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Updated: Oct 31, 2025
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Transcriptomic analysis of castration, chemo-resistant and metastatic prostate cancer elucidates complex genetic
Sayani Mukherjee1, C Sudandiradoss2
1Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Tamil Nadu, Vellore, 632014, India.
Abstract:
Prostate adenocarcinoma, with its rising numbers and high fatality rate, is a daunting healthcare challenge to clinicians and researchers alike. The mainstay of our meta-analysis was to decipher differentially expressed genes (DEGs), their corresponding transcription factors (TFs), miRNAs (microRNA) and interacting pathways underlying the progression of prostate cancer (PCa). We have chosen multiple datasets from primary, castration-resistant, chemo-resistant and metastatic prostate cancer stages for investigation. From our tissue-specific and disease-specific co-expression networks, fifteen hub genes such as ACTB, ACTN1, CDH1, CDKN1A, DDX21, ELF3, FLNA, FLNC, IKZF1, ILK, KRT13, KRT18, KRT19, SVIL and TRIM29 were identified and validated by molecular complex detection analysis as well as survival analysis. In our attempt to highlight hub gene-associated mutations and drug interactions, FLNC was found to be most commonly mutated and CDKN1A gene was found to have highest druggability. Moreover, from DAVID and gene set enrichment analysis, the focal adhesion and oestrogen signalling pathways were found enriched which indicates the involvement of hub genes in tumour invasiveness and metastasis. Finally by Enrichr tool and miRNet, we identified transcriptional factors SNAI2, TP63, CEBPB and KLF11 and microRNAs, namely hsa-mir-1-3p, hsa-mir-145-5p, hsa-mir-124-3p and hsa-mir-218-5p significantly controlling the hub gene expressions. In a nutshell, our report will help to gain a deeper insight into complex molecular intricacies and thereby unveil the probable biomarkers and therapeutic targets involved with PCa progression.
Insights
This study identifies key genes, transcription factors, and microRNAs involved in prostate cancer progression. Findings highlight potential biomarkers and therapeutic targets for this challenging disease.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Prostate cancer (PCa) presents a significant clinical challenge due to increasing incidence and high mortality.
- Understanding the molecular mechanisms driving PCa progression is crucial for developing effective treatments.
Purpose of the Study:
- To identify differentially expressed genes (DEGs), transcription factors (TFs), microRNAs (miRNAs), and pathways in prostate cancer progression.
- To uncover potential biomarkers and therapeutic targets for advanced prostate cancer.
Main Methods:
- Meta-analysis of multiple prostate cancer datasets (primary, castration-resistant, chemo-resistant, metastatic).
- Construction of tissue-specific and disease-specific co-expression networks to identify hub genes.
- Utilized DAVID, gene set enrichment analysis, Enrichr, and miRNet for pathway and regulatory element identification.
Main Results:
- Fifteen hub genes (e.g., ACTB, CDKN1A, FLNC) were identified and validated.
- FLNC showed the highest mutation frequency, while CDKN1A exhibited the highest druggability.
- Focal adhesion and oestrogen signalling pathways were enriched, suggesting roles in invasiveness and metastasis.
- Specific TFs (SNAI2, TP63, CEBPB, KLF11) and miRNAs (hsa-mir-1-3p, hsa-mir-145-5p, hsa-mir-124-3p, hsa-mir-218-5p) were found to regulate hub gene expression.
Conclusions:
- This comprehensive analysis provides insights into the molecular intricacies of prostate cancer progression.
- Identified hub genes, TFs, and miRNAs represent potential diagnostic biomarkers and therapeutic targets for PCa.
