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Updated: Jun 4, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Molecular Characterization of KLK2 RNA Expression in Prostate Cancer
Rana R McKay1, Shayan S Nazari2, Andrew Elliott2
1University of California San Diego , Moores Cancer Center, San Diego, California.
Purpose:
KLK2 is an androgen-regulated gene critical in prostate cancer biology with multiple KLK2-targeted therapies in clinical development. We investigated KLK2 RNA expression patterns and associations with molecular features to provide context for emerging KLK2-targeted treatments.
Experimental Design:
DNA/RNA next-generation sequencing was performed on 7,078 prostate cancer specimens. KLK2-high/low RNA expression was defined as ≥75th/<25th percentiles (transcripts per million, TPM). KLK2 expression was evaluated across histologic subtypes, disease states, and metastatic sites, with correlative analyses of genomic alterations, RNA signatures, and clinical outcomes.
Results:
KLK2 gene expression varied significantly by histology, with highest levels in adenocarcinoma [8.79 log2(TPM + 1)] and minimal expression in histologic neuroendocrine prostate cancer [0.33 log2(TPM + 1)]. Expression was significantly higher in androgen deprivation therapy (ADT)/androgen receptor pathway inhibitor (ARPI)-sensitive versus ADT/ARPI-exposed tumors [8.97 vs. 8.38 log2(TPM + 1), q < 0.001]. Localized tumors demonstrated higher expression than lymph node [8.93 vs. 8.76 log2(TPM + 1)] or distant metastases [8.23 log2(TPM + 1)], with visceral metastases showing the lowest levels. In the overall cohort, KLK2 expression correlated positively with androgen receptor signaling (r = 0.25-0.47) and negatively with neuroendocrine signaling. High KLK2 expression was associated with significantly improved overall survival (93.9 vs. 74.4 months, hazard ratio 0.68, P < 0.001) in the total cohort, with similar patterns in patients with ADT/ARPI-sensitive and ADT/ARPI-exposed disease.
Conclusions:
This large-scale clinico-genomic analysis reveals distinct KLK2 expression patterns across prostate cancer histologies, tumor sites, and clinical states. These findings provide a molecular framework understanding KLK2 as a therapeutic target in prostate cancer.
Insights
This study reveals KLK2 gene expression varies by prostate cancer type and location. High KLK2 expression correlates with better survival, informing KLK2-targeted therapies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- KLK2 is an androgen-regulated gene vital in prostate cancer.
- Emerging therapies target KLK2, necessitating understanding of its expression patterns.
Purpose of the Study:
- Investigate KLK2 RNA expression patterns in prostate cancer.
- Correlate KLK2 expression with molecular features and clinical outcomes.
Main Methods:
- Analyzed DNA/RNA next-generation sequencing data from 7,078 prostate cancer specimens.
- Defined KLK2-high/low expression using transcripts per million (TPM).
- Evaluated expression across histology, disease states, and metastatic sites; performed correlative analyses.
Main Results:
- KLK2 expression varied significantly by histology, highest in adenocarcinoma, lowest in neuroendocrine prostate cancer.
- Higher KLK2 expression observed in androgen deprivation therapy (ADT)/androgen receptor pathway inhibitor (ARPI)-sensitive vs. exposed tumors.
- High KLK2 expression associated with improved overall survival (93.9 vs. 74.4 months).
- KLK2 expression correlated positively with androgen receptor signaling and negatively with neuroendocrine signaling.
Conclusions:
- Distinct KLK2 expression patterns identified across prostate cancer subtypes and clinical states.
- Findings provide a molecular framework for understanding KLK2 as a therapeutic target.
- KLK2 expression patterns offer context for developing KLK2-targeted therapies.
