

Control Group ◽

Parasitic Diseases ◽

Normal Colonic Mucosa ◽

Colon Mucosa ◽

Complex Evaluation ◽

Pathologic Features ◽

Hematoxylin And Eosin

Aim. To identify pathologic features of the colonic mucosa in patients with chronic post-parasitic colitis. Methods. Under the observation were 80 patients aged 38-42 years (38 men and 42 women) 1.5-2 years after undergoing parasitic diseases (amebiasis, giardiasis, diphyllobothriasis). In 19 patients due to the presence of dyspeptic phenomena colon mucosa was evaluated by morphometric parameters using grid of Avtandilov. The control group consisted of 6 patients with adaptive norm, in which by complex evaluation (bacteriology, parasitology, endoscopic, histologic) the pathology has not been revealed. Biopsies of colon mucosa were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with 1% aqueous solution of Alcian blue, Mayer’s hematoxylin and eosin; for morphometric analysis of 24 objective indicators - azure II-eosin by Romanovsky, with eosin methylene blue and thionine by Nicolas. Results. It was found that the mucosa in chronic post-parasitic colitis in all cases different from the normal colonic mucosa by registered parameters: the amebiasis - in 50% of cases, giardiasis - in 54.1%, with difillobotriosis - in 70.8%. In post-difillobotriosis colitis the number of fibroblasts in the lamina propria was reduced. Post-lyambliotic colitis characterized by hypertrophy of the surface epithelium and a high mitotic activity of the epithelium of intestinal glands. Conclusion. After undergoing parasitic diseases, in the colon mucosa preserved histological changes corresponding to chronic ulcerative colitis; post-amebiasis chronic colitis characterized by catarrhal-haemorrhagic inflammation, chronic post-lyambliotic - catarrhal-follicular, post-difillobotriosis - catarrhal-haemorrhagic inflammation with high activity of the pathological process and moderate atrophy of the intestinal glands.

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An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis

Cancer Informatics ◽

10.1177/1176935117716405 ◽

2017 ◽

Vol 16 ◽

pp. 117693511771640 ◽

Cited By ~ 7

Author(s):

Martha L Slattery ◽

Jennifer S Herrick ◽

John R Stevens ◽

Roger K Wolff ◽

Lila E Mullany

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Messenger Rna ◽

Colonic Mucosa ◽

Target Gene ◽

Target Genes ◽

Multiple Comparisons ◽

Normal Colonic Mucosa ◽

Seed Region ◽

Discovery Phase

Background: Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes. Methods: We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miRNAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations. Results: From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37, respectively. Conclusions: Our data suggest that miRNA target gene databases are incomplete; pathways derived from these databases have similar deficiencies. Although we know a lot about several miRNAs, little is known about other miRNAs in terms of their targeted genes. We encourage others to use their data to continue to further identify and validate miRNA-targeted genes.

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