PDLIM4 – Prostate Cancer

PDLIM4 has emerged as a candidate biomarker in prostate cancer, with multiple studies demonstrating its aberrant methylation profile in tumor tissues compared to benign samples. In one study, quantitative pyrosequencing revealed that methylation levels of PDLIM4 and other candidate genes were significantly elevated in 48 prostate cancer samples versus 29 benign prostate hyperplasia tissues (PMID:21694441). Similarly, an independent report assessed 32 recurrent primary prostate tumors and found hypermethylation of PDLIM4 among other genes relative to 32 benign controls (PMID:19229700). This convergence of evidence from different cohorts emphasizes the potential diagnostic utility of PDLIM4 methylation status in prostate cancer.

While classical segregation data from familial studies is lacking—likely due to the complex, non‐Mendelian nature of cancer predisposition—the reproducible epigenetic alterations observed across independent studies provide indirect genetic evidence for the gene‐disease association. The absence of reported coding sequence variants in PDLIM4 does not detract from its clinical relevance, as the differential methylation itself serves as a robust molecular marker. Consequently, no HGVS coding variant has been identified for this association.

Genetic evidence is bolstered by these independent multi‐patient studies that consistently report significant differences in PDLIM4 methylation between cancerous and benign tissues. The quantitative data from these studies indicate that altered methylation of PDLIM4 may be instrumental in tumorigenesis, thereby supporting its role as a biomarker. Although the studies do not detail specific coding variants, the epigenetic changes provide a measurable and reproducible genetic alteration associated with prostate cancer.

Functional experiments further illuminate the role of PDLIM4 in prostate cancer biology. One study investigating PDZ domain specificities demonstrated that minimal substitutions can convert the binding properties of related protein domains, suggesting that even subtle changes in PDLIM4 may impact its functional interactions (PMID:31654425). Another study focused on gene regulation in T cells revealed that downregulation of PDLIM4 perturbs cell trafficking mechanisms—a finding that may be extrapolated to tumor cell behavior in prostate cancer (PMID:31393857). Such mechanistic insights underscore the biological plausibility of PDLIM4’s contribution to prostate tumor biology.

Integrating both the multi‐patient methylation data and the functional studies, the evidence converges on a strong association between PDLIM4 dysregulation and prostate cancer. The consistency of these findings across independent cohorts and experimental platforms provides a compelling narrative that supports the clinical relevance of PDLIM4 as a diagnostic marker. Researchers and clinicians may consider further validation studies to refine its utility, with the current data already holding promise for commercial applications in cancer diagnostics.

Key take‑home: The reproducible hypermethylation and functional alterations of PDLIM4 in prostate cancer not only highlight its pathogenetic role but also reinforce its potential as a robust diagnostic biomarker for improved patient stratification.

References

• Disease markers • 2011 • Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing PMID:21694441
• Cancer investigation • 2009 • Hypermethylation of genes for diagnosis and risk stratification of prostate cancer PMID:19229700
• Protein science : a publication of the Protein Society • 2020 • Comprehensive analysis of all evolutionary paths between two divergent PDZ domain specificities PMID:31654425
• The Journal of clinical investigation • 2019 • JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4 PMID:31393857

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