CREB3L4 – Prostate Cancer

CREB3L4 has emerged as a genetically and functionally compelling candidate implicated in prostate cancer risk. Multiple large‐scale studies have evaluated its role and consistently reported significant associations in prostate tissue and blood, supporting its potential as a biomarker for disease predisposition (PMID:39878408). This summary integrates evidence from transcriptome‐wide analyses, proteome Mendelian randomization, and functional assessments to assist in diagnostic decision‑making, commercial applications, and future publications.

A recent transcriptome‑wide association study analyzed 79,194 prostate cancer cases alongside 61,112 controls. The study identified CREB3L4 among five candidate genes enriched in prostate cancer signaling pathways, thereby providing robust epidemiological support for its involvement (PMID:39878408). Such substantive case numbers lend weight to the overall clinical validity by capturing diverse genetic backgrounds and phenotypic expressions.

Complementary genetic evidence comes from a proteome‑wide Mendelian randomization study. In this study, genetically predicted increased levels of CREB3L4 were significantly associated with elevated prostate cancer risk. This finding was further bolstered by replication in the FinnGen consortium, underscoring the reliability and reproducibility of the association (PMID:39994764). The convergence of transcriptomic and proteomic signals reinforces the genetic basis of this association.

While traditional familial segregation data are not available for CREB3L4, the consistent directions of effect observed in large population‐based analyses serve as a surrogate for segregation. The absence of explicit segregation reports is balanced by the extensive cohort data and multi‐study replication, which together emphasize the gene’s role in disease susceptibility.

Functional studies have provided important insights into CREB3L4 biology. Experimental work, including detailed characterization of its genomic organization and alternative splicing in porcine models, has demonstrated ubiquitous tissue expression with specific isoform patterns. These findings suggest that CREB3L4 may influence cellular processes relevant to prostate biology and tumorigenesis (PMID:18982425). The biological relevance observed in these models supports a mechanistic link between CREB3L4 dysregulation and prostate cancer.

In summary, the integration of large‐scale genetic association studies and supportive functional data builds a strong narrative for CREB3L4 as a prostate cancer risk gene. Although traditional segregation data are limited, the robust evidence from independent cohorts and experimental validation provides high clinical utility. Key take‑home: CREB3L4 constitutes a promising marker for prostate cancer risk stratification and may guide future diagnostic and therapeutic strategies.

References

• The Prostate • 2025 • Transcriptome‑Wide Association Study Identified Novel Blood Tissue Gene Biomarkers for Prostate Cancer Risk PMID:39878408
• Human Genomics • 2025 • Proteome‑wide Mendelian randomization identifies causal plasma proteins in prostate cancer development PMID:39994764
• Molecular Biology Reports • 2009 • Genomic organization, alternative splicing and tissues expression of porcine CREB3L4 gene PMID:18982425

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