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肾乳头状细胞癌中用于mRNA疫苗开发的五种肿瘤抗原鉴定及用于个性化医疗的两种免疫亚型鉴定

Identification of Five Tumor Antigens for Development and Two Immune Subtypes for Personalized Medicine of mRNA Vaccines in Papillary Renal Cell Carcinoma.

作者信息

Hu Jianpei, Yuan Zhongze, Jiang Yifen, Mo Zengnan

机构信息

Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China.

Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

出版信息

J Pers Med. 2023 Feb 18;13(2):359. doi: 10.3390/jpm13020359.

Abstract

Increasing evidence has revealed the promise of mRNA-type cancer vaccines as a new direction for cancer immune treatment in several solid tumors, however, its application in papillary renal cell carcinoma (PRCC) remains unclear. The purpose of this study was to identify potential tumor antigens and robust immune subtypes for the development and appropriate use of anti-PRCC mRNA vaccines, respectively. Raw sequencing data and clinical information of PRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The cBioPortal was utilized for the visualization and comparison of genetic alterations. The TIMER was used to assess the correlation between preliminary tumor antigens and the abundance of infiltrated antigen presenting cells (APCs). Immune subtypes were determined by the consensus clustering algorithm, and clinical and molecular discrepancies were further explored for a deeper understanding of immune subtypes. Five tumor antigens, including ALOX15B, HS3ST2, PIGR, ZMYND15 and LIMK1, were identified for PRCC, which were correlated with patients' prognoses and infiltration levels of APCs. Two immune subtypes (IS1 and IS2) were disclosed with obviously distinct clinical and molecular characteristics. Compared with IS2, IS1 exhibited a significantly immune-suppressive phenotype, which largely weakened the efficacy of the mRNA vaccine. Overall, our study provides some insights for the design of anti-PRCC mRNA vaccines and, more importantly, the selection of suitable patients to be vaccinated.

摘要

越来越多的证据表明,信使核糖核酸(mRNA)型癌症疫苗有望成为多种实体瘤癌症免疫治疗的新方向,然而,其在乳头状肾细胞癌(PRCC)中的应用仍不明确。本研究的目的分别是确定潜在的肿瘤抗原和强大的免疫亚型,以开发和合理使用抗PRCC mRNA疫苗。PRCC患者的原始测序数据和临床信息从癌症基因组图谱(TCGA)数据库下载。利用cBioPortal对基因改变进行可视化和比较。使用TIMER评估初步肿瘤抗原与浸润性抗原呈递细胞(APC)丰度之间的相关性。通过一致性聚类算法确定免疫亚型,并进一步探索临床和分子差异,以更深入地了解免疫亚型。确定了PRCC的五种肿瘤抗原,包括ALOX15B、HS3ST2、PIGR、ZMYND15和LIMK1,它们与患者的预后和APC的浸润水平相关。揭示了两种免疫亚型(IS1和IS2),它们具有明显不同的临床和分子特征。与IS2相比,IS1表现出显著的免疫抑制表型,这在很大程度上削弱了mRNA疫苗的疗效。总体而言,我们的研究为抗PRCC mRNA疫苗的设计提供了一些见解,更重要的是,为选择合适的接种患者提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6cc/9965942/a0e8a18d96b5/jpm-13-00359-g001.jpg

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