Multi-Omics Analysis of the Anoikis Gene CASP8 in Prostate Cancer and Biochemical Recurrence (BCR)

<b>Background:</b> Prostate cancer, as an androgen-dependent malignant tumor in older men, has attracted the attention of a wide range of clinicians. BCR remains a significant challenge following early prostate cancer treatment. <b>Methods:</b> The specific expression pattern of the Anoikis gene set in prostate cancer cells was first explored by single-cell and spatial transcriptomics analysis. Genes causally associated with prostate cancer were screened using Summary-data-based Mendelian Randomization (SMR). Subsequently, we explored the role and mechanism of <i>CASP8</i> in prostate cancer cells and defined a new cell type: the <i>CASP8</i> T cell. We constructed a prediction model that can better predict the BCR of prostate cancer, and explored the differences in various aspects of clinical subgroups, tumor microenvironments, immune checkpoints, drug sensitivities, and tumor-immune circulations between high- and low-risk groups. The results of SMR analysis indicated that <i>CASP8</i> could increase the risk of prostate cancer. Based on the differential genes of <i>CASP8</i>-positive and -negative T cells, we constructed a four-gene prognostic model with a 5-year AUC of 0.713. <b>Results:</b> The results revealed that high-risk prostate cancer BCR patients had various characteristics such as higher tumor purity, higher BCR rate, downregulated SIRPA immune checkpoints, and unique drug sensitivity. <b>Conclusions:</b> In summary, <i>CASP8</i> may be a potential biomarker for prostate cancer.