title: An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer.
abstract: Insulin gene enhancer binding protein-1 (ISL-1) is a transcription factor involved in development of the heart, motor neurons, and pancreas. Our previous study indicated that ISL-1 was overexpressed in gastric cancer but not in other gastrointestinal tumors. However, no immunohistochemical or clinicopathological studies of ISL-1 in gastric carcinoma have been performed. The aim of this study was to determine the expression and prognostic value of ISL-1 in gastric carcinoma. A nude mouse xenograft model was established to study the role of ISL-1 on cancer genesis and development in vivo. Overexpression of ISL-1 significantly enhanced the tumorigenicity of NIH3T3 cells in vivo. ISL-1 expression was evaluated using immunohistochemistry in 456 human gastric carcinoma and normal tissues. ISL-1 was significantly overexpressed in gastric adenocarcinoma compared with normal gastric tissues. ISL-1 expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage, and histological grade (P < .05, χ(2) test). Positive ISL-1 expression was associated with poorer 5-year overall survival in gastric cancer (P = .001, log-rank test). Multivariate Cox regression analysis demonstrated that ISL-1 expression (P = .047) could be an independent prognostic factor for overall survival in gastric carcinoma. This study suggests that ISL-1 may be a useful prognostic biomarker and may represent a novel therapeutic target for gastric adenocarcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Key Laboratory of Protein Posttranslational Modifications and Cell Function (Beijing), Peking University,38 Xue Yuan Rd, Beijing 100191, China. Electronic address: guochen0606@bjmu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Key Laboratory of Protein Posttranslational Modifications and Cell Function (Beijing), Peking University,38 Xue Yuan Rd, Beijing 100191, China. Electronic address: wwp@bjmu.edu.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Key Laboratory of Protein Posttranslational Modifications and Cell Function (Beijing), Peking University,38 Xue Yuan Rd, Beijing 100191, China. Electronic address: stonejane@126.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Key Laboratory of Protein Posttranslational Modifications and Cell Function (Beijing), Peking University,38 Xue Yuan Rd, Beijing 100191, China. Electronic address: chenpinglk@bjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Key Laboratory of Protein Posttranslational Modifications and Cell Function (Beijing), Peking University,38 Xue Yuan Rd, Beijing 100191, China. Electronic address: chunyanzhou@bjmu.edu.cn.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D041681:NIH 3T3 Cells; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1
keywords: Gastric cancer; ISL-1; Immunohistochemistry; Overall survival; Prognostic biomarker