Unique immune gene expression patterns in bronchoalveolar lavage and tumor adjacent non-neoplastic lung tissue in non-small cell lung cancer

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

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Background: 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. Methods: 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. Result: 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 (n = 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, p < 2 × 10-16). A 53-gene signature was determined with significant correlation with inhibitory checkpoint PDCD1 (r = 0.59, p = 0.0078) among others, where the nine top genes including IGJ and IGKC were RT-qPCR validated with high diagnostic performance (AUC: 0.920, 95% CI: 0.831-0.985, p = 2.98 × 10-7). Increased staining and expression of IGKC revealed by immunohistochemistry and immunoblotting in tumor adjacent non-neoplastic lung tissues (Wilcoxon signed-rank test, p < 0.001) and in BAL cell lysates (p < 0.01) of NSCLC, respectively, were noted. Conclusion: 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.

原文英語
文章編號232
期刊Frontiers in Immunology
9
發行號FEB
DOIs
出版狀態已發佈 - 二月 12 2018

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學

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