The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.
Long noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism How to cite this article: Sadeghi H, Nazemalhosseini-Mojarad E, Sahebi U, et al. Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer.
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.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, representing 13% of all cancers. The role of epigenetics in cancer diagnosis and prognosis is well established. MicroRNAs in particular influence numerous cancer associated processes including apoptosis, proliferation, differentiation, cell-cycle controls, migration/invasion and metabolism. MiRNAs-137 and 342 are exon- and intron-embedded, respectively, acting as tumour-suppressive microRNA via hypermethylation events. Levels of miRNAs 137 and 342 have been investigated here as potential prognostic markers for colorectal cancer patients. The methylation status of miRNA-137 and miRNA-342 was evaluated using methylation-specific (MSP) polymerase chain reaction (PCR) on freshly frozen tissue derived from 51 polyps, 8 tumours and 14 normal colon mucosa specimens. Methylation status of miRNA-137 and miRNA-342 was significantly higher in tumour lesions compared to normal adjacent mucosa. Surprisingly, the methylation frequency of miR-342 (76.3%) among colorectal cancer patients was significantly higher compared to miR-137 (18.6%). Furthermore, normal tissues, adjacent to the lesions (N-Cs), displayed no observable methylation for miRNA-137, whereas 27.2% of these N-Cs showed miRNA-342 hypermethylation. MiRNA-137 hypermethylation was significantly higher in male patients and miR-342 hypermethylation correlated with patient age. Methylation status of miRNA-137 and miRNA-342 has both diagnostic and prognostic value in CRC prediction and prevention.
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