Related Experiment Video
Updated: Apr 23, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts
Natalie K Rynkiewicz1, Clare G Fedele, Karen Chiam
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
Background:
Phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in prostate carcinoma due to the loss of tumor suppressor PTEN, which leads to increased Akt activity. Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma. However, uncertainty exists regarding the association of INPP4B expression and biochemical and clinical relapse of prostate carcinoma.
Methods:
INPP4B expression in benign prostate acini was analyzed by co-immunofluorescence with cytokeratins (CK) 5, 8, 19, androgen receptor (AR), c-MET, chromogranin A and Ki67. INPP4B expression in prostate carcinoma was analyzed in two independent cohorts (n = 406). The association of INPP4B with biochemical and clinical prostate carcinoma relapse was assessed by Kaplan-Meier and Cox proportional hazards modeling.
Results:
INPP4B was expressed in luminal epithelium within benign ducts, and was highly expressed in CK5+/CK8+/CK19+/AR-/c-MET+/Ki67- intermediate cells in proliferative inflammatory atrophic acini. Overall, INPP4B expression was reduced in prostate carcinoma compared to benign epithelium. Absent/low INPP4B expression was associated with reduced biochemical relapse-free survival (P = 0.01) and increased risk of clinical relapse (P = 0.01). Absence of INPP4B expression was an independent predictor of clinical relapse free survival (P = 0.004) when modeled with Gleason score (P = 0.027) and pathologic stage (P = 0.07).
Conclusions:
INPP4B is highly expressed in intermediate cells within proliferative inflammatory atrophic ducts, and expression is reduced in prostate carcinoma. Absence of INPP4B expression is associated with poor outcome following radical prostatectomy, and represents an independent prognostic marker of prostate carcinoma clinical recurrence.
Insights
Reduced INPP4B expression in prostate cancer is linked to higher recurrence rates. Absence of INPP4B indicates a poor prognosis and serves as an independent marker for clinical relapse after prostatectomy.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- The Phosphoinositide 3-kinase (PI3K)/Akt pathway is often hyperactivated in prostate cancer, partly due to PTEN loss.
- INPP4B, a negative regulator of the PI3K/Akt pathway, shows reduced expression in prostate carcinoma, but its prognostic significance is unclear.
Purpose of the Study:
- To investigate the expression pattern of INPP4B in benign and malignant prostate tissues.
- To determine the association between INPP4B expression and biochemical and clinical relapse in prostate cancer patients.
Main Methods:
- INPP4B expression analyzed via co-immunofluorescence in benign prostate acini.
- INPP4B expression evaluated in two independent prostate carcinoma cohorts (n=406).
- Kaplan-Meier and Cox proportional hazards models used to assess relapse-free survival.
Main Results:
- INPP4B expression was reduced in prostate carcinoma compared to benign epithelium.
- Low or absent INPP4B expression correlated with reduced biochemical relapse-free survival (P=0.01) and increased clinical relapse risk (P=0.01).
- Absence of INPP4B independently predicted clinical relapse-free survival (P=0.004), outperforming Gleason score and pathologic stage.
Conclusions:
- INPP4B is downregulated in prostate carcinoma.
- Absence of INPP4B expression is associated with adverse outcomes post-prostatectomy.
- INPP4B serves as a significant independent prognostic marker for prostate cancer recurrence.
