Screening of Key Driver and Recurrence Prediction Gene SLC12A2 in Duodenal Papillary Adenoma via WGCNA Combined With Pseudo-time Analysis
10.3969/j.issn.1008-7125.2025.02.002
- VernacularTitle:WGCNA联合拟时序分析筛选十二指肠乳头腺瘤关键驱动和复发预测基因SLC12A2
- Author:
Chengfei JIANG
1
;
Pin WANG
1
;
Pei CAI
1
;
Jingjing WEI
1
;
Lei WANG
1
;
Xiaoping ZOU
1
Author Information
1. 南京大学医学院附属鼓楼医院消化内科(210008)
- Publication Type:Journal Article
- Keywords:
Duodenal Papillary Adenoma;
SLC12A2;
Weighted Gene Co-Expression Network Analysis;
Pseudo-Time Analysis;
Biological Markers
- From:
Chinese Journal of Gastroenterology
2025;30(2):73-81
- CountryChina
- Language:Chinese
-
Abstract:
Background:Duodenal papillary adenoma is a benign tumor with relatively low incidence but significant carcinogenesis potential.Despite the minimal invasiveness and low complication rate,endoscopic papillectomy is associated with a definite risk of recurrence for duodenal papillary adenoma.Investigating the driver genes of duodenal papillary adenoma and establishing predictive models for recurrence and malignant progression could facilitate the precision medicine.Aims:To identify the key driver genes for tumor occurrence,carcinogenesis and recurrence in duodenal papillary adenoma by integrating multi-dimensional bioinformatics approaches based on transcriptomics data,and validate clinically.Methods:Expression profiles of duodenal papillary adenoma and adenocarcinoma were obtained from the GEO database(including data sets GSE189035,GSE94919,GSE111156,and GSE102208).Differentially expressed genes(DEGs)between adenomatous and normal tissues were screened.Weighted gene co-expression network analysis(WGCNA)and pseudo-time analysis were combined to identify the core genes exhibiting an"initial rise followed by decline"expression pattern during the dynamic progression from normal tissue to adenoma and adenocarcinoma.Functional annotation,immune microenvironment profiling,and protein-protein interaction network analysis were performed to explore the tumor-promoting mechanisms of these core genes.Clinical validation was conducted using immunohistochemistry to estimate the gene expression level and its relationship with tumor recurrence.Results:A total of 469 common DEGs were identified.WGCNA revealed that the blue module(including 1 051 genes)was associated with adenoma development and progression(Cor=-0.29,0.15,and 0.11 for normal tissue,adenoma,and adenocarcinoma,respectively).Intersection with DEGs pinpointed four key genes:SLC12A2,BEST4,SLC37A2,and SOAT2.Pseudo-time analysis demonstrated that only SLC12A2 maintained sustained high expression in both adenoma and adenocarcinoma tissues.KEGG enrichment analysis indicated that SLC12A2 was linked to various malignant pathways(e.g.,PD-1/PD-L1 signaling pathway),and its high expression correlated with the reduced immune cell infiltration(e.g.,γδ T cells,CD8+T cells,etc.).Clinical validation by immunohistochemistry confirmed the trend of initial upregulation and subsequent downregulation of SLC12A2 expression in normal,adenoma,and adenocarcinoma tissues.Patients with tumor recurrence showed higher SLC12A2 expression level(P=0.004);likewise,SLC12A2 high expression was associated with an elevated recurrence risk(P=0.034).Conclusions:SLC12A2 serves as a critical driver of tumorigenesis and progression for duodenal papillary adenoma,and might be a promising biomarker for recurrence prediction.
