Distinguishing colorectal adenoma from hyperplastic polyp by WNT2 expression.
Aged
Colonic Polyps
/ diagnosis
Colorectal Neoplasms
/ diagnosis
Computational Biology
Diagnosis, Differential
Extracellular Matrix
/ metabolism
Female
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Male
Middle Aged
Protein Interaction Maps
/ genetics
Transcriptome
/ genetics
Wnt Signaling Pathway
/ genetics
Wnt2 Protein
/ genetics
WNT2
Wnt signaling pathway
bioinformatics
colorectal adenoma
extracellular matrix
hyperplastic polyp
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
revised:
21
07
2021
received:
02
06
2021
accepted:
30
07
2021
pubmed:
4
9
2021
medline:
1
2
2022
entrez:
3
9
2021
Statut:
ppublish
Résumé
Colorectal adenoma (CRA) is a classical premalignant lesion, with high incidence and mainly coexisting with hyperplastic polyp (HPP). Hence, this study aimed to distinguish CRA from HPP by molecular expression profiling and advance the prevention of CRA and its malignance. CRA and paired HPP biopsies were collected by endoscopy. Through RNA-sequencing (RNA-seq), the differentially expressed genes (DEGs) were obtained. Functional enrichment analysis was performed based on the DEGs. The STRING database and Cytoscape were used to construct the protein-protein interaction (PPI) network and perform module analysis. Hub genes were validated by real-time quantitative PCR (RT-qPCR) and immunohistochemistry. The ROC curve was drawn to establish the specificity of the hub genes. 485 significant DEGs were identified including 133 up-regulated and 352 down-regulated. The top 10 up-regulated genes were DLX5, MMP10, TAC1, ACAN, TAS2R38, WNT2, PHYHIPL, DKK4, DUSP27, and ABCA12. The top 10 down-regulated genes were SFRP2, CHRDL1, KBTBD12, RERGL, DPP10, CLCA4, GREM2, TMIGD1, FEV, and OTOP3. Wnt signaling pathway and extracellular matrix (ECM) were up-regulated in CRA. Three hub genes including WNT2, WNT5A, and SFRP1 were filtered out via Cytoscape. Further RT-qPCR and immunohistochemistry confirmed that WNT2 was highly expressed in CRA. The area under the ROC curve (AUC) at 0.98 indicated the expression level of WNT2 as a candidate to differ CRA from HPP. Our study suggests Wnt signaling pathway and ECM are enriched in CRA, and WNT2 may be used as a novel biomarker for distinguishing CRA from HPP and preventing the malignance of CRA.
Sections du résumé
BACKGROUND
BACKGROUND
Colorectal adenoma (CRA) is a classical premalignant lesion, with high incidence and mainly coexisting with hyperplastic polyp (HPP). Hence, this study aimed to distinguish CRA from HPP by molecular expression profiling and advance the prevention of CRA and its malignance.
METHODS
METHODS
CRA and paired HPP biopsies were collected by endoscopy. Through RNA-sequencing (RNA-seq), the differentially expressed genes (DEGs) were obtained. Functional enrichment analysis was performed based on the DEGs. The STRING database and Cytoscape were used to construct the protein-protein interaction (PPI) network and perform module analysis. Hub genes were validated by real-time quantitative PCR (RT-qPCR) and immunohistochemistry. The ROC curve was drawn to establish the specificity of the hub genes.
RESULTS
RESULTS
485 significant DEGs were identified including 133 up-regulated and 352 down-regulated. The top 10 up-regulated genes were DLX5, MMP10, TAC1, ACAN, TAS2R38, WNT2, PHYHIPL, DKK4, DUSP27, and ABCA12. The top 10 down-regulated genes were SFRP2, CHRDL1, KBTBD12, RERGL, DPP10, CLCA4, GREM2, TMIGD1, FEV, and OTOP3. Wnt signaling pathway and extracellular matrix (ECM) were up-regulated in CRA. Three hub genes including WNT2, WNT5A, and SFRP1 were filtered out via Cytoscape. Further RT-qPCR and immunohistochemistry confirmed that WNT2 was highly expressed in CRA. The area under the ROC curve (AUC) at 0.98 indicated the expression level of WNT2 as a candidate to differ CRA from HPP.
CONCLUSION
CONCLUSIONS
Our study suggests Wnt signaling pathway and ECM are enriched in CRA, and WNT2 may be used as a novel biomarker for distinguishing CRA from HPP and preventing the malignance of CRA.
Identifiants
pubmed: 34477243
doi: 10.1002/jcla.23961
pmc: PMC8529141
doi:
Substances chimiques
WNT2 protein, human
0
Wnt2 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23961Subventions
Organisme : National Key Science and Technology Project of China
ID : 2018YFC2000500-03
Organisme : Shanghai Municipal Key Clinical Specialty
ID : shslczdzk05903
Organisme : National Natural Science Foundation of China
ID : 81630016
Informations de copyright
© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.
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