Lung cancer is the leading cause of cancer death worldwide and global burden could be reduced through targeted application of chemoprevention. The development of squamous lung carcinoma has been linked with persistent, high-grade bronchial dysplasia. Bronchial histology improved in former smokers in a chemoprevention trial with the prostacyclin analogue iloprost. Prostacyclin acts through peroxisome proliferator-activated receptor gamma (PPARγ) to reverse epithelial to mesenchymal transition and promote anticancer signaling. We hypothesized that the prostacyclin signaling pathway and EMT could provide response markers for prostacyclin chemoprevention of lung cancer. Human bronchial epithelial cells were treated with cigarette smoke condensate (CSC) or iloprost for 2 weeks, CSC for 16 weeks, or CSC for 4 weeks followed by 4 weeks of CSC and/or iloprost, and RNA was extracted. Wild-type or prostacyclin synthase transgenic mice were exposed to 1 week of cigarette smoke or one injection of urethane, and RNA was extracted from the lungs. We measured potential markers of prostacyclin and iloprost efficacy in these models. We identified a panel of markers altered by tobacco carcinogens and inversely affected by prostacyclin, including γ, These data introduce a panel of potential markers for monitoring interception of bronchial dysplasia progression during chemoprevention with prostacyclin. Chemoprevention is a promising approach to reduce lung cancer mortality in a high-risk population. Identifying markers for targeted use is critical for success in future clinical trials of prostacyclin for lung cancer chemoprevention. .

Background Excessive alcohol use is a leading etiology of liver disease and indication for liver transplantation. Accurate measurement of alcohol use remains a challenge in the management of patients in the pre‐, peri‐, and post‐liver transplant settings. Blood 16:0‐18:1 phosphatidylethanol (PEth) concentration is a sensitive and specific biomarker of binge and moderate, chronic alcohol use. As PEth has the longest detection window of available blood‐based direct alcohol biomarkers for moderate to heavy drinking, it shows promise as an indicator of patterns and chronicity of drinking. However, the utility of PEth in clinical liver transplantation is understudied. This study examines the association of PEth results with liver transplantation waitlist‐focused patient outcomes. Methods Retrospective data for all patients tested for PEth for a one‐year period at a tertiary care medical center with an active liver transplantation program were abstracted. Indications for PEth testing, liver transplantation waitlist‐related outcomes (e.g., listing and delisting) following testing and associations of PEth results with other parameters were analyzed. Results Over a one‐year period, 153 PEth tests were performed on 109 individuals. The most frequent indications for PEth testing were as an objective indicator of alcohol use patterns (86.3%) and to assess alcohol as a putative etiology of liver injury (13.7%). Of the 109 patients, 56 were medically appropriate for liver transplantation. Medically acceptable candidates with unfavorable transplantation waitlist‐related outcomes (delisting, deferment of transplant evaluation, deferment of listing until completion of recommended alcohol rehabilitation, and being deemed not a transplant candidate) were at least 3.41 times more likely to have a positive PEth test than those with favorable transplantation waitlist‐related outcomes (odds ratio 3.41, confidence interval 3.41 to ∞, p = 0.001). Conclusion This single‐center study reporting a comprehensive account of PEth utilization at a liver transplant center demonstrates that liver transplantation waitlist‐related outcomes are associated with PEth test results. Patients with positive PEth tests were more likely to have unfavorable transplant waitlist‐related outcomes. PEth testing has not been validated as a predictor of relapse to drinking in post‐transplant patients and because its utility in the pre‐transplant setting is unclear its use could lead to disparities in the selection of patients for liver transplantation.

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