RESUMO
BACKGROUND: Although evidence regarding pituitary tumor-transforming 3, pseudogene (PTTG3P) involvement in human cancers has been acquired via human and animal model-based molecular studies, there is a lack of pan-cancer analysis of this gene in human tumors. METHODS: Tumor-causing effects of PTTG3P in 24 human tumors were explored using The Cancer Genome Atlas (TCGA) datasets from different bioinformatics databases and applying in silico tools such as The University of ALabama at Birmingham CANcer (UALCAN), Human Protein Atlas (HPA), Kaplan Meier (KM) plotter, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Tumor IMmune Estimation Resource (TIMER), and Comparative Toxicogenomics Database (CTD). Then, via in vitro experiments, including RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq), expression and promoter methylation levels of PTTG3P were verified in cell lines. RESULTS: The PTTG3P expression was overexpressed across 23 malignancies and its overexpression was further found significantly effecting the overall survival (OS) durations of the esophageal carcinoma (ESCA) and head and neck cancer (HNSC) patients. This important information helps us to understand that PTTG3P plays a significant role in the development and progression of ESCA and HNSC. As for PTTG3P functional mechanisms, this gene along with its other binding partners was significantly concentrated in "Oocyte meiosis", "Cell cycle", "Ubiquitin mediated proteolysis", and "Progesterone-mediated oocyte maturation". Moreover, ESCA and HNSC tissues having the higher expression of PTTG3P were found to have lower promoter methylation levels of PTTG3P and higher CD8+ T immune cells level. Additionally, PTTG3P expression-regulatory drugs were also explored in the current manuscript for designing appropriate treatment strategies for ESCA and HNSC with respect to PTTG3P expression. CONCLUSION: Our pan-cancer based findings provided a comprehensive account of the oncogenic role and utilization of PTTG3P as a novel molecular biomarker of ESCA and HNSC.
RESUMO
BACKGROUND: Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion. METHOD: We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer's name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria. RESULTS: Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer's name and retail price on cigarette packs as the most relevant criteria to detect tax evasion. CONCLUSIONS: One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.
