Abstract
Purpose
To investigate the potential role of SOX2 in gastric cancer (GC) metastasis.
Methods
The SOX2 expression was detected using immunohistochemistry on a GC tissue microarray. The correlations of SOX2 expression with clinicopathological factors and 5-year survival were evaluated. To test the role of SOX2 in inhibiting GC metastasis, the cell transwell assay was performed. Real-time PCR and Western blot were used to explore the possible mechanism that SOX2 inhibits GC metastasis.
Results
In the present study, SOX2 expression was downregulated in GC tissues when compared to matching normal tissues. Moreover, patients with high SOX2 expression in cancerous tissues had less lymph node metastasis and better treatment outcome. At the subcellular level, SOX2 inhibited the GC cell migration and invasion by upregulating p21 expression. Moreover, SOX2 was determined to associate with the nuclear p21 expression. GC patients with high SOX2 and nuclear p21 expression had synergistically less lymph node metastasis and the better overall survival.
Conclusion
Our results suggest that SOX2 is a promising and favorable metastatic biomarker for GC.
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Change history
22 December 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00432-021-03863-5
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Acknowledgments
This study was funded by the Collaborative Innovation Center For Cancer Personalized Medicine; the Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment; the National Natural Science Foundation of China (Grant Number 81520108027); and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
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Informed consent was obtained from all individual participants included in the study.
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Yansu Chen and Yefei Huang have contributed equally in this study.
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Fig. S1
Representative images of SOX2 IHC staining in human gastric cancer tissues. A, negative staining; B, weak positive staining; C, moderate positive staining; D, strong positive staining. Note: original magnification, ×100 (TIFF 1062 kb)
Fig. S2
ROC curve was obtained to determine the optimal cutoff value of SOX2 expression. ROC obtained the area under the curves (AUCs) at different cutoff values of SOX2 IRS for 1, 3, and 5 years of overall survival time (TIFF 94 kb)
Fig. S3
The expression levels of SOX2 mRNA were tested in GC cell lines and a normal gastric epithelial cell GES-1 (TIFF 122 kb)
Fig. S4
The p21 expression had no effect on the SOX2 expression in BGC823 and AGS cells (TIFF 35 kb)
Fig. S5
Three shRNA-p21 plasmids were used to knock down p21 expression (TIFF 51 kb)
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Chen, Y., Huang, Y., Zhu, L. et al. SOX2 inhibits metastasis in gastric cancer. J Cancer Res Clin Oncol 142, 1221–1230 (2016). https://doi.org/10.1007/s00432-016-2125-4
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DOI: https://doi.org/10.1007/s00432-016-2125-4