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开发 mRNA 疫苗用于肝癌的肿瘤抗原的发现和鉴定。

Discovery and characterization of tumor antigens in hepatocellular carcinoma for mRNA vaccine development.

机构信息

Department of Translational Medicine Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China.

Institute of Hepatology and Metabolic Diseases, Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China.

出版信息

J Cancer Res Clin Oncol. 2023 Jul;149(7):4047-4061. doi: 10.1007/s00432-022-04325-2. Epub 2022 Aug 29.

DOI:10.1007/s00432-022-04325-2
PMID:36038676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9423891/
Abstract

BACKGROUND

mRNA vaccines are emerging as new targets for cancer immunotherapy. However, the potential tumor antigens for mRNA vaccine design in hepatocellular carcinoma (HCC) remain to be elucidated.

METHODS

Genetic and RNA-Seq data were obtained from TCGA and ICGC. Tumor-specific antigens (TSAs) were identified by differential expression, mutation status, HLA binding, antigen-presenting cell (APC) correlation, immune checkpoint (ICP) relevance and prognosis. Consensus clustering was used for patient classification. The molecular and immune status of TSAs and clustered patients, including prognostic ability, tumor microenvironment, tumor-related signature and tumor immune dysfunction and exclusion (TIDE), were further characterized.

RESULTS

Five dysregulated and mutated TSAs were identified in HCC (TSA5): FXYD6, JAM2, GALNT16, C7, and CCDC146. Seven immune gene modules and five immune subtypes (IS1-IS5) of HCC were identified. The immune subtypes and TSA5-related modules showed distinct molecular, cellular and clinical characteristics. According to our study, IS1 patients may be suitable for vaccination.

摘要

背景

mRNA 疫苗作为癌症免疫疗法的新靶点正在出现。然而，肝细胞癌 (HCC) mRNA 疫苗设计的潜在肿瘤抗原仍有待阐明。

方法

从 TCGA 和 ICGC 获得遗传和 RNA-Seq 数据。通过差异表达、突变状态、HLA 结合、抗原呈递细胞 (APC) 相关性、免疫检查点 (ICP) 相关性和预后来识别肿瘤特异性抗原 (TSA)。采用共识聚类对患者进行分类。进一步对 TSA 和聚类患者的分子和免疫状态进行了特征描述，包括预后能力、肿瘤微环境、肿瘤相关特征和肿瘤免疫功能障碍和排斥 (TIDE)。

结果

在 HCC 中鉴定出 5 个失调和突变的 TSA（TSA5）：FXYD6、JAM2、GALNT16、C7 和 CCDC146。鉴定出 7 个 HCC 的免疫基因模块和 5 个免疫亚型（IS1-IS5）。免疫亚型和 TSA5 相关模块表现出不同的分子、细胞和临床特征。根据我们的研究，IS1 患者可能适合接种疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/970ace5e8f07/432_2022_4325_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/1d841f65662a/432_2022_4325_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/a198661851d7/432_2022_4325_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/519f7612eff3/432_2022_4325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/f0a71380570d/432_2022_4325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/5906e06b05f5/432_2022_4325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/10a52aa85494/432_2022_4325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/b35554a19a17/432_2022_4325_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/91d22c40ff3e/432_2022_4325_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/970ace5e8f07/432_2022_4325_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/1d841f65662a/432_2022_4325_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/a198661851d7/432_2022_4325_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/519f7612eff3/432_2022_4325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/f0a71380570d/432_2022_4325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/5906e06b05f5/432_2022_4325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/10a52aa85494/432_2022_4325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/b35554a19a17/432_2022_4325_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/91d22c40ff3e/432_2022_4325_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/11796662/970ace5e8f07/432_2022_4325_Fig9_HTML.jpg

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