Informace o publikaci
Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer
| Autoři | |
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| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Triple-negative breast cancer (TNBC) is an aggressive BC subtype that represents ~15% of cases and is primarily treated with systemic chemotherapy. To identify novel therapeutic targets, we performed a multiomics study using LC-DIA-MS/MS based proteomics, RNA sequencing, and whole-exome sequencing in a set of fresh frozen TNBC tissues, generating an integrated dataset for 96 samples. Hierarchical clustering utilizing the proteomics data for 1,223 most correlated transcript–protein pairs stratified TNBC into seven clusters. Of these, cluster 1 was designated as Mesenchymal stem-like (MSL) based on Gene set enrichment analysis and TNBCtype tool outputs. Within MSL subtype, synuclein gamma (SNCG) emerged as a key protein target, originating from significant upregulation in MSL subtype compared to others (log2FC=1.64, padj=0.0023), its core pathway enrichment, and association with both poor progression-free survival of the patients (PFS; HR=2.542, p=0.005, Cox; p=0.004, log-rank test) and overall survival (OS; HR=2.425, p=0.008, Cox; p=0.006, log-rank test). Functional SNCG validation via CRISPR/Cas9 knockout in MDA-MB-231 cells showed reduced proliferation in SNCG?/? clones in the CCK8 proliferation assay (parental vs. G10, padj=2x10-13; vs. B1, padj=9.08x10-4; vs. B3, padj=4.04x10-9). However, no effect on cell migration capacity has been observed in the scratch assay. This is in good agreement with a previous SNCG association with breast cancer progression and recurrence1 and with promoting proliferation in oral squamous cell carcinoma2. In summary, proteomics-driven, multiomics analysis of TNBC patients identified SNCG as a key protein in the MSL subtype linked to poor PFS and OS, and its association with cancer cell proliferation and growth was functionally validated. References (1) Wu, K.; Quan, Z.; Weng, Z.; Li, F.; Zhang, Y.; Yao, X.; Chen, Y.; Budman, D.; Goldberg, I. D.; Shi, Y. E. Expression of Neuronal Protein Synuclein Gamma Gene as a Novel Marker for Breast Cancer Prognosis. Breast Cancer Res Treat 2007, 101 (3), 259–267. https://doi.org/10.1007/s10549-006-9296-7. (2) Yang, J.; Ren, Z.; Wang, F.; Zheng, J.; Zhuang, Z.; Zeng, Y. ?-Synuclein Promotes Proliferation and Inhibits Apoptosis of Oral Squamous Cell Carcinoma via JAK2/STAT5b Signaling Pathway. Am J Cancer Res 2024, 14 (5), 2408–2423. https://doi.org/10.62347/FLIM3367. |
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