Lacey Kate, Greener Megan R, Marak Tangkam R, Rakha Emad A, Green Andrew R, Ellis Ian O, Martin Stewart G, Storr Sarah J
Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
Cancers (Basel). 2024 Sep 20;16(18):3206. doi: 10.3390/cancers16183206.
Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry. In addition, mRNA expression in the METABRIC (n = 1980) and the TCGA breast cancer cohorts (n = 1082) was evaluated. Associations between PTK7 expression and clinicopathological criteria and patient outcome were determined. No association between PTK7 protein expression and breast cancer-specific survival was observed; however, mRNA expression in the METABRIC cohort was associated with breast cancer-specific survival ( < 0.001). PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.
蛋白酪氨酸激酶7(PTK7),最初被称为结肠癌激酶(CCK4),是一种进化保守的、催化缺陷的跨膜受体,参与Wnt信号传导。PTK7已被确定为一个潜在的治疗靶点,一种PTK7抗体药物偶联物(PF-06647020;考非妥珠单抗佩利多特)已在三阴性乳腺癌、卵巢癌和非小细胞肺癌的I期临床试验中进行了研究。通过免疫组织化学对1136例早期浸润性乳腺肿瘤中的PTK7蛋白表达进行了评估。此外,还评估了METABRIC队列(n = 1980)和TCGA乳腺癌队列(n = 1082)中的mRNA表达。确定了PTK7表达与临床病理标准及患者预后之间的关联。未观察到PTK7蛋白表达与乳腺癌特异性生存率之间的关联;然而,METABRIC队列中的mRNA表达与乳腺癌特异性生存率相关(<0.001)。PTK7蛋白和mRNA表达分别与预后较差的诺丁汉预后指数(NPI)和中度预后NPI的患者的乳腺癌特异性生存率相关。综上所述,这些数据表明PTK7表达与乳腺癌患者亚组的患者预后相关。