Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
J Surg Res. 2013 Dec;185(2):626-37. doi: 10.1016/j.jss.2013.07.014. Epub 2013 Jul 31.
The association between microsatellite instability (MSI) status and gene expression profiles in the early onset sporadic colorectal cancer (CRC) has not been clearly established. The aim of this study was to identify the altered gene expression patterns depending on the MSI status of early onset CRC and determine specific biomarkers that could provide novel therapeutic molecular targets in the Turkish population.
MSI markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were investigated in tumors from 36 early onset sporadic CRC patients in whom gene expression profiles were analyzed previously. The relationship between the gene expression profiles depending on MSI status was evaluated.
A total of 15 tumors (16.66%) were identified as having MSI and 21 tumors (58.33%) were identified as having microsatellite stability (MSS). CK20 and MAP3K8 upregulation, observed in MSS tumors, was significantly associated with lymph node metastasis, recurrence, and/or distant metastasis and a short median survival (P < 0.05). REG1A upregulation is also correlated with recurrence and/or distant metastasis and a short median survival in patients with MSI tumors (P < 0.05).
High expression levels of CK20 and MAP3K8 in MSS tumors and REG1A in MSI tumors correlated with a poor prognosis in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for the development of anticancer drugs related to MSI status for early onset CRC treatment.
微卫星不稳定性(MSI)状态与早发性散发性结直肠癌(CRC)的基因表达谱之间的关联尚未明确确立。本研究的目的是确定早发性 CRC 中根据 MSI 状态改变的基因表达模式,并确定特定的生物标志物,这些标志物可为土耳其人群提供新的治疗分子靶标。
在先前分析过基因表达谱的 36 例早发性散发性 CRC 患者的肿瘤中,研究了 MSI 标志物(BAT25、BAT26、D2S123、D5S346 和 D17S250)。评估了根据 MSI 状态的基因表达谱之间的关系。
总共鉴定出 15 个肿瘤(16.66%)为 MSI,21 个肿瘤(58.33%)为微卫星稳定(MSS)。在 MSS 肿瘤中观察到的 CK20 和 MAP3K8 的上调与淋巴结转移、复发和/或远处转移以及较短的中位生存期显著相关(P <0.05)。MSI 肿瘤中 REG1A 的上调也与复发和/或远处转移以及 MSI 肿瘤患者的较短中位生存期相关(P <0.05)。
MSS 肿瘤中 CK20 和 MAP3K8 的高表达水平以及 MSI 肿瘤中 REG1A 的高表达水平与 CRC 患者的不良预后相关。需要进一步的研究和验证;这些基因可能为与 MSI 状态相关的抗癌药物的开发提供新的治疗分子靶标,以治疗早发性 CRC。