Identification of novel biomarker RPS21 using microarray-based whole-gene expression profiling of breast cancer in Saudi women

Breast cancer (BC) is the most common malignancy worldwide, including in Saudi Arabia. Because of its heterogeneous nature, existing diagnostic and prognostic biomarkers are not relevant for all cases. There is a need to discover novel biomarkers for early diagnosis and prognosis to reduce mortality. Herein, we utilized an integrative bioinformatics approach to identify potential biomarkers for BC. Gene expression profiling of 45 BC and five normal samples from KAUH, Jeddah was done with the GeneChip Human Genome 1.0 ST Array. Data was analyzed by LIMMA package of R and differentially expressed genes (DEGs) detected in Saudi Arabian patients were compared with American and Asian datasets. Ingenuity pathway analysis tool and gene ontology enrichment analysis were conducted to find aberrant pathways associated with BC. Survival analysis was done by Kaplan -Meier plotter to establish prognostic importance of identified genes followed by validation using qPCR. The association between RPS21 gene expression and systematic therapeutic response in BC was checked using statistical methods. Our results revealed 870, 658 and 567 DEGs in Saudi Arabian (GSE36295) American (GSE166044) and Asian (GSE15852) patients, respectively. The genes RPS21, CXCL2, TNMD, TOP2A, HMMR, and RRM2 were common in all groups. Pathway analysis revealed cell cycle checkpoints and BC regulation by stathmin1 as the most inhibited and activated pathways, respectively. Gene ontology and protein-protein interaction (PPI) network analysis of DEGs showed the role of ribosome-related genes and pathways in BC. Survival analysis predicted RPS21 to be a potential novel prognostic biomarker. Our findings highlight RPS21 as a good prognostic biomarker candidate for BC in Saudi patients. It could be used globally after validation on bigger cohorts. Functional enrichment and pathway analysis predicted alteration in cell cycle, cancer regulation, and ribosome-related pathways associated with BC and provided critical insights into the molecular mechanisms driving breast tumorigenesis.