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C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

查看全文 作  者:Benedikte [1,2]Jacobsen;Mette Camilla [1,2]Kriegbaum;Eric Santoni-[3]Rugiu;Michael [1,2,4]Ploug 高影响力作者 机构地区:[1]The Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter, 2200 Copenhagen, Denmark;[2]Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark;[3]Department of Pathology, Diagnostic Center, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark;[4]2^(nd) Danish-Chinese Centre for Proteases and Cancer高影响力机构 出  处:《World Journal of Clinical Oncology》索引2014年第5卷第4期,共12页高影响力期刊 基  金:Supported by Copenhagen University Hospital(Rigshospitalets Forskningspuljer);The Danish National Research Foundation(Danish-Chinese Centre for Proteases and Cancer);Harboefonden,Torben og Alice Frimodts Fond,Fabrikant Einar Willumsens Mindelegat,Holger Rabitz and hustrus Legat,The Lundbeck Foundation. 摘  要:The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway. 关 键 词:LYPD3 Non-small cell lung cancer PROGNOSIS Solid growth pattern Liver kinase B1 Precursor lesions Atypical adenomatous hyperplasia METAPLASIA Squamous differentiation Ly6/Urokinase-type plasminogen activator receptor
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