Clinical Biobank, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
The Key Laboratory of Geriatrics, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
J Cancer Res Clin Oncol. 2023 Feb;149(2):623-637. doi: 10.1007/s00432-022-04285-7. Epub 2022 Oct 14.
To screen efficacious neoantigens for the development of LIHC mRNA vaccines, construct LIHC immune clusters, and therefore select patients who might benefit from vaccination.
RNA-seq data and clinical information of 371 TCGA-LIHC and 231 ICGC-LIHC cohorts were downloaded. Differentially expressed genes and their associations with prognosis were analyzed by GEPIA, genetic alterations were examined in the cBioPortal portal, and the association between genes and immune infiltrating cells was explored by TIMER. The immune clusters were constructed by consistency clustering, and the immune landscape was described using CIBERSORT.
POLR3C and KPNA2 were identified as LIHC tumor neoantigens related to inferior prognosis and antigen-presenting cell infiltration. In addition, three immune clusters (IC1, IC2 and IC3) with significant differences in molecular, immune cytological, and clinical features were identified in both the TCGA and ICGC LIHC cohorts. Immune "hot" phenotype IC3 displayed a better survival than IC2, and immune "cold" phenotype IC1 exhibited a high tumor mutation burden.
In conclusion, for the development of anti-LIHC mRNA vaccines, we identified efficacious neoantigens POLR3C and KPNA2, profiled the tumor microenvironment of LIHC, and identified IC1 patients as the subgroup who might not most benefit from vaccination.
为了筛选有效的肝细胞癌（LIHC）mRNA 疫苗新抗原，构建 LIHC 免疫聚类，从而选择可能受益于疫苗接种的患者。
下载了 371 例 TCGA-LIHC 和 231 例 ICGC-LIHC 队列的 RNA-seq 数据和临床信息。通过 GEPIA 分析差异表达基因及其与预后的关系，在 cBioPortal 门户中检查遗传改变，通过 TIMER 探索基因与免疫浸润细胞的关联。通过一致性聚类构建免疫聚类，并使用 CIBERSORT 描述免疫景观。
POLR3C 和 KPNA2 被鉴定为与预后不良和抗原呈递细胞浸润相关的 LIHC 肿瘤新抗原。此外，在 TCGA 和 ICGC LIHC 队列中均鉴定出三个具有显著分子、免疫细胞学和临床特征差异的免疫聚类（IC1、IC2 和 IC3）。免疫“热”表型 IC3 的生存状况优于 IC2，而免疫“冷”表型 IC1 则表现出较高的肿瘤突变负担。
总之，为了开发抗 LIHC mRNA 疫苗，我们鉴定了有效的新抗原 POLR3C 和 KPNA2，分析了 LIHC 的肿瘤微环境，并确定了 IC1 患者可能不是最受益于疫苗接种的亚组。
