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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number232
JournalFrontiers in Immunology
Volume9
Issue numberFEB
DOIs
Publication statusPublished - Feb 12 2018

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Bronchoalveolar Lavage
Non-Small Cell Lung Carcinoma
Gene Expression
Lung
Neoplasms
Immunoblotting
Immunohistochemistry
Genes
IgG Receptors
Immunoglobulin Genes
Microarray Analysis
Humoral Immunity
Nonparametric Statistics
Phagocytosis
Area Under Curve
Immunoglobulins
Immunity
Analysis of Variance
Staining and Labeling

Keywords

  • Differential expression
  • Gene expression
  • Lung cancer
  • Non-neoplastic lung tissue
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

In: Frontiers in Immunology, Vol. 9, No. FEB, 232, 12.02.2018.

Research output: Contribution to journalArticle

Kuo, CHS, Liu, CY, Pavlidis, S, Lo, YL, Wang, YW, Chen, CH, Ko, HW, Chung, FT, Lin, TY, Wang, TY, Lee, KY, Guo, YK, Wang, TH & Yang, CT 2018, 'Unique immune gene expression patterns in bronchoalveolar lavage and tumor adjacent non-neoplastic lung tissue in non-small cell lung cancer', Frontiers in Immunology, vol. 9, no. FEB, 232. https://doi.org/10.3389/fimmu.2018.00232
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. / Unique immune gene expression patterns in bronchoalveolar lavage and tumor adjacent non-neoplastic lung tissue in non-small cell lung cancer. In: Frontiers in Immunology. 2018 ; Vol. 9, No. FEB.
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AU - Liu, Chien Ying

AU - Pavlidis, Stelios

AU - Lo, Yu Lun

AU - Wang, Yen Wen

AU - Chen, Chih Hung

AU - Ko, How Wen

AU - Chung, Fu Tsai

AU - Lin, Tin Yu

AU - Wang, Tsai Yu

AU - Lee, Kang Yun

AU - Guo, Yi Ke

AU - Wang, Tzu Hao

AU - Yang, Cheng Ta

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N2 - 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.

AB - 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.

KW - Differential expression

KW - Gene expression

KW - Lung cancer

KW - Non-neoplastic lung tissue

KW - Non-small cell lung cancer

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