Comprehensive profiling of alternative splicing and immune landscapes in rectal cancer: implications for mRNA vaccine...

mRNA vaccines have emerged as a promising platform for cancer immunotherapy, particularly following the success of COVID-19 vaccines. However, the development of cancer vaccines presents challenges such as difficulties in antigen prediction and poor immunogenicity, especially in identifying and delivering highly immunogenic tumor-specific antigens. The variability and low immunogenicity of tumor antigens further complicates this process.

This study utilized public data and bioinformatics analysis to identify potential tumor antigens in cancer and characterize different immune subtypes. This approach aims to guide the development of cancer mRNA vaccines with enhanced immune response.

In the cancer genome atlas rectal adenocarcinoma(TCGA-READ), Exon skipping was the most common alternative splicing event in TCGA-READ, whereas mutually exclusive exons were the least common. We identified 4480 upregulated and 3328 downregulated AS events, with missense mutations being the most frequent. A total of 217 potential antigen genes were identified by intersecting upregulated AS anomalies and frameshift mutations. FAM135A, GAR1, and CDIPT have been highlighted as potential antigens, with FAM135A showing significant correlation with immune cell infiltration. TCGA-READ samples stratified into C1 and C2 subtypes by survival and immune profiles revealed that C2 tumors derive markedly greater benefit from CTLA-4/PD-1 blockade than C1 tumors, underscoring the value of molecular subtyping in guiding precision immunotherapy.

FAM135A was identified as a potential tumor vaccine antigen, and an immune subtype analysis was conducted in different patients. This study provides guidance for the development of novel cancer mRNA vaccines.