Research Papers:

Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease

Alison K. Bauer _, Brad L. Upham, Elizabeth A. Rondini, Meredith A. Tennis, Kalpana Velmuragan and David Wiese

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Oncotarget. 2017; 8:91860-91875. https://doi.org/10.18632/oncotarget.19463

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Alison K. Bauer1, Brad L. Upham2, Elizabeth A. Rondini3, Meredith A. Tennis4, Kalpana Velmuragan1 and David Wiese5

1Department of Environmental and Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

2Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA

3Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA

4Department of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

5McLaren Regional Medical Center, Flint, MI, 48532, USA

Correspondence to:

Alison K. Bauer, email: [email protected]

Keywords: adenocarcinoma, innate immunity, non-small cell lung carcinoma, prognostic, toll-like receptor

Received: September 30, 2016    Accepted: June 02, 2017    Published: July 22, 2017


Introduction. Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients.

Results. Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype. Significant co-expression of many TLR combinations in ADC patients were also observed via RNA sequencing. Immunostaining demonstrated TLR4 and 8 significantly correlated in tumor tissue, similar to RNA.

Methods. We used kmplot.com to perform a meta-analysis on mRNA expression of TLR1-10 to determine any significant associations with OS in NSCLC and the ADC subtype. cBioportal was also used simultaneously to assess co-expression in TLR1-10 in ADC patients via RNA sequencing and to identify any molecular alterations. Lastly, immunostaining for a subset of TLRs was conducted on ADC patients.

Conclusions. Expression of innate immune receptors TLR1-10 is associated with improved survival outcomes in NSCLC. Thus, further evaluation of their predictive capacity and therapeutic utility is warranted.

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