Absence of KLK4-KLKP1 Fusion Corroborate with PTEN Loss in Characterizing Men at Higher Risk for Biochemical Recurrence in Middle Eastern Prostate Cancer Cohort
Bibliographic record
Abstract
Abstract Background: KLK4-KLKP1 fusion is a recently described molecular event in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern (ME) population. Objective: We assessed the incidence, characterization, and prognostic value of KLK4-KLKP1 fusion in a ME cohort of men with PCa and assessed the relationship of this marker to commonly known biomarkers (PTEN, ERG, SPINK1). Design, setting and participants: We interrogated a cohort of ME men with localized PCa treated by radical prostatectomy between 2005 and 2015 (n=340). 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 with biochemical recurrence (BCR) post radical prostatectomy.Results and limitations: 51.7% of patients’ samples were positive for KLK4-KLKP1; with the expression more commonly found 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 positivity was associated with ERG positivity and inversely associated with PTEN loss. No association was noticed with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (<50 or ³ 50). When correlating to BCR, only PTEN loss was associated with BCR, and this effect became more pronounced 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 ME vs North American (NA) populations. It is associated with ERG positivity and inversely with PTEN loss. KLK4-KLKP1 positivity showed no association with any clinical or pathological parameters, however, it demonstrated a somewhat protective effect when combined with PTEN status. Patient Summary: KLK4-KLKP1 is a newly discovered biomarker expressed in PCa with a higher incidence in the ME population. KLK4-KLKP1 positivity is associated with certain molecular subtypes (ERG-positive, PTEN intact).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".