Abstract
<div>Abstract<p><b>Purpose:</b> High inhibitor of differentiation-1 (Id1) levels have been found in some tumor types. We aimed to study Id1 levels and their prognostic impact in a large series of stages I to IV non-small cell lung cancer (NSCLC) patients. Experiments in cell lines and cells derived from malignant pleural effusions (MPE) were also carried out.</p><p><b>Experimental Design:</b> A total of 346 NSCLC samples (three different cohorts), including 65 matched nonmalignant tissues, were evaluated for Id1 expression by using immunohistochemistry. Additional data from a fourth cohort including 111 patients were obtained for Id1 mRNA expression analysis by using publicly available microarrays. <i>In vitro</i> proliferation assays were conducted to characterize the impact of Id1 on growth and treatment sensitivity.</p><p><b>Results:</b> Significantly higher Id1 protein levels were found in tumors compared with normal tissues (<i>P</i> < 0.001) and in squamous carcinomas compared with adenocarcinomas (<i>P</i> < 0.001). In radically treated stages I to III patients and stage IV patients treated with chemotherapy, higher Id1 levels were associated with a shorter disease-free survival and overall survival in adenocarcinoma patients in a log-rank test. A Cox model confirmed the independent prognostic value of Id1 levels for both stages I to III and stage IV patients. <i>In silico</i> analysis confirmed a correlation between higher Id1 mRNA levels and poor prognosis for adenocarcinoma subjects. <i>In vitro</i> Id1 silencing in radio/chemotherapy-resistant adenocarcinoma cells from MPEs restored sensitivity to both therapies.</p><p><b>Conclusions:</b> In our series, Id1 levels showed an independent prognostic value in patients with adenocarcinoma, regardless of the stage. Id1 silencing may sensitize adenocarcinoma cells to radiotherapy and chemotherapy. <i>Clin Cancer Res; 17(12); 4155–66. ©2011 AACR</i>.</p></div>
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