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

// Alison K. Bauer 1 , Brad L. Upham 2 , Elizabeth A. Rondini 3 , Meredith A. Tennis 4 , Kalpana Velmuragan 1 and David Wiese 5 1 Department of Environmental and Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 2 Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA 3 Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA 4 Department of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 5 McLaren Regional Medical Center, Flint, MI, 48532, USA Correspondence to: Alison K. Bauer, email: alison.bauer@ucdenver.edu 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 ABSTRACT 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.