WGCNA-identified COL13A1 drives osteosarcoma metastasis and progression via TGF-β signaling

TL;DR

This study identifies COL13A1 as a key gene that promotes osteosarcoma growth and spread through TGF-β signaling.

Contribution

COL13A1 is newly identified as a driver of osteosarcoma progression via TGF-β signaling.

Findings

High COL13A1 expression is linked to poor clinical outcomes in osteosarcoma patients.

COL13A1 promotes tumor proliferation, migration, and bone destruction.

COL13A1 enhances TGF-β signaling through β1 integrin and increases MMP9 and cyclin D1 expression.

Abstract

•Through WGCNA of the TARGET-OS cohort, COL13A1 emerged as a prognostic gene in osteosarcoma.•COL13A1 effectively promoted osteosarcoma proliferation, metastasis, and bone destruction.•COL13A1 enhanced TGF-β signaling through β1 integrin.•The study confirmed the role of COL13A1 in osteosarcoma progression.

Through WGCNA of the TARGET-OS cohort, COL13A1 emerged as a prognostic gene in osteosarcoma.

COL13A1 effectively promoted osteosarcoma proliferation, metastasis, and bone destruction.

COL13A1 enhanced TGF-β signaling through β1 integrin.

The study confirmed the role of COL13A1 in osteosarcoma progression.

Osteosarcoma (OS) is a malignant bone tumor with high incidence of metastasis. However, the molecular landscape of osteosarcoma remains incompletely understood. Weighted gene co-expression network analysis (WGCNA), differential expressed genes (DEGs), Cox regression, gene set enrichment analysis (GSEA), receiver operating characteristic curve (ROC) and survival analysis were conducted to screen potential targets and molecular mechanism for OS. Seven modules were considered to be closely related to the prognosis of OS. Subsequent immunohistochemistry (IHC), survival and ROC analysis indicated that high expression of COL13A1 was seen in OS tissue and was significantly associated with poor clinical outcome. COL13A1 expression may correlate with inhibition of M1 polarization and could serve as a predictor for immunotherapy response. Further cellular experiments showed that the expression of COL13A1 promoted the proliferation, migration and invasion. Besides, high expression of COL13A1 enhanced TGF-β signaling through β1 integrin and upregulated MMP9 and cyclin D1 expression. Finally, the low expression of COL13A1 limited the weight and lung metastasis of tumor, and reduced bone destruction in the orthotopic tumor-bearing model. COL13A1 was identified as a novel regulator of OS progression via TGF-β signaling, suggesting its potential as a therapeutic target pending further validation.

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