Cancer 2011 Dec;117 (23): 5304-13. [IF:5.131]
Fibroblast growth factor receptor 4 regulates proliferation and antiapoptosis during gastric cancer progression.
Ye YW , Zhou Y , Yuan L , Wang CM , Du CY , Zhou XY , Zheng BQ , Cao X , Sun MH , Fu H , Shi YQ .
Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China.
复旦大学上海医学院，复旦大学上海癌症中心
Abstract
Fibroblast growth factor receptor 4 (FGFR4) belongs to the tyrosine kinase receptor family. Little is known about the effect of FGFR4 on gastric cancer (GC). Therefore, the objective of the current study was to elucidate the role of FGFR4 in the tumorigenesis and progression of GC. FGFR4 and some common prognosis markers, including p53, neu, and proliferating cell nuclear antigen (PCNA), were detected in 71 tissue samples from patients with GC using immunohistochemical analysis. In addition, a series of functional assays were carried out using small interfering RNA (siRNA) and included proliferation assays, clone assays, and apoptosis detection. Cytoplasmic FGFR4 expression in GC tissues was negative (7% of samples), low (14.1% of samples), intermediate (40.8%), and high (38% of samples). FGFR4 expression was associated with lymph node status and with PCNA and neu expression (P < .05). The 5-year relative survival rate was 61.5% in patients who had GC with low FGFR4 expression but was only 42% in patients who had high FGFR4 expression (P = .058). A subgroup analysis of the patients who had high FGFR4 expression revealed that those with stage III and IV disease had a worse prognosis (P = .044). Moreover, knockdown of FGFR4 expression led to decreased proliferation and an increased rate of apoptosis in the MKN45 and SGC7901 GC cell lines (P < .05). Western blot analysis demonstrated that the expression of caspase 3 increased, whereas the expression of extra-large B-cell lymphoma (Bcl-xL) decreased in MKN45 and SGC7901 cells after FGFR4-siRNA transfection. FGFR4 expression in GC tissue was extremely high. The current results indicated that FGFR4 may contribute to the progression of GC by regulating proliferation and antiapoptosis, indicating that FGFR4 may be a potential, novel drug target against GC. Cancer 2011;. 2011 American Cancer Society.
摘要：
一篇来自美国癌症协会的《癌症》杂志的论文揭示了成纤维细胞生长因子受体4在胃癌中的重要作用。成纤维细胞生长因子受体4 (FGFR4)属于酪氨酸激酶受体家族。目前人们对FGFR4在胃癌中影响知之甚少。因此，该研究旨在揭示FGFR4在肿瘤生成和胃癌进程中的作用。研究者们运用免疫组化检测了FGFR4和一些常见的癌症预后标志物，如p53, neu和增殖细胞核抗原(PCNA)在71例胃癌患者肿瘤组织样本中的表达。另外，他们还对其样本进行了一系列功能化的分析，如小干扰RNA(siRNA),细胞增殖实验，克隆实验以及凋亡检测。结果表明，7%的胃癌患者肿瘤组织细胞质中FGFR4的表达阴性，14.1% 的患者低表达，40.8%的患者中表达，而38%的患者高表达。FGFR4的表达与淋巴结状态以及PCNA和neu的表达相关(P < 0.05)。FGFR4低表达的胃癌患者五年相对生存率达到61.5%，而FGFR4高表达的胃癌患者仅有42%(P = 0.058)。对胃癌患者亚组分析表明处于第三和四期的患者的较差预后与 FGFR4高表达相关联 (P = 0.044)。蛋白质印记分析表明转染了FGFR4-siRNA的MKN45和 SGC7901细胞株中caspase 3的表达增加，而Bcl-xL的表达降低。FGFR4在胃癌转患者肿瘤组织中的表达显著增高。目前的结果表明FGFR4通过调控增殖和抑制凋亡来促进胃癌的进程，暗示其可以作为一个治疗胃癌的潜在的新药物靶点。
