结直肠癌中RAC3表达水平及其对FOLFOX方案疗效的影响

Expression of RAC3 in colorectal cancer and its efficacy in FOLFOX chemotherapeutic response

目的探讨受体相关共激酶3(RAC3)在结直肠癌(CRC)组织中的表达水平及CRC患者对亚叶酸钙联合氟尿嘧啶、奥沙利铂(FOLFOX)方案敏感性的影响。方法采用荧光实时定量PCR (qRT-PCR)检测48对CRC临床组织标本中RAC3的表达水平,采用χ~2检验分析其表达水平与临床病理特征之间的关系。运用免疫组化法检测125例初次评估无法手术切除且行术前新辅助化疗(FOLFOX方案)2～3个月的CRC患者的RAC3蛋白表达水平,获检组织标本由结/直肠镜活检获得,并为病理证实为CRC。回顾性分析RAC3表达水平与CRC患者对FOLFOX方案治疗反应的相关性。结果 qRT-PCR显示CRC组织中RAC3水平明显高于癌旁正常黏膜上皮组织(P<0.01);其表达水平与肿瘤较晚分期(P=0.041)、微血管侵犯(P=0.014)、淋巴结转移(P=0.030)相关。Kaplan-Meier生存分析显示RAC3表达增高的CRC患者术后总体生存期(OS)缩短。免疫组化显示RAC3蛋白的阳性表达率显著高于正常黏膜上皮组织,且RAC3蛋白阳性表达的CRC患者对FOLFOX方案敏感性低于RAC3蛋白阴性表达者(P<0.05)。结论 RAC3在CRC组织中表达明显升高,并与CRC患者对FOLFOX化疗方案的临床反应有关,可能是CRC精准治疗策略中一个潜在的生物标志物。

Objective To investigate the expression and its efficacy in predicting FOLFOX chemosensitivity of receptor associated-coactivator 3 (RAC3) in colorectal cancer(CRC). Methods Forty-eight paired clinical samples and clinicopathologic characteristics were analyzed. Quantitative real-time PCR (qRT-PCR) analysis was used to evaluate expression levels of RAC3 in colorectal cancer tissues. Immunohistochemical method was used to explore the expression of RAC3 protein in 125 cases of exploratory biopsies. Results RAC3 was up-regulated in CRC tissues compared with adjacent mucosa ( P <0.01),and its expression level was significantly correlated with TNM stage,vascular invasion and lymph node metastasis ( P <0.05). The Kaplan-Meier plot in TCGA database showed that the median survival period in the CRC patients with high RAC3 expression level was shorter than the low expression subgroup.Positive expression of RAC3 protein CRC patients had lower sensitivity to FOLFOX regimen than negative expression of RAC3 protein (Folic acid-5-fluorouracil and oxaliplatin). Conclusion RAC3 is up-regulated in CRC tissues and its expression level is significantly correlated with unfavorable prognosis. In addition,RAC3 possesses the potential to be a predictive marker for CRC prognosis and chemotherapeutic response.