Disulfidptosis-linked Gene Signatures Constituted of Prognostic Prediction Models in Prostate Cancer

Identification of cancer biomarkers for early detection is required. However, little is known about which candidate cell signaling pathway markers can be identified and which pathways may serve as therapeutic targets. We focused on the disulfidptosis among numerous signaling pathways, because it is a mechanism that causes cell death and is associated with iron-dependent cell death or ferroptosis, the tricarboxylic acid cycle, energy metabolism, and glucose uptake. The aim of the study was to detect the disulfidptosis-linked gene signatures associated with stage-specific makers and prognosis.

We examined the expression of 106 related genes in 324 patients with prostate cancer for disulfidptosis, a type of cell death triggered by disulfide stress resulting in disulfide bond-induced collapse of the cytoskeleton.

The expression levels of UBASH3B, ANP32E, PRC1, ACTB, SPG20, and DBN1 increased with cancer progression. Of these, UBASH3B, PRC1, and ANP32E were strongly expressed in cases with Gleason score ≥8. Conversely, the expression levels of MYH13, FLNC, GLUD1, SAMM50, CHCHD3, and CAPZB decreased. Of these, GLUD1, CAPZB, and SAMM50 were decreased in cases with Gleason score ≥8. In addition, UBASH3B, ANP32E, PRC1, DBN1, FLNC, and GLUD1 enabled the estimation of biochemical recurrence (BCR)-free survival. In particular, the prognostic formula comprising ZHX2, SMPD4, and CHD4 using the Lasso-Cox regression model properly distinguished the BCR-free survival curves, indicating that these genes could be signatures for disulfidptosis.

Decoding disulfidptosis-related data in the transcriptome would provide crucial clues for finding novel approaches to personalized cancer medicine in prostate cancer.