Expression of RUNX3 and [beta]-catenin in the carcinogenesis of sporadic colorectal tubular adenoma

• Published in: Tumor biology Vol. 35; no. 6; p. 6039
• Main Authors: Wang, Linna, Li, Dan, Liu, Yang, Wang, Yuan, Cui, Jinfeng, Cui, Airong, Wu, Wenxin
• Format: Journal Article
• Language: English
• Published: London Springer Nature B.V 01.06.2014
• Subjects: Colorectal cancer; Protein expression; Transcription factors; Tumorigenesis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-1800-9

The aim of this study is to investigate the possible roles of runt-related transcription factor 3 (RUNX3) and [beta]-catenin in the carcinogenesis of sporadic colorectal tubular adenomas. The expression of the RUNX3 and [beta]-catenin proteins was evaluated by immunohistochemistry in 23 normal colorectal mucosa (NCM), 81 sporadic colorectal tubular adenomas with different dysplasias (SCTA-D) (mild n=33, moderate n=23, and severe n=25 dysplasia), and 48 sporadic colorectal tubular adenomas with cancerous changes (SCTA-Ca). RUNX3 methylation was assessed by methylation-specific polymerase chain reaction (MSP), combined with laser capture microdissection (LCM), in 17 NCM, 41 SCTA-D (mild n=15, moderate n=12, and severe n=14 dysplasia), and 17 SCTA-Ca tissues. Compared to NCM (82.6 %), RUNX3 in SCTA-D (54.3 %) and SCTA-Ca (27.1 %) was significantly downregulated (P<0.05). In NCM, SCTA-D, and SCTA-Ca, the incidence of positive expression for [beta]-catenin was 13.0, 60.5, and 79.2 %, respectively. A statistically significant difference was observed (P<0.05). RUNX3 levels were markedly higher in adenoma with mild dysplasia (75.8 %) and moderate dysplasia (60.9 %) than in adenoma with severe dysplasia (20.0 %) (both with P<0.05). Likewise, the expression of [beta]-catenin in severe dysplasia adenoma was 84.0 %, which was significantly higher than that in mild dysplasia adenoma (39.4 %). An inverse correlation was found between the protein expression of RUNX3 and [beta]-catenin in SCTA-D and SCTA-Ca (P<0.05). MSP results showed that RUNX3 methylation in NCM, SCTA-D, and SCTA-Ca was 5.9, 17.1, and 41.2 %, respectively, with a statistically significant difference between NCM and SCTA-Ca (P<0.05). However, no significant difference of RUNX3 methylation was observed among different dysplasia groups. RUNX3 and [beta]-catenin play important roles in the carcinogenesis of sporadic colorectal tubular adenomas. In addition, hypermethylation of RUNX3 can downregulate its expression.[PUBLICATION ABSTRACT]