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

Chao Huang1, Bingjun Liang1, Weizeng Shen1

  • 1Department of Traditional Chinese Medicine, Shenzhen Hospital of Guangdong Provincial People's Hospital (The Second Affiliated Hospital of Shenzhen University), Shenzhen 518100, China.

Cytokine
|October 15, 2025
PubMed
Abstract

Insights

Transforming growth factor-β1 (TGF-β1) and its Smad pathway significantly impact colon cancer survival and stage. Key molecules like PAX9, VDR, and Col1A1 are implicated in its progression and prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Transforming growth factor-β1 (TGF-β1) signaling via the Smad pathway is crucial in cancer progression.
  • The precise mechanisms linking TGF-β1/Smad pathway to colon cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the relationship between TGF-β1/Smad pathway molecules and colon cancer progression.
  • To explore upstream and downstream regulatory mechanisms of this pathway in colon cancer.

Main Methods:

  • Utilized TCGA-COAD, GEO, and ENCODE databases for clinical and gene expression data.
  • Analyzed expression levels of TGF-β1, its receptor, and SMAD2/3/4 in colon cancer tissues.
  • Employed R packages for differential gene expression analysis and promoter binding site identification.
  • Used JASPAR and GO/KEGG for predicting transcription factors and downstream targets.

Main Results:

  • TGF-β1 expression levels significantly correlated with overall survival (OS) and disease-free survival (DFS) in 459 colon cancer patients.
  • Pathway molecule expression varied with cancer stage.
  • Identified 954 genes with Smad2/3 binding sites; PAX9 and VDR showed altered expression in colon cancer.
  • Col1A1 expression strongly correlated with TGF-β1 and was associated with survival outcomes.

Conclusions:

  • The TGF-β1/Smad pathway, along with target genes PAX9, VDR, and Col1A1, plays a role in colon cancer progression and prognosis.
  • Pathway activity is linked to cancer stage and survival, suggesting therapeutic potential.
Keywords:
Colon cancerEpithelial–mesenchymal transitionExtracellular matrixTransforming growth factor-β1Tumor microenvironment

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