Expression of Transforming Growth Factor Beta 1 in Lung Adenocarcinoma and Its Relationship with Circulating Tumour Cells
摘要
To investigate the relationship between the expression of transforming growth factor beta 1 (TGF-β1), epithelial–mesenchymal transition (EMT)-related proteins, circulating tumour cells (CTCs) positivity rate and tumour differentiation degree in lung adenocarcinoma. A prospective study was conducted, including 78 patients with lung adenocarcinoma who underwent surgical resection at our hospital between March 2021 and December 2021. Clinical data, lung adenocarcinoma and adjacent tissues were collected. Western blot, immunohistochemistry and RT-PCR were used to detect the expression of TGF-β1, EMT-related proteins (E-cadherin, vimentin) and mRNA in lung adenocarcinoma. Peripheral blood for CTC analysis was collected within 1 week before surgical resection. Pearson correlation analysis was employed to assess the relationship between TGF-β1, EMT and CTCs. There was a significant correlation between the positive rate of CTCs and the degree of tumour differentiation in patients with lung adenocarcinoma (P < 0.05). The expression of TGF-β1 increased significantly as the degree of differentiation decreased (P < 0.05). It was positively correlated with vimentin expression and negatively correlated with E-cadherin expression (P < 0.05). High expression of TGF-β1 in lung adenocarcinoma promotes EMT and the occurrence of CTCs and is associated with the degree of tumour differentiation.
Graphical AbstractIn 78 treatment of naïve patients with stage I-II lung adenocarcinoma, TGF-β1 expression increased as tumour differentiation declined, accompanied by E‑cadherin downregulation and vimentin upregulation, indicating EMT activation. Preoperative CTC detection using ISET showed a higher CTC-positive rate and exclusive CTC clusters in poorly differentiated tumours, whereas well/moderately differentiated tumours released single CTCs. Transcriptional analysis of CTCs confirmed a TGF-β1-driven EMT signature mirroring the primary tumour. These findings establish a TGF-β1-EMT-CTC axis linking poor differentiation to enhanced CTC shedding and clustering, suggesting a non‑invasive biomarker for early metastatic risk.