Screening a novel six critical gene-based system of diagnostic and prognostic biomarkers in prostate adenocarcinoma patients with different clinical variables

Hadia Munir; Fawad Ahmad; Sajid Ullah; Saeedah Musaed Almutairi; Samra Asghar; Tehmina Siddique; Mostafa A Abdel-Maksoud; Rabab Ahmed Rasheed; Fatma Alzahraa A Elkhamisy; Mohammed Aufy; Hamid Yaz

Screening a novel six critical gene-based system of diagnostic and prognostic biomarkers in prostate adenocarcinoma patients with different clinical variables

Am J Transl Res. 2022 Jun 15;14(6):3658-3682. eCollection 2022.

Authors

Affiliations

¹ Akhtar Saeed Medical and Dental College Pakistan.
² Rural Health Center Manthar Rahim Yar Khan, Pakistan.
³ Cardiac ICU Medikay Cardiac Center Park Road Islamabad Islamabad 4400, Pakistan.
⁴ Department of Botany and Microbiology, College of Science, King Saud University Riyadh, P.O. 2455, Riyadh 11451, Saudi Arabia.
⁵ Department of Medical Laboratory Technology, Faculty of Rehablitation and Allied Health Sciences, Riphah International University Faisalabad, Faisalabad, Pakistan.
⁶ Department of Biotechnology, Faculty of Life Sciences, University of Okara Okara, Pakistan.
⁷ Histology and Cell Biology Department, Faculty of Medicine, King Salman International University South Sinai, Egypt.
⁸ Pathology Department, Faculty of Medicine, Helwan University Cairo, Egypt.
⁹ Basic Medical Sciences Department, Faculty of Medicine, King Salman International University South Sinai, Egypt.
¹⁰ Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna Vienna, Austria.

PMID: 35836886
PMCID: PMC9274568

Abstract

The mechanisms behind prostate adenocarcinoma (PRAD) pathogenicity remain to be understood due to tumor heterogeneity. In the current study, we identified by microarray technology six eligible real hub genes from already identified hub genes through a systematic in silico approach that could be useful to lower the heterogenetic-specific barriers in PRAD patients for diagnosis, prognosis, and treatment. For this purpose, microarray technology-based, already-identified PRAD-associated hub genes were initially explored through extensive literature mining; then, a protein-protein interaction (PPI) network construction of those hub genes and its analysis helped us to identify six most critical genes (real hub genes). Various online available expression databases were then used to explore the tumor driving, diagnostic, and prognostic roles of real hub genes in PRAD patients with different clinicopathologic variables. In total, 124 hub genes were extracted from the literature, and among those genes, six, including CDC20, HMMR, AURKA, CDK1, ASF1B, and CCNB1 were identified as real hub genes by the degree method. Further expression analysis revealed the significant up-regulation of real hub genes in PRAD patients of different races, age groups, and nodal metastasis status relative to controls. Moreover, through correlational analyses, different valuable correlations between treal hub genes expression and different other data (promoter methylation status, genetic alterations, overall survival (OS), tumor purity, CD4+ T, CD8+ T immune cells infiltration, and different other mutant genes and a few more) across PRAD samples were also documented. Ultimately, from this study, a few important transcription factors (TFS), miRNAs, and chemotherapeutic drugs showing a great therapeutic potential were also identified. In conclusion, we have discovered a set of six real hub genes that might be utilized as new biomarkers for lowering heterogenetic-specific barriers in PRAD patients for diagnosis, prognosis, and treatment.

Keywords: PRAD; biomarker; heterogeneity; overall survival (OS); tissue microarray.