ISL1 serves as a biomarker of metastasis and neuroendocrine neoplasia in multiple tumors. However, the expression and relation of ISL1 to other biomarkers in prostate cancer have not been fully elucidated. Here, we characterize the expression of ISL1 and its partners in PCa and document its association to disease progression and post castration resistance neuroendocrine differentiation.
The expression of ISL1 was interrogated in > 6000 primary samples from the Decipher GRID registry and 250 mCRPC samples to assess its prognostic value and relation to neuroendocrine differentiation.
ISL1 was highly correlated to MEIS genes and other genes related to cell motility. ISL1 down-regulation in PCa was associated with cancer progression, aggressive primary tumors, and metastatic outcome. We found that ISL1 is highly correlated to MEIS genes across multiple primary PCa and mCRPC cohorts. The expression of ISL1 and MEIS genes were significantly and inversely related to metastasis-free survival and lethal disease, and were downregulated in CRPC and hormone naïve metastatic tumors but showed upregulation in neuroendocrine tumors. Co-immunoprecipitation showed MEIS2 and ISL1 interacting with each supporting their role in modulating transcriptional regulation and nominating this complex for potential targeted therapy.
ISL1 complex with MEIS2 serves a critical role in prostate tumor progression and its upregulation in mCRPC/NE provides a rationale for assessing the role of ISL1 and its associated protein in treatment resistance.
Journal of cancer research and clinical oncology. 2021 Apr 16 [Epub ahead of print]
Mohammed Alshalalfa, Hatem Abou-Ouf, Elai Davicioni, R Jeffrey Karnes, Reda Alhajj, Tarek A Bismar
The Prostate Cancer Center, Calgary, AB, Canada., Department of Pathology and Laboratory Medicine, University of Calgary Cumming School of Medicine, Calgary, AB, Canada., Decipher Biosciences Inc, Vancouver, BC, Canada., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Computer Science, University of Calgary, Calgary, AB, Canada., The Prostate Cancer Center, Calgary, AB, Canada. .