Digital Spatial Profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer

Samaneh Eickelschulte^1,2Adam Kaczorowski²Florian Janke¹Anja Lisa Riediger^1,2Olga Lazareva¹Sarah Böning²Glen Kristiansen³Constantin Schwab²Albrecht Stenzinger²Holger Sültmann¹Stefan Duensing²Anette Duensing^2*Magdalena Görtz^1,2*

• ¹German Cancer Research Center (DKFZ), Heidelberg, Germany
• ²Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany
• ³University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany

Background: Prostate cancer (PCa) is a highly heterogeneous disease, ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promising new approach to aid PCa risk stratification is digital spatial profiling (DSP) of PCa tissue.Methods: A total of 94 regions of interest from 38 PCa patients at first diagnosis were analyzed for the expression of 44 proteins, including components of the PI3K/AKT, MAPK, and cell death signaling pathways as well as immune cell markers. An additional validation cohort consisting of 154 PCa patients with long-term follow-up data was analyzed using immunohistochemistry (IHC) to assess the consistency of the identified biomarkers across a larger sample set. Results: DSP identified the proliferation marker Ki-67 and phospho-c-Jun N-terminal protein kinase (p-JNK), a member of the MAPK signaling pathway, as significantly upregulated proteins in aggressive PCa (Gleason grades 4 or 5) compared to indolent disease (Gleason grade 3) (p<0.05). The upregulation of p-JNK was confirmed by IHC. High p-JNK expression was associated with a shorter time to biochemical recurrence (log-rank, p=0.1). Conclusion: Our results indicate that p-JNK may contribute to PCa progression and serve as an early biomarker for aggressive PCa stratification. Identifying this biomarker through DSP could be crucial in advancing disease management and addressing the critical unmet need for more targeted therapies in the treatment of PCa. Further studies are warranted to evaluate the role of p-JNK in PCa progression.