AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Genes & Diseases Article
PDF (4 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Integrated bioinformatics identifies the dysregulation induced by aberrant gene methylation in colorectal carcinoma

Zhenyu Ye,1, Yecheng Li,1, Jiaming Xie, Zhenyu Feng, Xiaodong Yang, Yong Wu, Yuwei Pu, Jiawei Gao, Xiangrong Xu, Zhaobi Zhu, Wei Li, Wei Chen( ), Chungen Xing( )
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215004, PR China

1 Contributed equally to the manuscript.]]>

Show Author Information

Abstract

Colorectal carcinoma (CRC) is one of the most common cancers, and is associated with a poor clinical outcome. The key genes and potential prognostic markers in colorectal carcinoma remain to be identified and explored for clinical application. DNA expression/methylation profiles were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed/methylated genes (DEGs and DEMs). A total of 255 genes and 372 genes were identified as being up-regulated and down-regulated, respectively, in GSE113513, GSE81558, and GSE89076. There were a total of 3350 hypermethylated genes and 443 hypomethylated genes identified in GSE48684. Twenty genes were found to be hypermethylated as well as down-regulated, and a functional enrichment analysis revealed that these genes were mainly involved in cancer-related pathways. Among these 20 genes, GPM6A, HAND2 and C2orf40 were related to poor outcomes in cancer patients based on a survival analysis. Concurrent decreases of GPM6A, HAND2 and C2orf40 protein expression were observed in highly-differentiated colorectal carcinoma tissues, and higher expression levels were found in undifferentiated or minimally-differentiated colorectal carcinoma tissues. In conclusion, 20 genes were found to be downregulated and hypermethylated in CRC, among which GPM6A, HAND2 and C2orf40 were explored for their potential prognostic value.

Keywords

BioinformaticsColorectal carcinomaC2orf40GPM6AHAND2Hypermethylation

References

1

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30.
Crossref Google Scholar
2

Marmol I, Sanchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. 2017;18(1),e197.
Crossref Google Scholar
3

Chi Y, Zhou D. MicroRNAs in colorectal carcinoma--from pathogenesis to therapy. J Exp Clin Canc Res : CR (Clim Res). 2016;35,e43.
Crossref Google Scholar
4

Van Cutsem E, Cervantes A, Nordlinger B, Arnold D. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol: Off J Eur Soc Med Oncol. 2014;25(Suppl 3):ⅲ1-ⅲ9.
Crossref Google Scholar
5

Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol : Off J Eur Soc Med Oncol. 2016;27(8):1386-1422.
Crossref Google Scholar
6

Gotze S, Feldhaus V, Traska T, et al. ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma. BMC Canc. 2009;9,e447.
Crossref Google Scholar
7

Liu J, Li H, Sun L, et al. Epigenetic alternations of MicroRNAs and DNA methylation contribute to liver metastasis of colorectal cancer. Dig Dis Sci. 2019;64(6):1523-1534.
Crossref Google Scholar
8

Luo Y, Wong CJ, Kaz AM, et al. Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology. 2014;147(2):418-429.E7706.
Crossref Google Scholar
9

Satoh K, Yachida S, Sugimoto M, et al. Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC. Proc Natl Acad Sci USA. 2017;114(37):E7697.
Crossref Google Scholar
10

Sayagues JM, Corchete LA, Gutierrez ML, et al. Genomic characterization of liver metastases from colorectal cancer patients. Oncotarget. 2016;7:72908-72922.
Crossref Google Scholar
11

Gautier L, Cope L, Bolstad BM, Irizarry RA. affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307-315.
Crossref Google Scholar
12

Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.
Crossref Google Scholar
13

Pidsley R, Wong CC, Volta M, et al. A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genom. 2013;14,e293.
Crossref Google Scholar
14

Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-D613.
Crossref Google Scholar
15

Brocardo M, Henderson BR. APC shuttling to the membrane, nucleus and beyond. Trends Cell Biol. 2008;18(12):587-596.
Crossref Google Scholar
16

Fearon ER. Molecular genetics of colorectal cancer. Ann RevPathol. 2011;6:479-507.
Crossref Google Scholar
17

Javelaud D, Mauviel A. Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-beta: implications for carcinogenesis. Oncogene. 2005;24(37):5742-5750.
Crossref Google Scholar
18

Wang C, Li P, Xuan J, et al. Cholesterol enhances colorectal cancer progression via ROS elevation and MAPK signaling pathway activation. Cell Physiol Biochem. 2017;42(2):729-742.
Crossref Google Scholar
19

Sun B, Hu X, Liu G, et al. Phosphatase Wip1 negatively regulates neutrophil migration and inflammation. J Immunol. 2014;192(3):1184-1195.
Crossref Google Scholar
20

Michibata H, Okuno T, Konishi N, et al. Human GPM6A is associated with differentiation and neuronal migration of neurons derived from human embryonic stem cells. Stem Cell Dev. 2009;18(4):629-639.
Crossref Google Scholar
21

Charfi C, Edouard E, Rassart E. Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol. 2014;37(3):179-191.
Crossref Google Scholar
22

Firulli AB. A HANDful of questions: the molecular biology of the heart and neural crest derivatives (HAND)-subclass of basic helix-loop-helix transcription factors. Gene. 2003;312:27-40.
Crossref Google Scholar
23

Hua Y, Ma X, Liu X, et al. Abnormal expression of mRNA, microRNA alteration and aberrant DNA methylation patterns in rectal adenocarcinoma. PloS One. 2017;12,e0174461.
Crossref Google Scholar
24

Pradhan MP, Desai A, Palakal MJ. Systems biology approach to stage-wise characterization of epigenetic genes in lung adenocarcinoma. BMC Syst Biol. 2013;7,e141.
Crossref Google Scholar
25

Yang Y, Chu FH, Xu WR, et al. Identification of regulatory role of DNA methylation in colon cancer gene expression via systematic bioinformatics analysis. Medicine. 2017;96,e8487.
Crossref Google Scholar
26

Jones A, Teschendorff AE, Li Q, et al. Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development. PLoS Med. 2013;10,e1001551.
Crossref Google Scholar
27

Yue CM, Deng DJ, Bi MX, Guo LP, Lu SH. Expression of ECRG4, a novel esophageal cancer-related gene, downregulated by CpG island hypermethylation in human esophageal squamous cell carcinoma. World J Gastroenterol. 2003;9(6):1174-1178.
Crossref Google Scholar
28

Lu J, Wen M, Huang Y, et al. C2ORF40 suppresses breast cancer cell proliferation and invasion through modulating expression of M phase cell cycle genes. Epigenetics. 2013;8(6):571-583.
Crossref Google Scholar
Genes & Diseases
Volume 8 Issue 4,
July 2021
Pages 521-530
DOI: 10.1016/j.gendis.2020.04.008
Cite this article:
Ye Z, Li Y, Xie J, et al. Integrated bioinformatics identifies the dysregulation induced by aberrant gene methylation in colorectal carcinoma. Genes & Diseases, 2021, 8(4): 521-530. https://doi.org/10.1016/j.gendis.2020.04.008

264

Views

2

Downloads

6

Crossref

N/A

Web of Science

6

Scopus

0

CSCD

Altmetrics
Received: 18 January 2020
Revised: 31 March 2020
Accepted: 09 April 2020
Published: 24 May 2020
© 2020, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return