323P - SPEN: Unraveling breast cancer's genetic symphony — Prognostic significance and therapeutic insights

Background

Split ends (SPEN) gene has emerged as a pivotal factor in breast cancer pathophysiology. SPEN gene is a transcriptional corepressor of the Estrogen receptor alpha (ERα), tumor suppressor gene, and candidate predictive biomarker of tamoxifen response in hormone-dependent breast cancers. Additionally, SPEN regulates primary cilia formation and cell migration in ERα-negative breast cancer cells. In this study we assess the predictive and prognostic role of SPEN gene mutation in Breast Cancer.

Methods

The breast cancer Memorial Sloan Kettering Cancer Center, Cancer cell-2018 (n-1918) cohort was utilized. The cohort and corresponding clinical data was retrieved through cBioportal. Immune cell infiltration was assessed through TIMER2.0 web-based tool.

Results

The observed mutation prevalence in the cohort was (3.1%). SPEN mutations were significantly associated with better survival outcomes indicated by both the time to death (Median: 809 vs. 688 months; p- <0.05) and metastatic recurrence time (median 714 vs. 653 months; p- <0.05) compared to unaltered group. Moreover, the tumor mutation burden was significantly higher in the patient group with SPEN mutations (Median: 0.2 vs. 0.1; p- <0.05). SPEN mutations were significantly associated with a positive receptor status in the primary tumor (p- <0.05). Notably, SPEN mutations were found to be significantly associated (P<0.05) with lower macrophage M2 cell and myeloid derived suppressor cells as well as higher CD8+ T-cell and Natural killer (NK) cells infiltration.

Conclusions

Our Analysis revealed enhanced survival outcomes, elevated tumor mutation burden and receptor percentages associated with SPEN gene mutation in breast cancer. Immune infiltration analysis demonstrated enrichment of CD8+T cell and NK cells along with deprivation of inhibitory immune cells. The findings provide additional validation to the potential significance of SPEN mutations as both a prognostic indicator and a promising therapeutic consideration in the management of breast cancer. Subsequent studies are needed to offer detailed mechanistic explanations into the impact of such mutations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.