The role of focal amplifications and extrachromosomal circular DNA (eccDNA) is still uncertain in prostate adenocarcinoma (PRAD). Here, we first mapped the global characterizations of eccDNA and then investigate the characterization of eccDNA-amplified key differentially expressed encoded genes (eKDEGs) in the progression, immune response and immunotherapy of PRAD.
Circular_seq was used in conjunction with the TCGA-PRAD transcriptome dataset to sequence, annotate, and filter for eccDNA-amplified differentially expressed coding genes (eDEGs) in PRAD and para-cancerous normal prostate tissues. Afterwards, risk models were created and eKDEGs linked to the PRAD prognosis were identified using Cox and Lasso regression analysis. The immune microenvironment of the risk model was quantified using a variety of immunological algorithms, which also identified its characteristics with regard to immunotherapy, immune response, and immune infiltration.
In this research, there was no significant difference in the size, type, and chromosomal distribution of eccDNA in PRAD and para-cancerous normal prostate tissues. However, 4,290 differentially expressed eccDNAs were identified and 1,981 coding genes were amplified. Following that, 499 eDEGs were tested in conjunction with the transcriptome dataset from TCGA-PRAD. By using Cox and Lasso regression techniques, ZNF330 and PITPNM3 were identified as eKDEGs of PRAD, and a new PRAD risk model was conducted based on this. Survival analysis showed that the high-risk group of this model was associated with poor prognosis and validated in external data. Immune infiltration analysis showed that the model risks affected immune cell infiltration in PRAD, not only mediating changes in immune cell function, but also correlating with immunophenotyping. Furthermore, the high-risk group was negatively associated with anti-