Abstract
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.
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Acknowledgment
This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST), Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17109013, 18659384, 18390367, 18590333, 18015039, 19591509, 19390336, 20390360, 20591547, 20790961, and 20790960; the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grant-in-Aid for Scientific Research on Priority Areas, grant number 18015039; Third-Term Comprehensive Ten-Year Strategy for Cancer Control, grant number 16271201 and NEDO (New Energy and Industrial Technology Development Organization) Technological Development for Chromosome Analysis.
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Saiki, Y., Ishimaru, S., Mimori, K. et al. Comprehensive Analysis of the Clinical Significance of Inducing Pluripotent Stemness-Related Gene Expression in Colorectal Cancer Cells. Ann Surg Oncol 16, 2638–2644 (2009). https://doi.org/10.1245/s10434-009-0567-5
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DOI: https://doi.org/10.1245/s10434-009-0567-5