Integrated proteogenomic analysis identifies synuclein gamma as
a key target of the mesenchymal stem-like subtype of triple
negative breast cancer

a 2025

Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; Kateřina JURÁSKOVÁ; David POTĚŠIL et al.

Základní údaje

Originální název

Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer

Autoři

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; Kateřina JURÁSKOVÁ ; David POTĚŠIL; Miloš HOLÁNEK; Vojtěch BYSTRÝ; Rudolf NENUTIL; Roman HRSTKA a Pavel BOUCHAL

Vydání

In book of abstracts of 13th Conference of Czech Mass Spectrometry together with 11th Informal proteomic meeting, 19-21 2025, České Budějovice, 2025

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Organizační jednotka

Přírodovědecká fakulta

Změněno: 3. 2. 2026 14:19, doc. Mgr. Pavel Bouchal, Ph.D.

Anotace

V originále

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. γ-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.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

MUNI/A/1684/2024, interní kód MU

Název: Podpora biochemického výzkumu v roce 2025

Investor: Masarykova univerzita, Podpora biochemického výzkumu v roce 2025

NU22-08-00230, projekt VaV

Název: Proteogenomová klasifikace trojitě negativních nádorů prsu ve vztahu k prognóze a cílené terapii

Investor: Ministerstvo zdravotnictví ČR, Proteogenomová klasifikace trojitě negativních nádorů prsu ve vztahu k prognóze a cílené terapii, Podprogram 1 - standardní

Citovat

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; Kateřina JURÁSKOVÁ; David POTĚŠIL; Miloš HOLÁNEK; Vojtěch BYSTRÝ; Rudolf NENUTIL; Roman HRSTKA a Pavel BOUCHAL. Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer. In In book of abstracts of 13th Conference of Czech Mass Spectrometry together with 11th Informal proteomic meeting, 19-21 2025, České Budějovice. 2025.

@proceedings{2543438,
   author = {Šimoník, Jan and Bouchalová, Pavla and Lapčík, Petr and Jurásková, Kateřina and Potěšil, David and Holánek, Miloš and Bystrý, Vojtěch and Nenutil, Rudolf and Hrstka, Roman and Bouchal, Pavel},
   booktitle = {In book of abstracts of 13th Conference of Czech Mass Spectrometry together with 11th Informal proteomic meeting, 19-21 2025, České Budějovice},
   language = {eng},
   title = {Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer},
   year = {2025}
}

TY  - CONF
ID  - 2543438
AU  - Šimoník, Jan - Bouchalová, Pavla - Lapčík, Petr - Jurásková, Kateřina - Potěšil, David - Holánek, Miloš - Bystrý, Vojtěch - Nenutil, Rudolf - Hrstka, Roman - Bouchal, Pavel
PY  - 2025
TI  - Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer
N2  - 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. γ-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.
ER  -

ŠIMONÍK, Jan; Pavla BOUCHALOVÁ; Petr LAPČÍK; Kateřina JURÁSKOVÁ; David POTĚŠIL; Miloš HOLÁNEK; Vojtěch BYSTRÝ; Rudolf NENUTIL; Roman HRSTKA a Pavel BOUCHAL. Integrated proteogenomic analysis identifies synuclein gamma as a key target of the mesenchymal stem-like subtype of triple negative breast cancer. In \textit{In book of abstracts of 13th Conference of Czech Mass Spectrometry together with 11th Informal proteomic meeting, 19-21 2025, České Budějovice}. 2025.

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