Identification of Neoantigens and Construction of Immune Subtypes in Prostate Adenocarcinoma

Area of Science:

• Oncology
• Immunology
• Vaccinology

Background:

• Messenger ribonucleic acid (mRNA) vaccines represent a promising therapeutic avenue for cancer, yet their effectiveness against prostate adenocarcinoma (PRAD) requires further investigation.
• Understanding the tumor microenvironment and identifying suitable patient populations are crucial for optimizing mRNA vaccine strategies in PRAD.

Purpose of the Study:

• To identify potential tumor antigens for the development of mRNA vaccines targeting prostate adenocarcinoma.
• To characterize immune subtypes within PRAD to identify patient populations who may benefit from mRNA vaccination.

Main Methods:

• Utilized TCGA and ICGC datasets for gene expression and clinical data analysis.
• Employed bioinformatics tools (GEPIA2, cBioPortal, TIMER, ConsensusClusterPlus) for prognostic analysis, genetic alteration assessment, immune cell infiltration correlation, and immune subtype identification.
• Applied graph learning and LASSO logistic analysis for immune landscape depiction and patient stratification for mRNA vaccination.

Main Results:

• Identified seven potential PRAD tumor antigens (ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, UPP1) significantly associated with poor prognosis and antigen-presenting cells.
• Classified PRAD into five distinct immune subtypes based on molecular, cellular, and clinical features, with C1 and C2 exhibiting an immune 'cold' phenotype and C3/C5 an 'hot' but immunosuppressive phenotype.
• Revealed significant immune heterogeneity among PRAD patients.

Conclusions:

• ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, and UPP1 are promising candidates for PRAD mRNA vaccine development.
• PRAD patients classified into immune subtypes C1 and C2 are identified as suitable candidates for mRNA vaccination due to their 'cold' immune phenotype.