Li Weiming, Jia Huan, Wang Jichang, Guan Hao, Li Yan, Zhang Dan, Tang Yanan, Wang Thomas D, Lu Shaoying
Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, P.R.China.
Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi Province, 710077, P.R.China.
Oncotarget. 2017 May 2;8(18):30063-30076. doi: 10.18632/oncotarget.16275.
Early diagnosis and evaluation of prognosis are both crucial for preventing poor prognosis of patients with gastric cancer (GC), a leading cause of cancer-related deaths worldwide. Cluster of differentiation 44 (CD44), an indicator of cancer stem cells, can be specifically targeted by molecular probes and detected in tissues of GC in a large quantity. In current study we found that RP-1, a specific peptide binding to CD44 protein, exhibited the potentials of specific binding to CD44 high-expressing cancer cells both in vitro and in vivo, and the capacity of predicting prognosis of human GC in a microarray assay. Results showed that RP-1 was characterized by high affinity, sensitivity and specificity, and low toxicity, suggesting RP-1 could be an ideal bio-probe for accessory diagnosis of GC. Further immunohistochemical studies and statistical analysis of tissue microarray of human GC demonstrated similar sensitivity and specificity of RP-1 with the monoclonal anti-CD44 antibody in the diagnosis of GC, and even proved that positive RP-1 could be an independent risk factor. Therefore, this study suggests RP-1 has the potentials of binding to CD44 protein expressed on the membrane of GC cells, and demonstrates the feasibility and reliability of its further application in molecular diagnosis and prognostic prediction of GC.
早期诊断和预后评估对于预防胃癌(GC)患者的不良预后均至关重要,胃癌是全球癌症相关死亡的主要原因。分化簇44(CD44)作为癌症干细胞的一个指标,可被分子探针特异性靶向,并在大量胃癌组织中检测到。在本研究中,我们发现一种与CD44蛋白结合的特异性肽RP-1在体外和体内均表现出与高表达CD44的癌细胞特异性结合的潜力,并且在微阵列分析中具有预测人类胃癌预后的能力。结果表明,RP-1具有高亲和力、敏感性和特异性以及低毒性的特点,提示RP-1可能是一种理想的胃癌辅助诊断生物探针。进一步的免疫组织化学研究以及对人类胃癌组织芯片的统计分析表明,RP-1在胃癌诊断中与抗CD44单克隆抗体具有相似的敏感性和特异性,甚至证明RP-1阳性可能是一个独立的危险因素。因此,本研究提示RP-1具有与胃癌细胞膜上表达的CD44蛋白结合的潜力,并证明了其在胃癌分子诊断和预后预测中进一步应用的可行性和可靠性。