UC San Diego

Although many of the mechanisms induced by cigarette smoke are highly conserved in cancers in general, the use of new genomic and transcriptomic data analysis tools suggests that some mechanisms underlying smoking induced cancers may be unique. This project aims to elucidate connections between smoking-associated cancers and novel immune-associated (IA) mechanisms underlying smoking-induced carcinogenesis, with an emphasis on IA gene expression and microRNA (miRNA) activity. We investigated a total of 5 cancers whose incidence is known to be well-correlated with smoking. Patient whole genome sequencing, miRNA sequencing, and clinical variable data was downloaded from The Cancer Genome Atlas (TCGA) and was analyzed computationally. We found little overlap between survival-corelated immune-associated genes dysregulated in each of the 5 cancers studied. However, further downstream analysis suggested the potential importance of a select few genes. One of these genes is osteopontin (OPN), which was upregulated in HNSCC and ESCA patients alongside key oncogene upregulation, tumor suppressor downregulation, and mutation presence. Dysregulation of TNF-related genes was unique between HNSCC and LUSC samples, suggesting that smoking causes different behavior of TNF depending on the cancer type or tumor site. Analysis of microRNA expression indicated that survival-correlated IA genes were likely unaffected by miRNA expression. These findings indicate the presence of common and unique patterns of IA gene dysregulation between smoking-mediated cancers that may be used for future therapeutic strategies.