Expression and clinical significance of Wee1 in colorectal cancer
Expression and clinical significance of Wee1 in colorectal cancer
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DOI：
10.1007/s13277-016-5081-3
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
Boye, Kjetil
中科院分区：
文献类型：
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作者：
Egeland, Eivind Valen;Flatmark, Kjersti;Boye, Kjetil
Wee 1是一种调节细胞周期进程的核激酶，已成为一种有前途的癌症治疗靶点。Wee 1的表达与某些肿瘤类型的预后不良相关，但其在结直肠癌中的预后影响和临床意义尚不清楚。通过免疫组化检测Wee 1在前瞻性收集的患者队列中的原发性结直肠癌中的表达，并研究其与临床病理参数和结局的相关性。使用细胞系RKO和SW 620进行细胞培养实验，并研究与转移促进蛋白S100 A4的关系。在分析的258个肿瘤中的229个（89%）中检测到核表达。Wee 1染色与低pT分期相关，但与人口统计学或组织病理学变量无显著相关性。与强强度和无或弱染色相比，中度Wee 1染色强度是有利的无转移和总生存率的预测因子。阳性细胞的分数不是本队列的预后因素。使用siRNA抑制Wee 1表达或用Wee 1抑制剂MK-1775治疗减少了转移促进蛋白S100 A4的表达，但在患者样本中未发现Wee 1和S100 A4之间的关系。总之，Wee 1在原发性结直肠癌中高表达，但与临床病理参数或结果的相关性不高，Wee 1表达缺乏临床意义可能表明其他肿瘤类型可能更适合进一步开发Wee 1抑制剂。
Wee1 is a nuclear kinase regulating cell cycle progression, and has emerged as a promising therapeutic target in cancer. Expression of Wee1 has been associated with poor outcome in certain tumor types, but the prognostic impact and clinical significance in colorectal cancer is unknown. The expression of Wee1 was examined by immunohistochemistry in primary colorectal carcinomas from a prospectively collected patient cohort, and associations with clinicopathological parameters and outcome were investigated. Cell culture experiments were performed using the cell lines RKO and SW620, and the relationship with the metastasis-promoting protein S100A4 was investigated. Nuclear expression was detected in 229 of the 258 tumors analyzed (89 %). Wee1 staining was associated with low pT stage, but no other significant associations with demographic or histopathological variables were found. Moderate Wee1 staining intensity was a predictor of favorable metastasis-free and overall survival compared to strong intensity and no or weak staining. The fraction of positive cells was not a prognostic factor in the present cohort. Inhibition of Wee1 expression using siRNA or treatment with the Wee1 inhibitor MK-1775 reduced expression of the metastasis-promoting protein S100A4, but no relationship between Wee1 and S100A4 was found in the patient samples. In conclusion, Wee1 is highly expressed in primary colorectal carcinomas, but few relevant associations with clinicopathological parameters or outcome were found. The lack of clinical significance of Wee1 expression could indicate that other tumor types might be better suited for further development of Wee1 inhibitors.