AUTHOR=Kuo Chih-Hsi Scott , Liu Chien-Ying , Pavlidis Stelios , Lo Yu-Lun , Wang Yen-Wen , Chen Chih-Hung , Ko How-Wen , Chung Fu-Tsai , Lin Tin-Yu , Wang Tsai-Yu , Lee Kang-Yun , Guo Yi-Ke , Wang Tzu-Hao , Yang Cheng-Ta 

TITLE=Unique Immune Gene Expression Patterns in Bronchoalveolar Lavage and Tumor Adjacent Non-Neoplastic Lung Tissue in Non-Small Cell Lung Cancer

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00232

DOI=10.3389/fimmu.2018.00232

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>The immune cells in the local environments surrounding non-small cell lung cancer (NSCLC) implicate the balance of pro- and antitumor immunity; however, their transcriptomic profiles remain poorly understood.</p></sec><sec id="ST2"><title>Methods</title><p>A transcriptomic microarray study of bronchoalveolar lavage (BAL) cells harvested from tumor-bearing lung segments was performed in a discovery group. The findings were validated (1) in published microarray datasets, (2) in an independent group by RT-qPCR, and (3) in non-diseased and tumor adjacent non-neoplastic lung tissue by immunohistochemistry and in BAL cell lysates by immunoblotting.</p></sec><sec id="ST3"><title>Result</title><p>The differential expression of 129 genes was identified in the discovery group. These genes revealed functional enrichment in Fc gamma receptor-dependent phagocytosis and circulating immunoglobulin complex among others. Microarray datasets analysis (<italic>n</italic> = 607) showed that gene expression of BAL cells of tumor-bearing lung segment was also the unique transcriptomic profile of tumor adjacent non-neoplastic lung of early stage NSCLC and a significantly gradient increase of immunoglobulin genes’ expression for non-diseased lungs, tumor adjacent non-neoplastic lungs, and tumors was identified (ANOVA, <italic>p</italic> &lt; 2 × 10<sup>−16</sup>). A 53-gene signature was determined with significant correlation with inhibitory checkpoint <italic>PDCD1</italic> (<italic>r</italic> = 0.59, <italic>p</italic> = 0.0078) among others, where the nine top genes including <italic>IGJ</italic> and <italic>IGKC</italic> were RT-qPCR validated with high diagnostic performance (AUC: 0.920, 95% CI: 0.831–0.985, <italic>p</italic> = 2.98 × 10<sup>−7</sup>). Increased staining and expression of IGKC revealed by immunohistochemistry and immunoblotting in tumor adjacent non-neoplastic lung tissues (Wilcoxon signed-rank test, <italic>p</italic> &lt; 0.001) and in BAL cell lysates (<italic>p</italic> &lt; 0.01) of NSCLC, respectively, were noted.</p></sec><sec id="ST4"><title>Conclusion</title><p>The BAL cells of tumor-bearing lung segments and tumor adjacent non-neoplastic lung tissues present a unique gene expression characterized by IGKC in relation to inhibitory checkpoints. Further study of humoral immune responses to NSCLC is warranted.</p></sec>