PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-10-14 DOI:10.1016/j.cyto.2025.157051

Chao huang, Bingjun Liang, Weizeng Shen

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引用次数: 0

Abstract

Objective

Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.

Methods

Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.

Results

A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (P < 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (R = 0.79, P < 0.001). High expression of COL1A1 tended to reduce overall survival (P = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (P < 0.05).

Conclusion

The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.

Abstract Image

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PAX9和Col1A1可能通过与TGF-β1/Smad通路的相互作用调控结肠癌的进展。

目的：转化生长因子-β1 （TGF-β1）通过下游Smad通路广泛参与晚期癌症的进展，但其潜在机制尚不完全清楚。本项目旨在探讨TGF-β1/Smad通路关键分子与结肠癌进展的关系及其上下游调控机制。方法：从TCGA-COAD、GEO、ENCODE等临床数据库和基因组文库中检索结肠癌患者的临床资料及相关基因表达数据。分析TGF-β1/Smad通路关键分子（TGF-β1、TGF-β1受体、SMAD2/3/4）在结肠癌/癌旁组织样本中的表达水平及其与预后的关系。使用R软件包和RStudio分析结肠癌与正常组织之间差异表达的基因以及Smad2/3结合的启动子区域。JASPAR和GO/KEGG富集用于预测TGF-β1/Smad通路的上游转录因子和下游调控基因。结果：共纳入459例结肠癌患者。不同TGF-β1表达水平显著影响结肠癌患者的总生存期（OS）和无病生存期（DFS） (P)结论：TGF-β1/Smad通路可能与多个上下游靶基因（包括PAX9、VDR、Col1A1）共同调控结肠癌的进展和预后，并与肿瘤分期有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.