Document Type

Article

Publication Date

8-18-2022

Publication Title

Journal of cancer research and clinical oncology

Abstract

BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population.

OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1).

DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy.

RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042).

CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.

PubMed ID

35982181

ePublication

ePub ahead of print

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.