Screening of tumor antigens and immunogenic cell death landscapes of prostate cancer for exploration of mRNA vaccine

Abstract

Abstract Background Although the mRNA vaccine is effective against many kinds of cancers, its efficacy against prostate adenocarcinoma (PRAD) is still unclear. In this study, effective antigens of mRNA vaccine were excavated from the perspective of immunogenic cell death (ICD), and ICD subtypes of PRAD were further distinguished to establish an ICD landscape, thereby determining suitable vaccine recipients. Methods The Cancer Genome Atlas (TCGA) and Memorial Sloan-Kettering Cancer Center (MSKCC) databases were applied to acquire RNA-seq data and corresponding clinical data of 554 and 131 patients, respectively. GEPIA was employed to measure prognostic indices. Then comparison of genetic alterations was performed utilizing cBioPortal, and correlation of identified ICD antigens with immune infiltrating cells was analyzed employing TIMER. Moreover, ICD subtypes were identified by means of consensus cluster, and ICD landscape of PRAD was depicted utilizing graph learning-based dimensional reduction. Results In total, 4 PRAD antigens were identified in PRAD, including FUS, LMNB2, RNPC3 and ZNF700, which had association with adverse prognosis and infiltration of antigen-presenting cells (APCs). PRAD patients were classified as two ICD subtypes based on their differences in molecular, cellular and clinical features. Patients in subtype ICDS2 had immune “hot” phenotype, whereas those in ICDS1 had an immune “cold” phenotype. Furthermore, ICD modulators and immune checkpoints were also differentially expressed between two ICD subtype tumors. Finally, ICD landscape of PRAD showed substantial heterogeneity among individual patients. Conclusions FUS, LMNB2, RNPC3 and ZNF700 are identified as antigens with potential to develop anti-PRAD mRNA vaccine, particularly for patients in subtype ICDS2. In summary, the research may provide a theoretical foundation for developing mRNA vaccine against PRAD as well as determining appropriate vaccine recipients.