From such results, it can be concluded that the positive expressions of CD133 mRNA and CD133 AUY-922 protein positively related to the lymphatic metastasis in GC, which can reasonably be considered as a risk factor to lymphatic metastasis and tumor invasion. Hence, the strategies aimed at the CD133 and SDF-1/CXCR4 modulating axis,
and the molecular pathway for lymphatic metastasis may have important clinical significances to inhibit metastasis of CSCs. Ki-67 is a kind of nuclear protein, which expresses in cellular cycle of G1, S, G2 and M phases, but not in G0 phase. In order to probe the relation of CD133 expression with the proliferation of tumor cells with or without CD133 positivity, the CD133 mRNA expressive level was applied in this study due to the rare CSCs (usually around 1%-5% of total tumor cells) with CD133 protein positivity in tumor as common and the difficulty to identify CSCs as immature tumor cells from matured tumor cells morphologically. From PARP inhibitors clinical trials current limited information indicated in this investigation of ours, there occurred the significantly higher expression of CD133 mRNA in subgroup with lower Ki-67 LI in comparison with that in subgroup with higher Ki-67 LI. Theoretically, this phenomenon
observed in our study could be elucidated as the various biological profiles in different stage of tumor differential process or in proliferating characterization in the early stage of carcinogenesis and tumor development. And this proliferating characterization would be gradually weakened in tumor development probably. Additionally, in some extent, this higher expression of CD133 mRNA in subgroup with lower Ki-67 LI could also be explained to the resistant potential of CSCs to
anti-cancerous therapy because tumor cells in Phase G0 such as most of CSCs were difficult to be killed by cytotoxin drugs and radiotherapy [18]. On the other hand, for other explanation of this interesting phenomenon with negative relation between CD133 mRNA and Ki-67 LI, as our consideration, it is also contributed to the different proliferating abilities of ADAMTS5 matured tumor cells and immature tumor cells of CD133 positivity with some characteristics of CSCs. As well known, CSCs possessed strong differentiation proficiency, but this proficiency might not mean strong proliferating ability, especially comparing with that of matured tumor cells with CD133 negative expression probably. As there occurred so many kinds of cells in primary lesion and the limitation of only morphological and immunohistochemical observations in this study, the investigation on the both expressions of CD133 and Ki-67 in the same tumor cells should be necessarily considered to carry out in future.
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