title: Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis.
abstract: Advanced technology in molecular biology has provided us powerful tools for the diagnosis and treatment for cancer. We herein adopted a new methodology to identify a novel cancer/testis (CT) antigen with high frequency of expression in colorectal cancer as follows: (a) combining laser microdissection and cDNA microarray was used to analyze the gene expression profile of colorectal cancer cells; (b) genes overexpressed in testis and underexpressed in normal colon epithelium were analyzed using cDNA microarray; and (c) the gene expression profile of colorectal cancer cells was compared with that of normal testis. Using this methodology, we selected 38 candidates for CT antigen. Among these genes, we identified a novel CT antigen, serine/threonine kinase 31 (STK31), which was previously reported as a gene expressed in spermatogonia. Reverse transcription-PCR analysis showed that STK31 gene expression levels in cancer samples were significantly higher (P < 0.0001) than those in normal samples. The STK31 gene was frequently expressed not only in colorectal cancer but also in gastric and esophageal cancer. Moreover, STK31 peptide was able to elicit specific CTLs and induced CTLs lysed either peptide-loading or endogenously STK31-expressing target cells. These results showed that the new methodology in this study facilitated identification of CT antigens and that STK31 may be a candidate for cancer immunotherapy against gastrointestinal cancer.
authors.affiliation: Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoe
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ohmachi
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013737:Testis / Q000201:enzymology / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases