SETD7 Expression Is Associated with Breast Cancer Survival Outcomes for Specific Molecular Subtypes: A Systematic Analysis of Publicly Available Datasets

Monteiro, Fatima LilianaUniv Aveiro, Inst Biomed iBiMED, Dept Med Sci, P-3810193 Aveiro, Portugal. (författare)

SETD7 Expression Is Associated with Breast Cancer Survival Outcomes for Specific Molecular Subtypes : A Systematic Analysis of Publicly Available Datasets

QC 20230112
SETD7 is a lysine N-methyltransferase that targets many proteins important in breast cancer (BC). However, its role and clinical significance remain unclear. Here, we used online tools and multiple public datasets to explore the predictive potential of SETD7 expression (high or low quartile) considering BC subtype, grade, stage, and therapy. We also investigated overrepresented biological processes associated with its expression using TCGA-BRCA data. SETD7 expression was highest in the Her2 (ERBB2)-enriched molecular subtype and lowest in the basal-like subtype. For the basal-like subtype specifically, higher SETD7 was consistently correlated with worse recurrence-free survival (p < 0.009). High SETD7-expressing tumours further exhibited a higher rate of ERBB2 mutation (20% vs. 5%) along with a poorer response to anti-Her2 therapy. Overall, high SETD7-expressing tumours showed higher stromal and lower immune scores. This was specifically related to higher counts of cancer-associated fibroblasts and endothelial cells, but lower B and T cell signatures, especially in the luminal A subtype. Genes significantly associated with SETD7 expression were accordingly overrepresented in immune response processes, with distinct subtype characteristics. We conclude that the prognostic value of SETD7 depends on the BC subtype and that SETD7 may be further explored as a potential treatment-predictive marker for immune checkpoint inhibitors.

Stepanauskaite, LinaKarolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden.(Swepub:kth)u1xd7zej (författare)
Williams, Cecilia,Professor,1969-Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden.(Swepub:kth)u1ygqmuy (författare)
Helguero, LuisaDepartment of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal (författare)
Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, P-3810193 Aveiro, Portugal.Science for Life Laboratory, SciLifeLab (creator_code:org_t)

Av författaren/redakt...: Monteiro, Fatima ...; Stepanauskaite, ...; Williams, Cecili ...; Helguero, Luisa

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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