Shaker Olfat Gamil, Mohammed Shereen Rashad, Mohammed Asmaa Mohammed, Mahmoud Zeinab
Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt.
J Clin Lab Anal. 2018 Jan;32(1). doi: 10.1002/jcla.22215. Epub 2017 Apr 4.
Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir-375 is frequently down-regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias.
Our aim was to study the expression of microRNA-375 and its target gene SMAD-7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC.
The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age- and sex-matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA-375 from serum was done by real-time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real-time PCR.
As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T-allelic frequency among cases and C-allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (-375) and the susceptibility to CRC as there is down-regulation of the microRNA-375 in CRC group with fold change in 0.42±0.27.
Micro RNA-375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.
结直肠癌（CRC）的发病率和死亡率都很高。许多研究报告称，mir-375在包括食管癌、肝细胞癌、乳腺癌和白血病在内的多种癌症中经常下调。
我们的目的是研究CRC患者与对照受试者相比，微小RNA-375及其靶基因SMAD-7多态性（rs4939827）的表达情况，并将这些结果与患者的临床数据相关联，以阐明它们在CRC发病机制和早期诊断中的作用。
本研究对122名受试者进行，分为86例CRC患者和36例年龄和性别匹配的对照。对所有受试者进行了以下操作：详细病史采集、全面临床检查、全血细胞计数、血清（谷丙转氨酶、谷草转氨酶）、血清白蛋白、癌胚抗原、白细胞计数、血小板计数和肌酐检测。通过实时聚合酶链反应检测血清中miRNA-375的基因表达。还通过实时聚合酶链反应对从血液中提取的DNA进行SMAD7（rs4939827）的基因多态性单核苷酸多态性检测。
关于SMAD7的多态性，我们发现与CRC病例相比，CC（野生型）基因型在对照中的比例较高（36.1%对15.1%）。同时，与对照相比，突变型和杂合子基因型在病例中的比例较高（分别为33.7%和51.2%）对（分别为22.2%和41.7%），无显著统计学分析差异。病例组中T等位基因频率有统计学意义的升高，对照组中C等位基因频率有统计学意义的升高。微小RNA（-375）的倍数变化与CRC易感性之间存在统计学显著关联，因为CRC组中微小RNA-375下调，倍数变化为0.42±0.27。
微小RNA-375和SMAD7中的rs4939827单核苷酸多态性可被视为检测和早期诊断CRC患者的潜在标志物。
