Identifying Potential Tumor Antigens and Antigens-Related Subtypes in Hepatocellular Carcinoma for mRNA Vaccine Development.

Identifying Potential Tumor Antigens and Antigens-Related Subtypes in Hepatocellular Carcinoma for mRNA Vaccine Development.
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鉴定肝细胞癌中潜在的肿瘤抗原和抗原相关亚型,用于 mRNA 疫苗的开发

DOI:
10.1155/2022/6851026
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发表时间:
2022
影响因子:
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通讯作者:
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中科院分区:
医学3区
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mRNA疫苗已成为癌症治疗的一个有前途的平台。许多研究一直致力于发现新的有效的癌症相关抗原,以开发针对癌症的mRNA疫苗。此外,免疫分型反映了机体的免疫状态,免疫分型的免疫微环境与治疗反应有关。然而,用于mRNA疫苗和肝细胞癌(LIHC)免疫分型的潜在抗原仍远未被理解。 在这项研究中,我们收集了ICGC和TCGA数据库中的基因表达数据和临床信息数据。使用GEPIA 2,我们计算差异表达基因和预后指数。应用TIMER软件计算免疫浸润细胞与各基因的相关系数。使用共有簇对LIHC进行免疫分型。 我们在两个独立的数据集中发现了四个最有潜力的候选者,包括PES 1,MCM 3,PPM 1G和KPNA 2,它们都与LIHC中的抗原呈递细胞(APC)浸润和生存不良相关。此外,还鉴定了LIHC的三种免疫相关亚型(IS 1-IS 3)。所有这些结果都在两个独立的数据集中得到验证。此外,我们在体外验证了我们的结果。 上述候选基因有望成为开发抗LIHC mRNA疫苗的潜在抗原基因,此外,IS 2和IS 3肿瘤患者被认为适合于LIHC的mRNA疫苗。
The mRNA vaccine has become a promising platform for cancer therapy. Lots of studies have been focusing on discovering novel potent cancer-associated antigens to develop mRNA vaccines against cancers. Besides, immunotyping shows the immune status, and immune microenvironment of immunotyping is related with therapeutic reaction. However, potential antigens for mRNA vaccines and immunotyping of liver hepatocellular carcinoma (LIHC) remain far from being understood. In this study, we collected gene expression data and clinical information data from ICGC and TCGA databases. Using GEPIA2, we calculated differential expression genes and prognostic indices. We applied TIMER to calculate the correlation coefficient between immune infiltrating cells and each gene. Consensus cluster was used for immunotyping of LIHC. We uncovered four most potential candidates including PES1, MCM3, PPM1G, and KPNA2, which were all related with antigen-presenting cell (APC) infiltration and poor survival in LIHC in two independent datasets. Furthermore, three immune-related subtypes (IS1-IS3) of LIHC were identified. All these results were validated in two independent datasets. Furthermore, we validated our results in vitro. The above candidates will be expected to be potential antigen genes for developing anti-LIHC mRNA vaccine, and furthermore, patients with IS2 and IS3 tumors are supposed to be appropriate for mRNA vaccine in LIHC.
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