SASS6 overexpression is associated with mitotic chromosomal abnormalities and a poor prognosis in patients with colorectal cancer.
SASS6 overexpression is associated with mitotic chromosomal abnormalities and a poor prognosis in patients with colorectal cancer.
复制标题
DOI：
10.3892/or.2015.4014
复制
发表时间：
2015-08
期刊：
影响因子：
4.2
通讯作者：
K. Shinmura;Hisami Kato;Y. Kawanishi;K. Nagura;T. Kamo;Y. Okubo;Y. Inoue;Nobuya Kurabe;Chunping Du-C
中科院分区：
文献类型：
--
作者：
K. Shinmura;Hisami Kato;Y. Kawanishi;K. Nagura;T. Kamo;Y. Okubo;Y. Inoue;Nobuya Kurabe;Chunping Du-C
纺锤体组装异常蛋白6同源物（SASS 6）在中心粒复制调控中起重要作用。迄今为止，SASS 6的遗传改变尚未在人类癌症中报道。在本研究中，我们研究了SASS 6表达是否在结直肠癌（CRC）中受到异常调节。SASS 6 mRNA和蛋白表达水平分别在81例原发性CRC中的49例（60.5%）和19例原发性CRC中的11例（57.9%）中观察到增加。SASS 6 mRNA表达上调有统计学意义（P=0.0410）。接下来，使用诱导性表达SASS 6的DLD-1结肠癌细胞，显示SASS 6过表达诱导中心体扩增、有丝分裂异常（如染色体错配和落后染色体）和染色体数目变化。SASS 6的过度表达与有丝分裂后期桥的形成有关（P<0.01）。癌症基因组图谱（TCGA）数据中也显示了结肠癌中SASS 6的上调，并且被证明是生存不良的独立预测因子（多变量分析：风险比，2.805; 95%置信区间，1.244 - 7.512; P=0.0112）。最后，对TCGA数据的进一步分析表明，SASS 6在除结肠癌以外的11种癌症类型中的8种中以适度的方式上调，并且发现SASS 6上调与肾细胞癌和肺腺癌患者的不良生存结果相关。我们目前的研究结果表明，SASS 6表达的上调参与了CRC的发病机制，并与结肠癌患者的预后不良有关。他们还表明，SASS 6上调是人类癌症中相对常见的遗传异常。
Spindle assembly abnormal protein 6 homolog (SASS6) plays an important role in the regulation of centriole duplication. To date, the genetic alteration of SASS6 has not been reported in human cancers. In the present study, we examined whether SASS6 expression is abnormally regulated in colorectal cancers (CRCs). Increased SASS6 mRNA and protein expression levels were observed in 49 (60.5%) of the 81 primary CRCs and 11 (57.9%) of the 19 primary CRCs, respectively. Moreover, the upregulation of SASS6 mRNA expression was statistically significant (P=0.0410). Next, using DLD-1 colon cancer cells inducibly expressing SASS6, SASS6 overexpression was shown to induce centrosome amplification, mitotic abnormalities such as chromosomal misalignment and lagging chromosome, and chromosomal numerical changes. Furthermore, SASS6 overexpression was associated with anaphase bridge formation, a type of mitotic structural abnormality, in primary CRCs (P<0.01). SASS6 upregulation in colon cancer was also revealed in the Cancer Genome Atlas (TCGA) data and was shown to be an independent predictor of poor survival (multivariate analysis: hazard ratio, 2.805; 95% confidence interval, 1.244‑7.512; P=0.0112). Finally, further analysis of the TCGA data demonstrated SASS6 upregulation in a modest manner in 8 of 11 cancer types other than colon cancer, and SASS6 upregulation was found to be associated with a poor survival outcome in patients with kidney renal cell carcinoma and lung adenocarcinoma. Our present findings revealed that the upregulation of SASS6 expression is involved in the pathogenesis of CRC and is associated with a poor prognosis among patients with colon cancer. They also suggest that SASS6 upregulation is a genetic abnormality relatively common in human cancer.