Abstract
Purpose The Oct4 gene plays an important role in undifferentiated embryonic stem cells and regulates stem cell pluripotency. The aim of this study was to examine the relationship between Oct4 expression and liver metastasis of colorectal cancer (CRC) in clinical samples and investigate the role and abilities of Oct4-positive CRC cells. Methods The study included 158 patients who underwent surgery for CRC between 2009 and 2011. The correlations between the Oct4 gene expression and the clinical parameters were assessed, and liver metastasis-free survival (LMFS) was evaluated in these patients. Oct4-EGFP-positive cells were established to examine their subpopulation and ability. The capacity to form liver metastasis in vivo was examined using CRC cell lines and primary cultured CRC cells. Results LMFS was significantly poor in the Oct4 high-expression group compared with the low-expression group (P = 0.008). Multivariate analyses showed that Oct4 expression (P = 0.015) and TNM stage (P < 0.001) were significantly correlated with LMFS. Oct4-EGFP-positive cells highly expressed stem cell-associated markers and had self-renewal and differentiation abilities. Oct4-high cells actively formed liver metastasis. Conclusion The Oct4 expression was correlated with liver metastasis in CRC patients. Oct4 expression cells have self-renewal and differentiation abilities like those of cancer stem cells. Oct4 contributed to forming liver metastasis in CRC.
Highlights
Cancer is a leading cause of death in Japan and developed countries, and it has become a major cause of death in developing countries [1, 2]
This study focused on the role of Oct4 in metastatic colorectal cancer (CRC), the relationship between Oct4 expression and liver metastasis of CRC in clinical samples, and the role of Oct4-expressed cells in primary cultured cells
We aimed to investigate its roles in the prognosis of metastatic CRC (mCRC) patients and reveal the stem cell-like properties of Oct4 in CRC
Summary
Cancer is a leading cause of death in Japan and developed countries, and it has become a major cause of death in developing countries [1, 2]. It is estimated that the global total number of deaths by cancer will be 9.6 million in 2018, and colorectal cancer (CRC) will be the third leading cause of cancer death (10.2% of total cancer deaths) [2]. Distant metastasis causes death in patients with CRC, and liver metastasis is most commonly found in CRC patients [3, 4]. The development of systemic combination chemotherapy has improved the prognosis. The median overall survival (OS) for patients with metastatic CRC (mCRC) is approximately 30 months [5], and the 5-year survival rate is only 19% in stage IV patients [4]. It is necessary to determine the mechanism of distant metastasis to develop treatment to improve the prognosis. Identifying the mechanism and genes responsible for liver metastasis will help to control the morbidity of CRC patients
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