Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and...

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Main Authors: Miaowei Wu, Weiyang Lou, Meng Lou, Peifen Fu, Xiao-Fang Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2020.576615/full
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spelling doaj-0beb2417ace94770ba246aa566ae63e22020-11-25T03:36:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.576615576615Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon AdenocarcinomaMiaowei Wu0Weiyang Lou1Meng Lou2Peifen Fu3Xiao-Fang Yu4Cancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Breast Surgery, First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, ChinaCancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Breast Surgery, First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, ChinaCancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaBackground: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients.Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated.Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD.Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.https://www.frontiersin.org/articles/10.3389/fonc.2020.576615/fullcolon adenocarcinomametastasissurvivaldrugbioinformatics analysis
collection DOAJ
language English
format Article
sources DOAJ
author Miaowei Wu
Weiyang Lou
Meng Lou
Peifen Fu
Xiao-Fang Yu
spellingShingle Miaowei Wu
Weiyang Lou
Meng Lou
Peifen Fu
Xiao-Fang Yu
Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
Frontiers in Oncology
colon adenocarcinoma
metastasis
survival
drug
bioinformatics analysis
author_facet Miaowei Wu
Weiyang Lou
Meng Lou
Peifen Fu
Xiao-Fang Yu
author_sort Miaowei Wu
title Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
title_short Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
title_full Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
title_fullStr Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
title_full_unstemmed Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma
title_sort integrated analysis of distant metastasis-associated genes and potential drugs in colon adenocarcinoma
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2020-10-01
description Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients.Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated.Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD.Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.
topic colon adenocarcinoma
metastasis
survival
drug
bioinformatics analysis
url https://www.frontiersin.org/articles/10.3389/fonc.2020.576615/full
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