Lin Qi, Wei Ye, Zhong Yunshi, Zhu Dexiang, Ren Li, Xu Pingping, Zheng Peng, Feng Qingyang, Ji Meiling, Lv Minzhi, Liang Chunmin, Xu Jianmin
Department of General Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
Tumour Biol. 2014 Oct;35(10):9743-50. doi: 10.1007/s13277-014-2267-4. Epub 2014 Jun 28.
There are currently no accurate predictive markers of metachronous liver metastasis from colorectal cancer. Recent studies demonstrated that the expression patterns of sphingosine-1-phosphate receptor 1 (S1PR1) are altered in several tumors, but in colorectal cancer, the patterns remain unknown. Our study was designed to evaluate the expression and prognostic significance of S1PR1 protein in patients with colorectal cancer. The expression of S1PR1 was detected using the tissue microarray technique and immunohistochemical method and compared with clinicopathological parameters in 153 colorectal cancer patients. The prognostic value of S1PR1 expression was evaluated by Kaplan-Meier and Cox regression analysis. A molecular prognostic stratification scheme incorporating S1PR1 expression was determined by using receiver operating characteristic (ROC) analysis. S1PR1 was significantly highly expressed in 70.6 % (108/153) of the colorectal cancer lesions compared to their high expressions in only 5.9 % (9/153) of the adjacent non-cancerous tissues. Upregulated expression of S1PR1 was significantly associated with depth invasion and metachronous liver metastasis. Increased S1PR1 expression in colorectal cancer was positively correlated with poor overall survival. Multivariate survival analysis suggested that S1PR1 expression was an independent prognostic indicator for the disease. Applying the prognostic value of S1PR1 density to TNM stage system showed a better prognostic value in patients with colorectal cancer. Aberrant S1PR1 expression in colorectal cancer was associated with metachronous liver metastasis and worse survival outcome, and also, it was an independent prognostic factor. According to our analysis, combined TNM stage and intratumoral expression of S1PR1 demonstrated a better prognostic value than any of these two parameters alone. Conclusively, we suggest that detection and analysis of S1PR1 expression in colorectal cancer tissue might be used for predicting prognosis of colorectal cancer.
目前尚无准确预测结直肠癌异时性肝转移的标志物。最近的研究表明，鞘氨醇-1-磷酸受体1（S1PR1）的表达模式在几种肿瘤中发生改变，但在结直肠癌中，其模式仍不清楚。我们的研究旨在评估S1PR1蛋白在结直肠癌患者中的表达及预后意义。采用组织芯片技术和免疫组化方法检测153例结直肠癌患者S1PR1的表达，并与临床病理参数进行比较。通过Kaplan-Meier法和Cox回归分析评估S1PR1表达的预后价值。利用受试者工作特征（ROC）分析确定了包含S1PR1表达的分子预后分层方案。与仅5.9%（9/153）的癌旁非癌组织高表达相比，70.6%（108/153）的结直肠癌病灶中S1PR1显著高表达。S1PR1表达上调与深度浸润和异时性肝转移显著相关。结直肠癌中S1PR1表达增加与总体生存率差呈正相关。多因素生存分析表明，S1PR1表达是该疾病的独立预后指标。将S1PR1密度的预后价值应用于TNM分期系统显示，对结直肠癌患者具有更好的预后价值。结直肠癌中S1PR1异常表达与异时性肝转移及更差的生存结局相关，且是独立的预后因素。根据我们的分析，联合TNM分期和肿瘤内S1PR1表达比这两个参数单独使用具有更好的预后价值。总之，我们建议检测和分析结直肠癌组织中S1PR1表达可用于预测结直肠癌的预后。
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