Identification and validation of diagnostic and prognostic biomarkers in prostate cancer based on WGCNA

Abstract

Abstract Background Prostate cancer (PCa) represents a significant health challenge for men, and the advancement of the disease often results in a grave prognosis for patients. Therefore, the identification of biomarkers associated with the diagnosis and prognosis of PCa holds paramount importance in patient health management. Methods The datasets pertaining to PCa were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to investigate the modules specifically associated with the diagnosis of PCa. The hub genes were identified using the LASSO regression analysis. The expression levels of these hub genes were further validated by qRT-PCR experiments. Receiver operating characteristic (ROC) curves and nomograms were employed as evaluative measures for assessing the diagnostic value. Results The blue module identified by WGCNA exhibited a strong association with PCa. Six hub genes (SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3) were identified by LASSO regression analysis. Further verification confirmed that these six genes were significantly downregulated in tumor tissues and cells. The six hub genes and the nomogram demonstrated substantial diagnostic value, with area under the curve (AUC) values ranging from 0.754 to 0.961. Moreover, patients with low expression levels of these six genes exhibited elevated T/N pathological stage and Gleason score, implying a more advanced disease state. Meanwhile, their progression-free survival (PFS) was observed to be potentially poorer. Finally, a significant association could be observed between the expression of these genes and the dysregulation of immune cells, along with drug sensitivity. Conclusions In summary, our study identified six hub genes, namely SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3, which can be utilized to establish a diagnostic model for PCa. The discovery may offer potential molecular targets for clinical diagnosis and treatment of PCa.

Keywords

• Prostate cancer
• Diagnosis
• Prognosis
• Biomarker
• WGCNA