2628. Frequent Amplification and Overexpression of PSMA in Triple-Negative Breast Cancer From Cancer Genome Analysis
Authors* Denotes Presenting Author
Wenhui Zhou *;
Stanford University Medical Center
Sumit Halder;
Indx Technology Inc
Sanna Herwald;
Stanford University Medical Center
Gowhar Shafi;
Indx Technology Inc
Mohan Uttarwar;
Indx Technology Inc
Sirish Kishore;
Stanford University Medical Center
Objective:
PSMA overexpression is commonly observed in nonprostate solid tumors, suggesting that PSMA-targeting radiotracers may have an expanded utility beyond their original FDA indications. The objective of this study is to interrogate the genomic alterations and expression patterns of PSMA in triple-negative breast cancer (TNBC), which currently lacks a biological target for molecular imaging and therapy.
Materials and Methods:
The Cancer Genome Atlas (TCGA) provides comprehensive genomic data and molecular features for approximately 33 cancer types. In this work, we analyzed the somatic copy number status, and transcriptomic and protein expressions of FOLH1 (gene name of PSMA) in all breast cancer subtypes from approximately 1000 breast cancer cases. Putative copy-number alteration of FOLH1 was based on GISTIC 2.0 values, and relative FOLH1 mRNA and PSMA expression values were based on z-scores using the default threshold (2 SDs from the mean). Data were analyzed using one-way ANOVA across multiple molecular subtypes of breast cancer. The Kaplan-Meier method was used to compute relapse-free and distant metastasis-free survival.
Results:
Molecular subtype classification revealed that FOLH1 is more frequently amplified in TNBC (32%) compared to ER+/PR+ and HER2+ breast tumors (16% and 17%, respectively, with p < 0.01). Additionally, FOLH1 expression was more highly expressed in TNBC compared to other subtypes of breast cancer (p < 0.001). Interestingly, FOLH1 expression is negatively correlated with estrogen receptor (ESR1) and progesterone receptor (PR) expression. Consistent with these results, the level of PSMA protein was significantly higher in TNBC compared to other subtypes of breast cancer (p < 0.05). Lastly, FOLH1 expression is associated with favorable relapse-free and distant metastasis free-survival in patients with TNBC.
Conclusion:
There is significant overexpression of the gene copies, RNA transcript, and protein of PSMA in the TNBC subtype compared to other breast cancer subtypes. PSMA expression also correlates with positive cancer survival outcomes in patients with TNBC. This preclinical exploratory study provides a molecular basis of using PSMA-targeted radiopharmaceuticals for TNBC. Future clinical trials should be prioritized to investigate the putative diagnostic, therapeutic and prognostic value of PSMA patients with TNBC.
