ABSTRACT
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.
ABSTRACT
OBJECTIVES: Prominin 2 (PROM2) gene has been reported as a molecular biomarker of human cancers; however, its role is still controversial. This study was therefore arranged to seek the role of PROM2 in different cancers with Bioinformatics and in vitro analyses. METHODS: A combination of bioinformatics and molecular experiments. RESULTS: Through the utilization of Bioinformatics analysis, it was observed that in 19 out of the 24 human cancers studied, there was a significant increase in the expression of PROM2 compared to the respective control samples. Additionally, the overexpression of PROM2 was linked specifically to a decrease in overall survival (OS) among breast cancer (BRCA), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC) patients. Furthermore, advanced molecular investigations were conducted, encompassing RNA sequencing (RNA-seq) as well as targeted bisulfite sequencing (bisulfite-seq) assessments of PROM2. These analyses were performed across an array of lung cancer cell lines (A549, ABC-1, EBC-1, and LK-2) and a normal control lung cell line (MRC-9). Results of these analysis revealed overexpression and reduced methylation of PROM2 within lung cancer cell lines, relative to the corresponding control cell line. This suggests that PROM2 assumes a substantial function in the advancement and course of BRCA, LUAD, and UCEC cancers. Subsequent pathway analysis revealed that genes enriched by PROM2 are actively engaged in four pivotal pathways. Additionally, intriguing associations were observed between PROM2 expression, tumor purity, infiltration of CD8+ T immune cells, and genetic modifications. Moreover, we also predicted a few MicroRNAs (miRNAs), transcription factors (TFs), and potential drugs that could help to understand and better manage these cancers via designing appropriate therapies targeting PROM2. CONCLUSION: Via this study, we effectively revealed PROM2 overexpression as a potential diagnostic and prognostic biomarker of survival in BRCA, LUAD, and UCEC.
