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BACKGROUND AND AIM: Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic characteristics. CpG island methylator phenotype (CIMP) is found in about 15-20% of sporadic CRCs and is associated with hypermethylation of certain gene promoters. This study aims to find prognostic genes and compare their expression and methylation status as potential biomarkers in patients with serrated sessile adenomas/polyps (SSAP) and CRC, in order to evaluate which, one is a better predictor of disease. METHOD: This study employed a multi-phase approach to investigate genes associated with CRC and SSAP. Initially, two gene expression datasets were analyzed using R and Limma package to identify differentially expressed genes (DEGs). Venn diagram analysis further refined the selection, revealing four genes from the Weissenberg panel with significant changes. These genes, underwent thorough in silico evaluations. Once confirmed, they proceeded to wet lab experimentation, focusing on expression and methylation status. This comprehensive methodology ensured a robust examination of the genes involved in CRC and SSAP. RESULT: This study identified cancer-specific genes, with 8,351 and 1,769 genes specifically down-regulated in SSAP and CRC tissues, respectively. The down-regulated genes were associated with cell adhesion, negative regulation of cell proliferation, and drug response. Four highly downregulated genes in the Weissenberg panel, including CACNA1G, IGF2, MLH1, and SOCS1. In vitro analysis showed that they are hypermethylated in both SSAP and CRC samples while their expressions decreased only in CRC samples. CONCLUSION: This suggests that the decrease in gene expression could help determine whether a polyp will become cancerous. Using both methylation status and gene expression status of genes in the Weissenberg panel in prognostic tests may lead to better prognoses for patients.
Asunto(s)
Neoplasias Colorrectales , Islas de CpG , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Factor II del Crecimiento Similar a la Insulina , Homólogo 1 de la Proteína MutL , Proteína 1 Supresora de la Señalización de Citocinas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/genética , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Metilación de ADN/genética , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Islas de CpG/genética , Femenino , Pólipos del Colon/genética , Pólipos del Colon/metabolismo , Pólipos del Colon/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Masculino , Regulación hacia Abajo/genética , Simulación por Computador , Persona de Mediana Edad , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Regiones Promotoras Genéticas/genética , Canales de Calcio Tipo T/genética , Canales de Calcio Tipo T/metabolismo , Perfilación de la Expresión Génica/métodos , Anciano , PronósticoRESUMEN
CDKN1A gene is implicated in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. Somatic alterations and polymorphisms may interfere in the function of CDKN1A, and this could affect the individual susceptibility to colorectal cancer (CRC). Here in, we evaluated the importance of single nucleotide polymorphic variants in codon 31 of CDKN1A (rs1801270: C > A) for the development of colorectal cancer in an Iranian population. A total of 150 CRC patients and 150 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral blood specimens. Genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In CRC patients, the genotype frequencies detected were 90%, 8.0% and 2.0%2 for CC, AC and AA genotypes while the genotype frequencies in control group were 78%, 20.7% and 1.35% 1.35% for CC, AC and AA genotype, respectively. There were statistically significant differences in the distribution of CDKN1A rs1801270 genotypes and allele frequencies between colorectal cancer patients and healthy controls (p value = 0.021). Also, results indicated a significant negative association between AC genotype and risk of colorectal cancer occurrence. (Odds ratio (OR)=0.357; 95% confidence interval (CI)=0.168-0.760, p = 0.007). Our data suggest that the AC genotype may have a protective role in the development of CRC in an Iranian population.
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Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Humanos , Irán/epidemiología , Polimorfismo de Nucleótido Simple , Neoplasias Colorrectales/genética , Genotipo , Inhibidor p21 de las Quinasas Dependientes de la CiclinaRESUMEN
AIM: Here, we evaluated the VEGF gene -2578C/A polymorphism as a potential susceptibility factor in colorectal cancer (CRC) occurrence amongst Iranian CRC patients. BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulatory factor in angiogenesis which plays essential roles in the development of malignancy in colorectal cancer (CRC), as the third most prevalent cancer worldwide. METHODS: VEGF -2578C/A polymorphism was evaluated in 200 CRC patients and 200 healthy control subjects via restriction fragment length polymorphism analysis. RESULTS: The frequencies of CC, AC and AA genotypes among CRC patients were 22.5%, 51% and 26.5%, respectively, with their respective genotype frequencies at 16%, 54% and 30% in control cohorts (P=0.247). The A allele frequency among the case group was 52% and for control group, it was 57%. C allele frequency in case and control groups was 48% and 43%, respectively (p=0.156). No significant association was observed (p=0.990) between this polymorphism and CRC stage. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C/A VEGF are associated with increased risk of colorectal cancer in Iranian colorectal cancer patients and suggest instead that meta data studies, which have previously relied upon populations definitions such as 'Asian', should more specifically take into account country of origin when associating prognostic value to a given genotype.
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OBJECTIVE: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3.-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. METHODS: We genotyped NOD2 rs3135500 [3. untranslated region (UTR) A/G] and IL12B rs1368439 (3.UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. RESULTS: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). CONCLUSION: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.
Asunto(s)
Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Subunidad p40 de la Interleucina-12/genética , MicroARNs/genética , Proteína Adaptadora de Señalización NOD2/genética , Regiones no Traducidas 3'/genética , Adulto , Sitios de Unión/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Irán , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Colorectal cancer (CRC) is an important disorder that results from genetic and epigenetic alterations in one colonic epithelial cell. Epidermal growth factor (EGF) is critical in the development of tumors in epithelial tissues. Variations in the DNA sequence of the EGF gene may be particularly significant with regard to susceptibility to CRC. The present study aimed to investigate the effect of the EGF gene single nucleotide polymorphism (SNP), rs2298979, on CRC. In this prospective study, 220 samples were collected from patients with CRC and compared with 220 matched healthy controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the result was validated by direct sequencing. A significant correlation was observed between the rs2298979 variant in the EGF gene and CRC. The frequency of the A/G genotype in the control group was higher than in the patients with sporadic CRC [odds ratio (OR), 0.488; 95% confidence interval (CI), 0.307-0.774; P=0.002]. In this study there were no individuals with a G/G genotype. Although the frequency of the G and A alleles was similar in the healthy control and CRC patient groups, individuals with the A/G genotype were less susceptible to CRC compared with those with the A/A genotype.