Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2017; 23(17): 3066-3076
Published online May 7, 2017. doi: 10.3748/wjg.v23.i17.3066
Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression
Tian-Wen Yang, Yun-Han Gao, Sha-Ying Ma, Qiang Wu, Zhong-Fu Li
Tian-Wen Yang, Department of Gastroenterology, Yongchuan Hospital, Chongqing Medical University, Chongqing 400014, China
Yun-Han Gao, Sha-Ying Ma, Qiang Wu, Zhong-Fu Li, Department of General Surgery, Chongqing Emergency Medical Center, Chongqing 400014, China
Author contributions: Yang TW and Gao YH contributed equally to this work and should be as the co-first authors; Yang TW, Gao YH, Ma SY, Wu Q and Li ZF designed the research; Gao YH and Ma SY performed the research; Wu Q analyzed the data; Yang TW wrote the paper.
Supported by the Yongchuan Chongqing Medical University Hospital Fund, No. YJYB2012009.
Institutional review board statement: This study was approved by the Ethics Committee of Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Informed consent statement: All subjects recruited for this study provided written informed consent prior to participation.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zhong-Fu Li, MD, Department of General Surgery, Chongqing Emergency Medical Center, No. 1, Jiankang Road, Yongchuan District, Chongqing 400014, China. li_zhongfu@sina.com
Telephone: +86-23-63692253 Fax: +86-23-63692253
Received: September 11, 2016
Peer-review started: September 12, 2016
First decision: October 20, 2016
Revised: December 7, 2016
Accepted: January 18, 2017
Article in press: January 18, 2017
Published online: May 7, 2017
Processing time: 236 Days and 22.8 Hours
Abstract
AIM

To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.

METHODS

Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (APC, BRAF, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. Western blots, luciferase assays for β-catenin-T-cell factor protein/β-catenin-lymphoid enhancer factor (β-catenin-TCF/LEF)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines.

RESULTS

Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency (both P < 0.05). Slightly elevated lesions showed a significantly lower AI (P < 0.05). β-catenin and β-catenin-TCF/LEF-driven transcriptional activity was significantly upregulated in slightly elevated lesions (both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated (both P < 0.05). β-catenin-TCF/LEF-driven transcriptional activity was negatively correlated with c-Myc (ρ = -0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-xL upregulation (both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity (both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-xL (ρ = -0.74 and -0.78, respectively).

CONCLUSION

The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.

Keywords: Cancer; Carcinoma; Colorectal; Adenoma; β-catenin; Non-polypoid

Core tip: We comparatively investigated the cellular and molecular characteristics of low-grade slightly elevated adenomas and low-grade polypoid adenomas. Slightly elevated lesions displayed a significantly lower apoptotic index as well as significantly upregulated β-catenin expression and β-catenin-TCF/LEF-driven transcriptional activity. Slightly elevated lesions also displayed c-Myc downregulation, cyclin D1 upregulation, upregulation of Bcl-2 and Bcl-xL, and downregulation of caspase-9 and caspase-3 activity. Low-grade slightly elevated adenomas displayed a lower apoptotic activity relative to low-grade polypoid adenomas, which can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.