Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Deng, Lei; Gyorffy, Balazs; Na, Feifei; Chen, Baoqing; Lan, Jie; Xue, Jianxin; Zhou, Lin; Lu, You
• Is Part Of: Journal of thoracic oncology. Volume 10:Issue 7(2015)
• Publication Date: 2015-07
• Subjects: Chest -- Cancer -- Periodicals; Thoracic Neoplasms -- Periodicals; 616.99494005
• DOI: 10.1097/JTO.0000000000000550
• Languages: English
• ISSNs: 1556-0864

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Introduction:</title> <p>Immune checkpoint blockade is being investigated in clinical trials and showed great potential in lung cancer. The prognostic roles of and clinicopathological factors associated with immune checkpoint gene expression, <italic>CTLA-4</italic> and <italic>PDCD1</italic> remain largely undefined, which encodes cytotoxic-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), respectively.</p> </sec> <sec> <title>Methods:</title> <p>We used a lung cancer database of 1715 patients measured by Affymetrix microarrays to analyze the association of gene expression with clinicopathological factors and survival. Hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) were calculated. Cutoffs were determined by median across the entire database.</p> </sec> <sec> <title>Results:</title> <p>In 909 patients with histology information, significantly higher <italic>PDCD1</italic> and <italic>CTLA-4</italic> expression were found in squamous carcinoma than adenocarcinoma. In 848 patients with known smoking history, current/former smokers were found to have significantly elevated gene expression compared with nonsmokers. Significant higher expression of both genes were found in TNM stage II versus I. Higher expression of <italic>PDCD1</italic> predicted worse OS in univariate analysis, but not in multivariate (HR: 1.22; 95% CI: 0.53–2.79). <italic>CTLA-4</italic> was marginally significant in univariate analysis of the entire set (HR: 1.15; 95% CI: 0.99–1.34). In patients with information for multivariate analysis, higher expression of <italic>CTLA-4</italic> was associated with worse OS (HR: 1.96; 95% CI: 1.18–3.31).</p> </sec> <sec> <title>Conclusions:</title> <p>In this study with large number of patients, <italic>PDCD1</italic> and <italic>CTLA-4</italic> expression is significantly higher in squamous carcinoma and current/former smokers. Higher expression of <italic>CTLA-4</italic>, but not <italic>PDCD1</italic> predicts worse survival.</p> </sec> </abstract>