Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.

BackgroundMinority patients and those from low socioeconomic backgrounds are faced with barriers to care regarding breast reconstruction. With this study, we seek to elucidate variances in demographics to determine predictors of complications in implant-based breast reconstruction.MethodsPatients who underwent breast reconstruction with either direct to implant or immediate expander reconstruction by 1 surgeon were identified using the preoperative Breast-Q.Current income statistics available from the US Census Bureau by self-reported zip code were used to determine the median household income (MHI) to stratify differing socioeconomic backgrounds. Demographics were compared with body mass index, comorbidities, overall rate of postoperative complications, rate of implant infection, and type of reconstruction.ResultsTwo hundred ninety-five patients met inclusion criteria. Overall rate of complications and rate of breast implant infection was higher for MHI of less than $50,000 compared with greater than $50,000 (P = 0.043 overall complications 40.20% vs 28.8%) (P = 0.04 implant infection 14.4% vs 7.1%). African American patients had higher body mass index (P = <0.001), rates of HTN (P = <0.001), and diabetes (P = 0.001), and were more likely to have a lower income (P = <0.001). There was, however, no difference in overall complications (P = 0.26), implant infection rate (P = 0.994), or capsular contracture (0.367) based on race. There was no difference in rate of comorbidities between low and high socioeconomic areas.ConclusionThis cohort demonstrates a higher rate of overall complications and infection in patients with a lower MHI and no difference based on race despite having higher risk factors for complications.Socioeconomic status is a multifaceted barrier to care that must be addressed in the perioperative period to decrease breast implant associated complications.

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