论文部分内容阅读
在有丝分裂过程中BUBR1监视微管与着丝点的结合,是保证染色体均等分离的重要分子机制之一。BUBIB变异家谱研究及其敲除模型的研究表明,BUBR1缺陷与染色体不稳定性及肿瘤的发生直接相关。近来在数种人类肿瘤,对BUBR1蛋白过度表达有所报道。但在直结肠癌,BUBR1的过度表达是否与染色体不稳定性的发生有关目前仍无定论。在人类结直肠癌的遗传不稳定性主要表现为两种类型,染色体不稳定性及微卫星不稳定性,它们提示了两条独立的肿瘤发生路径。一般认为不存在高频度微卫星不稳定性表型的肿瘤通过染色体不稳定途径癌变。P53蛋白通过多种机制对维护遗传稳定性起到重要的作用,TP53基因突变经常与染色体不稳定现象并存。DNA倍体情况也是染色体不稳定研究不可缺少的指标。本研究采用免疫组织化学法检测了一组93例进展期散发结直肠癌BUBRI蛋白的表达情况,直接测序法检测TP53变异,高分辨率荧光标记微卫星不稳定检测技术检测微卫星状态,固相激光扫描细胞仪技术检测DNA倍体情况。我们分析了BLIBR1表达与三种反映遗传背景的因子的关系。BUBR1蛋白过度表达在人结直肠癌较为常见。在非高频度微卫星不稳定的结直肠癌,BUBR1蛋白过度表达率明显为高(P<0.01),在TP53基因突变的病例其过度表达率亦较高(P<0.05)。BUBR1蛋白的过度表达与DNA异倍体无统计学相关,但DNA异倍体病例的BUBR1过度表达有偏高倾向。BUBR1表达情况与常用的,临床病理学指标无统计学相关。BUBR1过度表达同微卫星状态及TP53突变的关系明确的提示,在人类散发结直肠癌,BUBR1蛋白过度表达与染色体不稳定状态有关.BUBR1过度表达作为一种常见的分子异常,对于肿瘤的早诊预防提供新的标志物,并可能成为治疗的新靶点。
In mitosis, BUBR1 monitors the combination of microtubules with centromere and is one of the important molecular mechanisms that ensure equal chromosome segregation. BUBIB mutation genealogical studies and knockout model studies have shown that defects in BUBR1 are directly related to chromosomal instability and tumorigenesis. Recently in several human tumors, over-expression of BUBR1 protein has been reported. However, in colorectal cancer, whether the over-expression of BUBR1 is related to the occurrence of chromosomal instability is still inconclusive. Genetic instability in human colorectal cancer is mainly manifested by two types, chromosomal instability and microsatellite instability, which suggest two independent pathways of tumorigenesis. It is generally believed that cancers that do not have a high-frequency microsatellite instability phenotype are carcinogenic by means of chromosomal instability. P53 protein plays an important role in maintaining genetic stability through a variety of mechanisms. Mutations in TP53 often coexist with chromosomal instability. DNA ploidy is also an indispensable indicator of chromosomal instability. In this study, immunohistochemistry was used to detect the expression of BUBRI protein in 93 patients with advanced colorectal cancer. TP53 mutation was detected by direct sequencing and microsatellite instability was detected by high-resolution fluorescent-labeled microsatellite instability detection. Laser scanning cytometry technology to detect DNA ploidy. We analyzed the relationship between BLIBR1 expression and three factors that reflect the genetic background. BUBR1 protein overexpression is more common in human colorectal cancer. The overexpression rate of BUBR1 protein was significantly higher in non-high frequency microsatellite instability colorectal cancer (P <0.01), and higher in overexpression rate of TP53 gene mutation (P <0.05). BUBR1 protein overexpression and DNA aneuploidy was not statistically significant, but DNA aneuploidy cases of BUBR1 overexpression tended to be high. BUBR1 expression and commonly used, clinical pathological indicators were not statistically significant. The relationship between BUBR1 overexpression and microsatellite status and TP53 mutation is a clear indication that BUBR1 protein overexpression is associated with chromosomal instability in human colorectal cancer.UBB1 overexpression is a common molecular abnormality that is associated with early diagnosis of tumors Prevention offers new markers and may become a new target for treatment.