title: Immune response-associated gene analysis of 1,000 cancer patients using whole-exome sequencing and gene expression profiling-Project HOPE.
abstract: Project HOPE (High-tech Omics-based Patient Evaluation) has been progressing since its implementation in 2014 using whole-exome sequencing (WES) and gene expression profiling (GEP). With the aim of evaluating immune status in cancer patients, a gene panel consisting of 164 immune response-associated genes (56 antigen-presenting cell and T-cell-associated genes, 34 cytokine- and metabolism-associated genes, 47 TNF and TNF receptor superfamily genes, and 27 regulatory T-cell-associated genes) was established, and its expression and mutation status were investigated using 1,000 cancer patient-derived tumors. Regarding WES, sequencing and variant calling were performed using the Ion Proton system. The average number of single-nucleotide variants (SNVs) detected per sample was 183 ± 507, and the number of hypermutators with more than 500 total SNVs was 51 cases. Regarding GEP, seven immune response-associated genes (VTCN1, IL2RA, ULBP2, TREM1, MSR1, TNFSF9 and TNFRSF12A) were more than 2-fold overexpressed compared with normal tissues in more than 2 organs. Specifically, the positive rate of PD-L1 expression in all patients was 25.8%, and PD-L1 expression was significantly upregulated in hypermutators. The simultaneous analyses of WES and GEP based on immune response-associated genes are very intriguing tools to screen cancer patients suitable for immune checkpoint antibody therapy.
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Ryota
authors.initials: R
authors.lastname: Kondou
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Tomoe
authors.initials: T
authors.lastname: Tanabe
authors.forename: Sumiko
authors.initials: S
authors.lastname: Ohnami
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ohnami
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.forename: Tohru
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology; D004843:Epistasis, Genetic; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007109:Immunity / Q000235:genetics*; D056747:Immunomodulation / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D011379:Prognosis
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human