Ge Xiao-Chuan, Wu Fan, Li Wei-Tao, Zhu Xuan-Jin, Liu Jian-Wei, Wang Bai-Lin
Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, Guangdong 510220, P.R. China.
Oncol Lett. 2017 Jun;13(6):4341-4348. doi: 10.3892/ol.2017.5984. Epub 2017 Apr 4.
WEE1 is a serine/threonine protein kinase that inactivates cell division cycle 2 and is therefore a critical cell cycle regulator. Increased WEE1 expression has been observed in numerous types of human malignancies, including hepatocellular carcinoma and melanoma. WEE1 inhibition also results in evident anti-tumor effects in several human tumor cells including colon cancer cells, suggesting WEE1 as a potential therapeutic target for the treatment of cancer. However, the expression pattern of WEE1 in colorectal cancer (CRC) remains unclear. In the present study, WEE1 mRNA expression in 43 cases of CRC tissues matched with adjacent normal tissues was determined by reverse-transcription quantitative polymerase chain reaction. The results demonstrated that WEE1 mRNA expression was significantly increased in CRC tissues and that this upregulation correlated significantly with hepatic metastasis, distant metastasis and high tumor node metastasis (TNM) stage of CRC. Additionally, WEE1 protein in 102 CRC tissue samples was detected by immunohistochemistry, and positive staining of WEE1 was identified in more than half of patients with CRC. WEE1 staining scores were also observed to be associated with distant metastasis and high TNM stage of CRC. In addition, patients with CRC with high WEE1 staining score (2+ or 3+) exhibited either poorer overall survival or poorer disease-free survival compared with those with low WEE1 staining score (0 or 1+). The multivariable Cox model also identified a high WEE1 staining score as well as high TNM stage to be independent prognostic factors for CRC. In conclusion, WEE1 upregulation is associated with a high degree of malignancy and poor prognosis of CRC, suggesting WEE1 as a potential prognostic biomarker for CRC.
WEE1是一种丝氨酸/苏氨酸蛋白激酶,可使细胞分裂周期2失活,因此是一种关键的细胞周期调节因子。在包括肝细胞癌和黑色素瘤在内的多种人类恶性肿瘤中均观察到WEE1表达增加。WEE1抑制在包括结肠癌细胞在内的几种人类肿瘤细胞中也产生明显的抗肿瘤作用,这表明WEE1是治疗癌症的潜在治疗靶点。然而,WEE1在结直肠癌(CRC)中的表达模式仍不清楚。在本研究中,通过逆转录定量聚合酶链反应测定了43例CRC组织及其配对的相邻正常组织中WEE1 mRNA的表达。结果表明,CRC组织中WEE1 mRNA表达显著增加,且这种上调与CRC的肝转移、远处转移和高肿瘤淋巴结转移(TNM)分期显著相关。此外,通过免疫组织化学检测了102例CRC组织样本中的WEE1蛋白,超过一半的CRC患者中发现WEE1呈阳性染色。还观察到WEE1染色评分与CRC的远处转移和高TNM分期相关。此外,与WEE1染色评分低(0或1+)的患者相比,WEE1染色评分高(2+或3+)的CRC患者的总生存期或无病生存期较差。多变量Cox模型也确定高WEE1染色评分以及高TNM分期是CRC的独立预后因素。总之,WEE1上调与CRC的高度恶性和不良预后相关,提示WEE1作为CRC潜在的预后生物标志物。