J Biol Regul Homeost Agents. 2020 Nov-Dec;34(6):2059-2067. doi: 10.23812/20-293-A.


Cystatin 2 leads to a worse prognosis in patients with gastric cancer

Zhang WP#1, Wang Y#1, Tan D1, Xing CG2.

Author information

1  Department of General Surgery, Ruijin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.
2  Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
#  Contributed equally


Despite the amazing progress in the treatment of gastric cancer (GC), it is still the third leading cause of cancer death in the world. This study explored the key genes that are related to the prognosis and pathogenesis of GC. Data from the cancer genome atlas (TCGA) and Oncomine were applied to evaluate the expression of cystatin 2 (CST2) in GC samples. Kaplan-Meier plotter was carried out to detect the overall survival of GC patients with different expression levels of CST2. Gene Set Enrichment Analysis (GSEA) was carried out to investigate the functions and pathways connected with CST2 expression. Quantitative real-time polymerase chain reaction (qPCR) and Western blot assays were used to assess CST2 expression. The biological properties of GC cells were assessed with the support of cell proliferation and Transwell assays. Important proteins involved in the regulation of CST2 in GC cell behaviors were evaluated by Western blot. Through analysis of the database, we found that CST2 expression was significantly upregulated in GC samples and actively related to GC patients’ poor outcomes. Importantly, the analysis of GSEA showed that GST2 expression was closely connected with the proliferation and migration of cells, as well as the TGF-β1 signaling pathway. In addition, biological assays illustrated that over-expression of CST2 strengthened the activity and metastasis of GC cells. After the upregulation of CST2, the expression of cyclin D1, N-cadherin, vimentin, TGF-β1, and Smad4 increased, and E-cadherin expression decreased. Our findings revealed that over-expression of CST2 enhanced the growth, migration, and invasion of GC cells through modulating the epithelial-mesenchymal transition (EMT) and TGF-β1 signaling pathway, affording a possible biomarker for the treatment of GC.


CST2, E-cadherin, Smad4, TGF-β1, cyclin D1, gastric cancer

Publication type

  • Journal Article

You may also like...