PARP8 (Poly(ADP-Ribose) Polymerase Family Member 8)

The prognostic model based on 8 immune-related genes effectively predicted the survival outcomes of UM. Knockdown of CEBPB significantly reduced the progression of UM, suggesting that it could be a potential therapeutic target for UM.

The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa.

In conclusion, we developed a robust and powerful ICD-related signature for evaluating the prognosis and benefits of immunotherapy that could serve as a promising tool to guide decision-making and surveillance for UVM patients.

In silico functional annotation of these loci suggested lead variant-target genes that could be assigned to the discrete pathways of mitotic spindle assembly (INCENP, CENPN, ZWILCH, MAD1L1), p53 signaling (TP53, MDM4, SPI1), DNA damage repair (ATM, RAD51C, CHEK2, USP28, PARP8), and myeloid oncogenesis (WT1, HOXA9, L3MBTL3). Our novel approach combining the latest and largest blood somatic genomic trait GWAS with large-scale solid tumor risk GWAS thus yielded clear mechanistic insights into the shared inherited genetic basis of solid tumor risk and somatic genomic traits.