Comprehensive Analysis of the Clinical Significance of Inducing Pluripotent Stemness-Related Gene Expression in Colorectal Cancer Cells
Comprehensive Analysis of the Clinical Significance of Inducing Pluripotent Stemness-Related Gene Expression in Colorectal Cancer Cells
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DOI：
10.1245/s10434-009-0567-5
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发表时间：
2009-09-01
影响因子：
3.7
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Saiki, Yasumitsu;Ishimaru, Shinya;Mori, Masaki
背景。我们之前确定癌症干细胞样细胞可能影响结直肠癌（CRC）细胞对化疗药物的敏感性。尽管Takahashi和Park确定了正常干细胞维持所需的一组诱导多能干细胞（iPS）相关基因，但iPS相关基因表达在CRC发病机制中的确切作用仍有待确定。本研究的目的是阐明结直肠癌病例中“干性”调节基因表达的临床相关性。材料和方法。通过激光显微切割 (LMD) 从 79 例 CRC 病例的组织中切除癌细胞，并使用定量 RT-PCR 评估 iPS 相关基因 c-MYC、SOX2、OCT3/4、LIN28、KLF4 和 NANOG 的表达水平，并确定其表达与临床病理学 CRC 进展之间的任何关联。结果。我们发现 LIN28 表达与淋巴结转移 (p = 0.018) 和 Dukes 分期 (p = 0.0319) 显着相关。 SOX2表达也与淋巴结转移相关。此外，10 例 Dukes D 病病例的 SOX2 转录水平明显高于其他 69 例 (p = 0.0136)。相反，KLF4 表达与 Dukes 分期呈负相关。 c-MYC、OCT3/4 和 NANOG 的表达似乎在 CRC 病例中没有临床相关性。结论。目前的分析强烈表明，一些 iPS 相关基因的表达改变在 CRC 发病机制中发挥着作用。
Background. We previously determined that cancer stem-like cells may influence the susceptibility of colorectal cancer (CRC) cells to chemotherapeutic agents. Although Takahashi and Park identified a set of induced pluripotent stem cell (iPS)-related genes required for normal stem cell maintenance, the precise role of iPS-related gene expression in CRC pathogenesis remains to be determined. The purpose of this study was to clarify the clinical relevance of "stemness"-regulating gene expression in CRC cases.Materials and methods. Cancer cells were excised from tissues of 79 CRC cases by laser microdissection (LMD), and quantitative RT-PCR was used to evaluate expression levels of the iPS-related genes c-MYC, SOX2, OCT3/4, LIN28, KLF4, and NANOG, and to identify any associations between their expression and clinicopathological CRC progression.Results. We found that LIN28 expression is significantly associated with lymph node metastasis (p = 0.018) and Dukes stage (p = 0.0319). SOX2expression is also correlated with lymph node metastasis. Furthermore, the ten cases with Dukes D disease expressed significantly higher levels of SOX2transcript than the other 69 cases (p = 0.0136). In contrast, KLF4 expression was inversely related to Dukes stage. Expression of c-MYC, OCT3/4, and NANOG did not appear to have clinical relevance in CRC cases.Conclusion. The present analysis strongly suggests that altered expression of several iPS-related genes plays a role in CRC pathogenesis.