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乳腺癌中的蛋白酪氨酸激酶7(PTK7):肿瘤表达及与临床结局相关性的回顾性分析

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome.

作者信息

Lacey Kate, Greener Megan R, Marak Tangkam R, Rakha Emad A, Green Andrew R, Ellis Ian O, Martin Stewart G, Storr Sarah J

机构信息

Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.

出版信息

Cancers (Basel). 2024 Sep 20;16(18):3206. doi: 10.3390/cancers16183206.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cacd/11430626/b33c95c45f4b/cancers-16-03206-g001.jpg

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