Yang Jia-Lin, Gupta Romi Das, Goldstein David, Crowe Philip J
Department of Surgery, Clinical School of Prince of Wales Hospital, Faculty of Medicine, University of New South Wales, Sydney 2001, Australia.
Sarcoma and Nanooncology Group, Adult Cancer Program, Lowy Cancer Research Centre, Clinical School of Prince of Wales Hospital, Faculty of Medicine, University of New South Wales, Sydney 2001, Australia.
Int J Mol Sci. 2017 May 30;18(6):1159. doi: 10.3390/ijms18061159.
: Previous studies have shown that total epidermal growth factor receptor (EGFR) protein is highly expressed in soft tissue sarcoma (STS). We aimed to investigate the significance of phosphorylated-EGFR (pEGFR) and its activated-downstream signal transducers in STS tissue samples. A tissue microarray comprising 87 STS samples was assessed for total EGFR, pEGFR and its phosphorylated signal transducers and expression was correlated with clinicopathlogical parameters including patient outcome. Although the expression of total EGFR was significantly associated with adverse STS histologic grade ( = 0.004) and clinical stage ( = 0.012) similar to pEGFR, phosphorylated protein kinase B (pAkt) and phosphorylated extracellular signal regulated kinase (pERK), it is not a prognostic factor for survival. By contrast, the expression of pEGFR is an independent factor for cancer specific survival, while pERK is an independent prognostic factor for both overall and cancer specific survival in STS ( < 0.05, Cox proportional hazard model and log-rank test) in addition to the recognised factors of tumour grade and clinical stage. pERK and pEGFR are new independent prognostic factors for overall and/or cancer specific survival in STS. The expression of EGFR/pEGFR, and their associated downstream signal transducers, was associated with STS progression, suggesting that EGFR downstream signalling pathways may jointly support STS cell survival.
以往研究表明,表皮生长因子受体(EGFR)总蛋白在软组织肉瘤(STS)中高表达。我们旨在研究磷酸化EGFR(pEGFR)及其激活的下游信号转导子在STS组织样本中的意义。对包含87个STS样本的组织微阵列进行总EGFR、pEGFR及其磷酸化信号转导子评估,并将其表达与包括患者预后在内的临床病理参数相关联。尽管总EGFR的表达与不良STS组织学分级(P = 0.004)和临床分期(P = 0.012)显著相关,与pEGFR、磷酸化蛋白激酶B(pAkt)和磷酸化细胞外信号调节激酶(pERK)相似,但它不是生存的预后因素。相比之下,pEGFR的表达是癌症特异性生存的独立因素,而pERK是STS总体生存和癌症特异性生存的独立预后因素(P < 0.05,Cox比例风险模型和对数秩检验),此外还有公认的肿瘤分级和临床分期因素。pERK和pEGFR是STS总体和/或癌症特异性生存的新独立预后因素。EGFR/pEGFR及其相关下游信号转导子的表达与STS进展相关,提示EGFR下游信号通路可能共同支持STS细胞存活。