Clinical and Translational Research
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2020; 8(15): 3197-3208
Published online Aug 6, 2020. doi: 10.12998/wjcc.v8.i15.3197
Overexpression of AMPD2 indicates poor prognosis in colorectal cancer patients via the Notch3 signaling pathway
Qi-Zhong Gao, Yan Qin, Wei-Jia Wang, Bo-Jian Fei, Wei-Feng Han, Jian-Qiang Jin, Xiang Gao
Qi-Zhong Gao, Bo-Jian Fei, Wei-Feng Han, Department of Gastrocolorectal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214100, Jiangsu Province, China
Yan Qin, Wei-Jia Wang, Jian-Qiang Jin, Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi 214000, Jiangsu Province, China
Xiang Gao, Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu Province, China
Author contributions: Gao QZ and Qin Y designed the research; Gao QZ performed the research. Qin Y and Jin JQ reviewed the surgical pathology; Fei BJ and Han WF analyzed the data; Gao QZ and Gao X wrote the paper; all authors read and approved the final manuscript.
Supported by the Wuxi Young Medical Talents, Jiangsu Province, China, No. QNRC063.
Institutional review board statement: This study was approved by the Ethics Committee of Affiliated Hospital of Jiangnan University and was performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments.
Clinical trial registration statement: This registration policy applies to prospective, randomized, controlled trials only.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Xiang Gao, MD, Academic Research, Department of Oncology, Affiliated Hospital of Jiangnan University, No. 200 Huihe Road, Wuxi 214062, Jiangsu Province, China. 13606189128@139.com
Received: March 24, 2020
Peer-review started: March 24, 2020
First decision: April 24, 2020
Revised: May 26, 2020
Accepted: July 15, 2020
Article in press: July 15, 2020
Published online: August 6, 2020
Abstract
BACKGROUND

AMPD2 is a critical enzyme catalyzing smooth muscle energy supply and metabolism; however, its cellular biological function and clinical implication in colorectal cancer (CRC) are largely unknown.

AIM

To clarify the role of AMPD2 in CRC and study the pathway and prognostic value of its role.

METHODS

AMPD2 expression was analyzed by integrated bioinformatics analysis based on TCGA data sets and immunohistochemistry in tissue microarrays, and the correlation between AMPD2 expression and clinicopathological parameters, Notch3 expression, and prognostic features was assessed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then performed to investigate the regulatory pathway involved. The effects of AMPD2 expression on CRC cells and Notch3 protein expression were investigated by downregulation and overexpression of AMPD2.

RESULTS

AMPD2 mRNA was significantly overexpressed in tumor tissue when compared with normal tissue in a cohort of the TCGA-COAD data set. Biological function enrichment analysis indicated that the Notch pathway strongly correlated with AMPD2 expression, and that the expression of Notch3 and JAG2 mRNA was positively associated with AMPD2 in CRC tissues. In vitro, AMPD2 overexpression markedly reduced Notch3 protein expression in CRC cells, while knockdown of AMPD2 showed the opposite findings. In addition, protein expression was significantly up-regulated in our CRC cohort as indicated by tissue microarray analysis. High expression of AMPD2 protein correlated with advanced depth of tumor and poor differentiation. Furthermore, high AMPD2 expression in CRC tissues was an indicator of poor outcome for CRC patients.

CONCLUSION

AMPD2 is commonly overexpressed in CRC, and acts as a metabolism oncogene to induce CRC progression through the Notch signaling pathway. Thus, AMPD2 may be a novel prognostic biomarker for CRC.

Keywords: Colorectal cancer, AMPD2, Notch3, Tumor metabolism, Poor prognosis, Biomarkers

Core tip: In this study, we summarized and analyzed the mRNA expression data of TCGA-COAD and obtained the expression features of AMPD2 in cancer tissues and adjacent tissues in patients with colorectal cancer. We constructed cell samples that were not subjected to high-throughput sequencing of RNA-seq, and although the results were closer to clinical reality, in the case of verification experiments, the probability of false negatives was increased. In addition, our cytology validation experiments need to be carried out in more detail, and our colorectal cancer cohort sample was only 201 cases. We expect to add cytological evidence and a large sample of prospective prognostic cohorts in subsequent studies.