Implications of the KHDC4-TRAF2 axis in the context of prostate cancer prognosis

Abstract

The inability to effectively identify the formation of advanced-stage tumors poses a challenge in precisely determining when to intervene in prostate cancer (PCa). Despite the use of PSA as a screening factor, it still falls short in significantly improving the diagnosis and prognosis of advanced PCa. Identifying novel prognosis biomarkers to assist in confirming the progression of advanced PCa will contribute to more precise and effective therapeutic approaches. Through a comparative analysis between late-stage and early-stage TCGA-PRAD transcriptomes, KHDC4 has been identified as a key and specific member of the KHDC family that shows increased expression in PCa. The elevated levels of KHDC4 in late-stage and lymph node metastasis are positively correlated with poorer overall survival and disease-free survival rates in PCa patients. Simulated molecular regulation networks and in vitro results support the notion that the KHDC4-TRAF2 axis contributes to tumor malignancy features in late-stage and lymph node metastasis tumor samples, consequently correlating with worse progression-free interval and disease-free interval prognosis values in TCGA-PRAD. It is noteworthy that the positive correlation of the distribution of KHDC4 and TRAF2 with the Gleason score is superior to that of KLK3. Promoter analysis reveals that KHDC4 and TRAF2 share a similar upstream regulator, E2F4, for their transactivation. Molecular simulated profiles, mimicking downstream effectors under both KHDC4 and TRAF2 regulation, can be utilized as signatures for overall survival and disease-free survival prognosis purposes. In conclusion, this systematic analysis study indicates that the axis of KHDC4-TRAF2 may serve as a valuable prognostic model for evaluating advanced PCa.