Abstract P2-08-37: The prognostic impact of synaptojanin 2 expression in estrogen receptor α-positive breast cancer patients

Abstract

Background: Synaptojanin 2 (SYNJ2) was reported to be a druggable mediator of metastasis. It is overexpressed and amplified in breast cancer, particularly estrogen receptor α (ERα)-positive breast cancer. SYNJ2 was also shown to promote cell migration and invasion in breast cancer xenograft cultures and lung metastasis in mice. Here, we investigated SYNJ2 mRNA expression in breast cancer patients during long-term follow-up. Materials and methods: A total of 434 invasive breast cancer tissues were analyzed for SYNJ2mRNA expression using TaqMan PCR, and the correlation of this expression with patient clinicopathological factors was determined. We also examined the expression of markers associated with tumor-initiating capacity, such as SNAI1, SNAI2, and VIM. Survival curves were analyzed using the Kaplan–Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: The median follow-up period was 10.7 years. We found positive correlations between high expression of SYNJ2 mRNA and shorter disease-free survival in breast cancer patients (P=0.049), which was limited to ERα-positive patients (P=0.020) and not seen in ERα-negative patients (P=0.863). High SYNJ2 mRNA levels were positively correlated with high tumor grade, ERα negativity, and node positivity. Multivariate analysis indicated that high SYNJ2 mRNA expression was an independent factor for poor disease-free survival in breast cancer patients. Multivariate analysis of poor disease-free survival DFS Mutivariate All patientsp valueHR (95%CI)Tumor size2cm and fewer1540.43151 (Reference) more than 2cm280 1.19 (0.78-1.85)Lymph node metastasisNegative2190.0001 and fewer1 (Reference) Positive184 5.61 (3.59-9.05) Unknown31 2.40 (0.89-5.48)Grade1,22330.38471 (Reference) 3195 1.20 (0.79-1.81) Unknown6 0.17 (1.78-3.49)ER statusPositive3370.02621 (Reference) Negative97 2.06 (1.87-4.07)PgR statusPositive2930.39511 (Reference) Negative141 1.30 (0.70-2.28)SYNJ2 mRNA expressionlow2170.02251 (Reference) high217 1.57 (1.07-2.34) Conclusion:High SYNJ2 expression was shown to be an independent predictive factor of poor prognosis in ERα-positive breast cancer patients. SYNJ2 could therefore be used as a candidate biomarker and therapeutic target in breast cancer. Citation Format: Nishikawa S, Kondo N, Wanifuchi-Endo Y, Hisada T, Uemoto Y, Katagiri Y, Dong Y, Kato H, Takahashi S, Toyama T. The prognostic impact of synaptojanin 2 expression in estrogen receptor α-positive breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-37.

Comprehensive analysis of the expression and prognosis for RAI2: A promising biomarker in breast cancer

“…RAI2 has been proven to suppress early hematogenous dissemination of breast cancer and indicate favorable prognosis by analyzing hundreds of breast cancer patient samples. However, these results need further validation with more patient samples (10,12). Our results showed that high RAI2 expression could be regarded as an independent and favorable prognostic biomarker for BRCA patients, which predicts tumor invasion and metastasis.…”

“…Moreover, RAI2 inhibited AKT signaling to suppress CRC progression, and methylated RAI2 indicated poor prognosis in CRC (11). Some studies used invasive breast cancer tissues to indicate that lower RAI2 mRNA and protein were independent risk factors for lower shorter disease-free survival (DFS), and breast-cancer-specific survival (BCSS) (12). However, there are not sufficient studies to explain the biological function of RAI2 in BRCA.…”