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Prognostic Significance of SOX9 and Its Combination With RAS and TP53 Mutations Following Colorectal Cancer Liver
Jian-Li Duan1, Lei Wen2, Yan-Yu Cai1
1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P.R. China.
Summary
Genetic mutations in SOX9, RAS, and TP53 predict outcomes in colorectal liver metastases (CRLM). SOX9 mutations worsen prognosis and offer a potential therapeutic target for CRLM patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Genetic mutations significantly influence prognosis in patients with colorectal liver metastases (CRLM).
- Previous research often relied on small gene panels, limiting comprehensive prognostic analysis.
- High-throughput sequencing offers a more extensive approach to identifying prognostic genetic markers.
Purpose of the Study:
- To identify gene mutations associated with prognosis in CRLM patients using high-throughput sequencing.
- To investigate the relationship between SOX9 mutation, its expression, and its role in tumor progression.
- To develop a prognostic model incorporating key genetic mutations for CRLM patients.
Main Methods:
- Next-generation sequencing of 1021 genes in 283 colorectal cancer (CRC) patients.
- Cox models for identifying overall survival (OS)-associated mutations, validated in external cohorts.
- In vitro and in vivo functional studies using lentiviral shRNA to assess SOX9's pro-tumorigenic role.
Main Results:
- SOX9 mutations were significantly associated with a worse prognosis in CRLM patients.
- SOX9, RAS, and TP53 mutations were identified as independent prognostic factors.
- A combination of SOX9, RAS, and TP53 mutations showed a stronger correlation with poor prognosis.
- SOX9 mutations correlated with increased expression, and SOX9 silencing inhibited CRC proliferation and migration.
- Findings were validated in independent BJCH and MSKCC cohorts.
Conclusions:
- SOX9 mutations are a significant negative prognostic factor in CRLM.
- SOX9 represents a potential therapeutic target for CRLM.
- A prognostic model including RAS, TP53, and SOX9 mutations can improve outcome prediction for CRLM patients.
