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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Integrative genomic profiling identifies MLPH as a candidate gene in prostate cancer
Runyi Wang1,2, Jiayu Wang1,2, Zhiyi Zhao1,2
1Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Frontiers in Medicine
|July 25, 2026
Summary
This study identifies MLPH as a potential prostate cancer (PCa) susceptibility gene by integrating multi-omics data. MLPH expression is linked to tumor characteristics and biological pathways, suggesting its role in PCa development.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Prostate cancer (PCa) is a genetically complex and heterogeneous malignancy.
- Understanding the genetic basis of PCa is crucial for developing targeted therapies.
- Previous studies have identified genetic risk factors, but a comprehensive integration of multi-omics data is needed.
Purpose of the Study:
- To integrate multi-omics data to identify and prioritize candidate genes associated with prostate cancer susceptibility.
- To evaluate the functional and clinical significance of prioritized candidate genes in prostate cancer pathogenesis.
- To pinpoint specific regulatory signals and their relevance within the tumor microenvironment.
Main Methods:
- Integrated prostate cancer Genome-Wide Association Study (GWAS) summary statistics with GTEx v8 expression quantitative trait locus (eQTL) data.
- Performed transcriptome-wide association studies (TWAS) and utilized conditional analysis, MAGMA, fastBAT, SMR, and Bayesian colocalization for signal refinement.
- Incorporated tumor-context cis-eQTL analysis from TCGA-PRAD and assessed candidates using transcriptomic datasets, immunohistochemistry, single-cell RNA-seq, and clinical data.
Main Results:
- Identified 23 consensus candidate genes, with MLPH being the final prioritized candidate through integrative genetic analyses and tumor-context eQTL.
- MLPH expression was significantly associated with its lead variant rs7582964 in PRAD tumor tissues and was upregulated in PCa.
- MLPH expression correlated with histological differentiation, preoperative PSA levels, and genomic risk scores, and was localized to epithelial cells, particularly in tumors.
Conclusions:
- MLPH is prioritized as a candidate susceptibility gene for prostate cancer.
- The study links MLPH's regulatory signal to its expression in tumors, protein evidence, cellular localization, and clinical features.
- MLPH may play a role in prostate cancer biology, particularly concerning vesicle trafficking and tumor differentiation.
