Zuo L, Wang L, Yang Z, Li J, Wang W, Li J, Wang Y, Song X, Zhnag X, Geng Z
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu 233030, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Sep 20;43(9):1460-1468. doi: 10.12122/j.issn.1673-4254.2023.09.02.
To investigate the expression of calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) in gastric cancer and its effect on gastric cancer cell invasion and metastasis.
The association of CAMSAP2 expression levels with progression and prognosis of gastric cancer was analyzed using public cancer data and in 106 patients receiving radical gastrectomy in our hospital from October, 2013 to October, 2017. The biological functions of CAMSAP2 were predicted using bioinformatics analysis. Gastric cancer MGC803 cells with CAMSAP2 overexpression and knockdown were observed for epithelial-mesenchymal transition (EMT), migration and invasion. A nude mouse model bearing orthotopic gastric cancer cell xenografts was established for verifying the results and exploring the underlying molecular mechanism.
Gastric cancer tissues expressed high levels of CAMSAP2, which were positively correlated with CEA and CA19-9 (<0.001). Cox regression analysis showed that CAMSAP2 expression level was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR=2.969, 95% : 1.031-8.548). Enrichment analysis suggested that CAMSAP2 was involved in epithelialmesenchymal transition (EMT) and TGF-β signaling. In gastric cancer cells, CAMSAP2 overexpression significantly increased the expressions of vimentin and N-cadherin, inhibited the expression of E-cadherin, and enhanced cell migration and invasion (<0.05); CAMSAP2 knockdown produced the opposite effects in the cells (<0.05). In the tumor- bearing mice, xenografts overexpressing CAMSAP2 showed enhanced metastasis (<0.05), increased vimentin and N-cadherin expressions and lowered E-cadherin expression (<0.05), and the xenografts with CAMSAP2 knockdown showed the opposite changes (<0.05). Both the and experiments showed that CAMSAP2 overexpression increased and CAMSAP2 knockdown lowered the levels of TGF-β and p-Smad2/3 in the gastric cancer cells (<0.05).
The high expression of CAMSAP2 contributes to disease progression and poor prognosis of gastric cancer possibly by upregulating TGF-β signaling to promote EMT.
探讨钙调蛋白调节的血影蛋白相关蛋白2（CAMSAP2）在胃癌中的表达及其对胃癌细胞侵袭和转移的影响。
利用公开的癌症数据以及2013年10月至2017年10月在我院接受根治性胃切除术的106例患者，分析CAMSAP2表达水平与胃癌进展及预后的相关性。通过生物信息学分析预测CAMSAP2的生物学功能。观察过表达和敲低CAMSAP2的胃癌MGC803细胞的上皮-间质转化（EMT）、迁移和侵袭情况。建立原位胃癌细胞异种移植裸鼠模型以验证结果并探索潜在的分子机制。
胃癌组织中CAMSAP2表达水平较高，与癌胚抗原（CEA）和糖类抗原19-9（CA19-9）呈正相关（<0.001）。Cox回归分析显示，CAMSAP2表达水平是影响胃癌患者5年生存率的独立危险因素（风险比[HR]=2.969，95%置信区间：1.031 - 8.548）。富集分析表明，CAMSAP2参与上皮-间质转化（EMT）和转化生长因子-β（TGF-β）信号传导。在胃癌细胞中，过表达CAMSAP2显著增加波形蛋白和N-钙黏蛋白的表达，抑制E-钙黏蛋白的表达，并增强细胞迁移和侵袭能力（<0.05）；敲低CAMSAP2则在细胞中产生相反的作用（<0.05）。在荷瘤小鼠中，过表达CAMSAP2的异种移植瘤显示转移增强（<0.05），波形蛋白和N-钙黏蛋白表达增加，E-钙黏蛋白表达降低（<0.05），而敲低CAMSAP2的异种移植瘤则出现相反的变化（<0.05）。体外和体内实验均表明，过表达CAMSAP2会增加胃癌细胞中TGF-β和磷酸化Smad2/3的水平，敲低CAMSAP2则降低其水平（<0.05）。
CAMSAP2的高表达可能通过上调TGF-β信号传导促进EMT，从而导致胃癌疾病进展和预后不良。
