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2025 Dean Metropoulos – PCF Young Investigator Award

NLGN1-NRXN1α as a Predictive Spatial Biomarker for Prostate Cancer Progression and Treatment

Sebnem Ece Eksi, PhD
Oregon Health & Science University (OHSU)

Mentors: Gordon Mills

Description:

  • Prostate cancer is frequently diagnosed as a localized disease, and with the implementation of clinical imaging tools like multiparametric MRI (mpMRI), can often be actively surveilled to avoid unnecessary biopsies. However, a subset of patients ultimately progress to incurable disease, highlighting the urgent need for biomarkers to stratify patients and monitor aggressive cancer progression. 
  • Tumor innervation, in which nerves infiltrate tumors, is a critical driver of prostate cancer growth and metastasis, as nerves can stimulate the proliferation, differentiation, and metastasis of prostate cancer cells and interact with immune cells in the tumor microenvironment. However, its role as a biomarker to stratify clinically significant from indolent disease is understudied.
  • Dr. Eksi’s previous research identified a unique pair of neuronal adhesion molecules, NLGN1 and NRXN1, typically associated with synaptic functions in the central nervous system, to be significantly higher in high-grade localized prostate tumors compared to low-grade tumors.
  • In this project, Dr. Eksi will leverage advanced spatial profiling and deep learning tools to investigate whether NLGN1 and NRXN1 are associated with tumor innervation and immune cell infiltration in tumors and can be used as spatial biomarkers for aggressive prostate cancer progression. 
  • Furthermore, Dr. Eksi will use data from trials and patients under active surveillance with mpMRI vs. those who progressed and underwent radical prostatectomy to validate these as biomarkers for aggressive disease progression. 
  • If successful, this project will validate a new biomarker for predicting disease progression in patients with locally aggressive prostate cancer to improve patient outcomes, and deepen our understanding of prostate cancer biology. 

What this means to patients: While the great majority of patients diagnosed with localized prostate cancer can safely undergo active surveillance or be cured with localized therapy, a subset ultimately progress to lethal disease, emphasizing a need for better tests to preemptively identify these patients. As nerve-infiltration into tumors stimulates prostate cancer progression and metastasis, Dr. Eksi’s project will validate whether a new biomarker based on nerve gene activity in tumors, can accurately identify patients diagnosed with localized prostate cancer, who will ultimately progress, enabling early and effective interventions for these patients.