Hub metastatic gene signature and risk score of breast cancer patients with small tumor sizes using WGCNA.

Autor: Chang YT; School of Public Health, National Defense Medical Center, Taipei City, Taiwan., Hong ZJ; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Tsai HH; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Feng AC; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Huang TY; School of Public Health, National Defense Medical Center, Taipei City, Taiwan., Yu JC; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Hsu KF; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Huang CC; Department of Surgery, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.; Comprehensive Breast Health Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei City, 100, Taiwan., Lin WZ; AIoT Center, Tri-Service General Hospital, Taipei City, Taiwan., Chu CM; School of Public Health, National Defense Medical Center, Taipei City, Taiwan., Liang CM; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan., Liao GS; Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City, 114202, Taiwan. liaogs20371@gmail.com.
Jazyk: angličtina
Zdroj: Breast cancer (Tokyo, Japan) [Breast Cancer] 2024 Nov; Vol. 31 (6), pp. 1114-1129. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1007/s12282-024-01627-w
Abstrakt: Background: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices.
Methods: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression.
Results: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3.
Conclusion: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms.
(© 2024. The Author(s).)
Databáze: MEDLINE
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