Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates

Li，Xinhui1; Zhou，Jian2; Zhang，Weiwen3; You，Wenhua4,5; Wang，Jun6; Zhou，Linlin7; Liu，Lei8; Chen，Wei Wei9; Li，Hanjie6

2022-11-01

10.3390/cancers14225674

Cancers   影响因子和分区

2072-6694

Tumor cells can be recognized through tumor surface antigens by immune cells and antibodies, which therefore can be used as drug targets for chimeric antigen receptor-T (CAR-T) therapies and antibody drug conjugates (ADCs). In this study, we aimed to identify novel tumor-specific antigens as targets for more effective and safer CAR-T cell therapies and ADCs. Here, we performed differential expression analysis of pan-cancer data obtained from the Cancer Genome Atlas (TCGA), and then performed a series of conditional screenings including Cox regression analysis, Pearson correlation analysis, and risk-score calculation to find tumor-specific cell membrane genes. A tumor tissue-specific and highly expressed gene set containing 3919 genes from 17 cancer types was obtained. Moreover, the prognostic roles of these genes and the functions of these highly expressed membrane proteins were assessed. Notably, 427, 584, 431 and 578 genes were identified as risk factors for LIHC, KIRC, UCEC, and KIRP, respectively. Functional enrichment analysis indicated that these tumor-specific surface proteins might confer tumor cells the ability to invade and metastasize. Furthermore, correlation analysis displayed that most overexpressed membrane proteins were positively correlated to each other. In addition, 371 target membrane protein-coding genes were sifted out by excluding proteins expressed in normal tissues. Apart from the identification of well-validated genes such as GPC3, MSLN and EGFR in the literature, we further confirmed the differential protein expression of 23 proteins: ADD2, DEF6, DOK3, ENO2, FMNL1, MICALL2, PARVG, PSTPIP1, FERMT1, PLEK2, CD109, GNG4, MAPT, OSBPL3, PLXNA1, ROBO1, SLC16A3, SLC26A6, SRGAP2, and TMEM65 in four types of tumors. In summary, our findings reveal novel tumor-specific antigens, which could be potentially used for next-generation CAR-T cell therapies and ADC discovery.

antibody drug conjugates (ADCs) chimeric antigen receptor-T (CAR-T) cell pan-cancer analysis tumor-specific antigens (TSAs)

SCI

英语

其他

National Natural Science Foundation of China[32170919];National Natural Science Foundation of China[92042305];Shenzhen Science and Technology Innovation Program[KQTD20210811090115019];

WOS:000887105100001

2-s2.0-85142499525

Scopus

1.State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou,510275,China
2.Institute of Hepatology,Shenzhen Third People’s Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
3.Department of Gynaecology and Obstetrics,Shenzhen University General Hospital,Shenzhen,518055,China
4.School of Chemistry and Chemical Engineering,Southeast University,Nanjing,211189,China
5.Department of Immunology,Key Laboratory of Human Functional Genomics of Jiangsu Province,Gusu School,Nanjing Medical University,Nanjing,211166,China
6.CAS Key Laboratory of Quantitative Engineering Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China
7.College of Medical Sciences,Qingdao Binhai University,Qingdao,266555,China
8.Shenzhen Key Laboratory of Pathogen and Immunity,National Clinical Research Center for Infectious Disease,State Key Discipline of Infectious Disease,Shenzhen Third People’s Hospital,Second Hospital,Southern University of Science and Technology,Shenzhen,518112,China
9.Department of Clinical Oncology,Li Ka Shing Faculty of Medicine,University of Hong Kong,Pokfulam,Hong Kong

Li，Xinhui,Zhou，Jian,Zhang，Weiwen,et al. Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates[J]. Cancers,2022,14(22).

Li，Xinhui.,Zhou，Jian.,Zhang，Weiwen.,You，Wenhua.,Wang，Jun.,...&Li，Hanjie.(2022).Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates.Cancers,14(22).

Li，Xinhui,et al."Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates".Cancers 14.22(2022).