Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.
Future Oncol. 2013 Aug;9(8):1207-14. doi: 10.2217/fon.13.72. Epub 2013 Apr 26.
Altered α6β4 integrin expression has been demonstrated in HER-3-negative tumors and may be responsible for anti-HER treatment resistance. The current study aimed to evaluate the interaction between polymorphisms of α6 and β4 integrins and clinical outcome in HER-3-negative, K-RAS wild-type colorectal cancer patients receiving cetuximab.
PATIENTS & METHODS: K-RAS analysis was performed via direct sequencing, HER-3 was evaluated by immunohistochemistry and genotyping of α6 and β4 integrins was performed by real-time PCR.
An univariate analysis, the β4 rs8669, rs871443 and rs9367 polymorphisms correlated with progression-free and overall survival. On multivariate analysis, only the β4 rs8669 maintained an independent role in influencing progression-free survival.
We believe that β4 rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment. Our findings could also be relevant in planning future trials testing treatment strategies against the integrin-activated molecular pathways.
已证实 HER-3 阴性肿瘤中存在α6β4 整联蛋白表达改变，这可能是导致抗 HER 治疗耐药的原因。本研究旨在评估α6 和β4 整联蛋白多态性与接受西妥昔单抗治疗的 HER-3 阴性、K-RAS 野生型结直肠癌患者临床结局之间的相互关系。
通过直接测序进行 K-RAS 分析，通过免疫组织化学评估 HER-3，通过实时 PCR 进行α6 和β4 整联蛋白的基因分型。
单因素分析显示，β4 rs8669、rs871443 和 rs9367 多态性与无进展生存期和总生存期相关。多因素分析显示，只有β4 rs8669 在影响无进展生存期方面仍具有独立作用。
我们认为，β4 rs8669 基因分型可能有助于识别更有可能从抗 EGFR 治疗中获益的 HER-3 阴性、K-RAS 野生型结直肠癌患者亚组。我们的研究结果在规划针对整联蛋白激活的分子途径的治疗策略的未来试验中也可能具有相关性。
