Simple SummaryGuanine nucleotide-binding protein-like 3 (GNL3) and proliferation-associated protein 2G4 (PA2G4) are molecules involved during metaphase-to-anaphase transition and growth regulation. GNL3 and PA2G4 have been found to be overexpressed in several human cancers, including prostate cancer. Clinical data suggest that GNL3 and PA2G4 could be developed as prognostic biomarkers of clinical significance in prostate cancer. This review article mainly highlights the function of GNL3 and PA2G4 and focuses on the opportunities for their development as prognostic biomarkers in prostate cancer.AbstractProstate cancer is a multifocal and heterogeneous disease common in males and remains the fifth leading cause of cancer-related deaths worldwide. The prognosis of prostate cancer is variable and based on the degree of cancer and its stage at the time of diagnosis. Existing biomarkers for the prognosis of prostate cancer are unreliable and lacks specificity and sensitivity in guiding clinical decision. There is need to search for novel biomarkers having prognostic and predictive capabilities in guiding clinical outcomes. Using a bioinformatics approach, we predicted GNL3 and PA2G4 as biomarkers of prognostic significance in prostate cancer. A progressive increase in the expression of GNL3 and PA2G4 was observed during cancer progression having significant association with poor survival in prostate cancer patients. The Receiver Operating Characteristics of both genes showed improved area under the curve against sensitivity versus specificity in the pooled samples from three different GSE datasets. Overall, our analysis predicted GNL3 and PA2G4 as prognostic biomarkers of clinical significance in prostate cancer.