外周血胞裂蛋白9甲基化状态及其与结直肠癌的关系

Methylation status of Septin 9 in peripheral blood and its relationship with colorectal cancer

  • 摘要:
    目的 检测结直肠癌(CRC)患者外周血胞裂蛋白9(Septin 9)的甲基化状态, 分析Septin 9甲基化与CRC的关系。
    方法 选取120例CRC患者为研究对象,分析其外周血Septin 9甲基化状态与临床资料的关系; 分离CRC患者和健康人群的血清外泌体,采用该外泌体处理CRC细胞,测定CRC细胞的增殖和凋亡情况。
    结果 共计1586例体检人群接受了Septin 9筛查,其中Seprtin 9甲基化阳性56例,阳性率为3.5%。Sepetin 9阳性者中,胃肠状态异常者(肠胃炎症或者息肉)20例(35.7%), 而Septin 9阴性者胃肠状态异常率仅为5.4%(83/1530), 提示Septin 9在外周血中的甲基化状态与胃肠状态密切相关。120例CRC患者中, Septin 9甲基化阳性率为78.4%(73/93);在不同分化程度的比较中,高分化、中分化、低分化CRC患者的Septin 9甲基化阳性率依次为52.6%(10/19)、79.7%(59/74)、88.9%(24/27), 低分化CRC患者外周血Septin 9甲基化阳性率高于高分化组,差异有统计学意义(P=0.006)。外周血Septin 9甲基化的灵敏度为72.3%, 特异度为92.5%。Western blot结果显示CRC患者外泌体中Septin 9表达较健康人群降低,外泌体中Septin 9甲基化水平较正常人群上升,差异均有统计学意义(P=0.009、0.003)。本研究结果显示, CRC患者血清外泌体可促进细胞增殖,对细胞凋亡有抑制作用,差异有统计学意义(P < 0.05或P < 0.01)。
    结论 Septin 9可作为CRC早期筛查的标志物, CRC患者血清外泌体诱导的CRC增殖、凋亡抵抗可能是Septin 9的作用机制。

     

    Abstract:
    Objective To detect the methylation status of Septin 9 in the peripheral blood of patients with colorectal cancer (CRC) and analyze the relationship between the methylation of Septin 9 and CRC.
    Methods A total of 120 patients with CRC were selected as research objects, and the relationship between the methylation status of Septin 9 in the peripheral blood and the medical materials was analyzed; the serum exosomes isolated from patients with CRC and healthy people were used to treat the CRC cells, and the proliferation and apoptosis of CRC cells were detected.
    Results A total of 1 586 people with health examinations were screened for Septin 9, and 56 of whom were positive for methylation of Septin 9, with a positive rate of 3.5%. Among patients with Septin 9 positive, there were 20 cases (35.7%) with abnormal gastrointestinal status (gastrointestinal inflammation or polyps), while only 5.4% (83/1 530) of patients with Septin 9 negative had abnormal gastrointestinal status, which indicated that the methylation status of Septin 9 in the peripheral blood was closely related to the gastrointestinal status. Among 120 CRC patients, the positive rate of methylation of Septin 9 was 78.4% (73/93); in the comparison of different differentiation degrees, the positive rates of Septin 9 methylation in patients with highly differentiated, moderately differentiated and poorly differentiated CRC were 52.6% (10/19), 79.7% (59/74) and 88.9% (24/27) respectively, and the positive rate of Septin 9 methylation in peripheral blood of patients with poorly differentiated CRC was significantly higher than that of patients with highly differentiated CRC (P=0.006). The sensitivity and specificity of Septin 9 methylation in the peripheral blood were 72.3% and 92.5% respectively. Western blot results showed that the expression of Septin 9 in the exosomes of CRC patients was significantly lower than that in the normal people, while the methylation level of Septin 9 in the exosomes was significantly higher than that in the healthy people (P=0.009, 0.003). The results of this study showed that serum exosomes of CRC patients could significantly promote cell proliferation and inhibit cell apoptosis (P < 0.05 or P < 0.01).
    Conclusion Septin 9 can be used as a marker for early screening of CRC, and the mechanism of Septin 9 may be the proliferation and apoptosis resistance of CRC induced by serum exosomes in patients with CRC.

     

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