Identification of a RIPK2-Regulated Gene Signature as a Candidate Biomarker for RIPK2 Activity and Prognosis in Prostate Cancer
Elgehama, A. M.; Yang, Q.; He, Z.; Ruegg, L. E.; You, S.; Yang, W.
Show abstract
Receptor-interacting protein kinase 2 (RIPK2) has emerged as a promising drug target in various cancers, including prostate cancer (PC). However, the absence of reliable biomarkers to assess RIPK2 activity limits both patient selection for anti-RIPK2 therapies and treatment monitoring. To address this gap, we performed RNA-Seq analysis on PC cell lines (22Rv1, DU145, and PC3) with CRISPR/Cas9-mediated RIPK2 knockout (RIPK2-KO) using two independent guide RNAs. This analysis identified 13 candidate RIPK2-regulated genes, of which eight were validated by reverse transcription quantitative PCR (RT-qPCR). Furthermore, treatment with two distinct RIPK2 inhibitors significantly reduced RIPK2 signature scores in five independent PC cell lines in a dose- and/or time-dependent manner. Clinical association analyses revealed that high RIPK2 signature scores correlate with metastasis and worse biochemical recurrence-free, progression-free, disease-free, and overall survival, outperforming RIPK2 mRNA levels as a prognostic biomarker. This study establishes, for the first time, a RIPK2-regulated gene signature as a potential biomarker for RIPK2 activity and PC prognosis, warranting further validation in clinical specimens to provide a much-needed tool for patient stratification and response monitoring in RIPK2-targeted therapies.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Therapeutically actionable PAK4 is amplified, overexpressed and involved in bladder cancer progression 95%
- ECD, a novel androgen receptor target promotes prostate cancer tumorigenesis by regulating glycolysis 95%
- Disassembly of hemidesmosomes promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin into focal adhesions 94%
Similar papers in this journal
- TPX2 expression promotes sensitivity to dasatinib in breast cancer by activating the YAP transcriptional signaling. 94%
- Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion 93%
- An unbiased high-throughput drug screen reveals a potential therapeutic vulnerability in the most lethal molecular subtype of pancreatic cancer 93%
Similar papers in this journal
- A 'one-two punch' therapy strategy to target chemoresistance in estrogen receptor positive breast cancer 94%
- Clinical Significance of Circulating Tumor Cells in Unresectable Pancreatic Ductal Adenocarcinomas 93%
- Enhancing Chemotherapy Response Prediction via Matched Colorectal Tumor-Organoid Gene Expression Analysis and Network-Based Biomarker Selection 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.