Identification of novel biomarkers of prostate cancer through integrated analysis

AbstractSensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible “liquid biopsies”. Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in PCa patients and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. The mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supports a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in prostate cancer, which can be exploited for novel biomarkers and therapies.

Download Full-text

AR Splicing Variants and Resistance to AR Targeting Agents

Cancers ◽

10.3390/cancers13112563 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2563

Author(s):

Mayuko Kanayama ◽

Changxue Lu ◽

Jun Luo ◽

Emmanuel S. Antonarakis

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Splice Variants ◽

Treatment Options ◽

Predictive Biomarker ◽

Castration Resistant Prostate Cancer ◽

Treatment Benefit ◽

Novel Biomarkers ◽

The Many ◽

Preclinical And Clinical Studies

Over the past decade, advances in prostate cancer research have led to discovery and development of novel biomarkers and effective treatments. As treatment options diversify, it is critical to further develop and use optimal biomarkers for the purpose of maximizing treatment benefit and minimizing unwanted adverse effects. Because most treatments for prostate cancer target androgen receptor (AR) signaling, aberrations affecting this drug target are likely to emerge following the development of castration-resistant prostate cancer (CRPC), and it is conceivable that such aberrations may play a role in drug resistance. Among the many AR aberrations, we and others have been studying androgen receptor splice variants (AR-Vs), especially AR-V7, and have conducted preclinical and clinical studies to develop and validate the clinical utility of AR-V7 as a prognostic and potential predictive biomarker. In this review, we first describe mechanisms of AR-V generation, regulation and their functions from a molecular perspective. We then discuss AR-Vs from a clinical perspective, focusing on the significance of AR-Vs detected in different types of human specimens and AR-Vs as potential therapeutic targets.

Download Full-text

Circular RNA Expression Profiling Identifies Prostate Cancer- Specific circRNAs in Prostate Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000494870 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1903-1915 ◽

Cited By ~ 18

Author(s):

Qianlin Xia ◽

Tao Ding ◽

Guihong Zhang ◽

Zehuan Li ◽

Ling Zeng ◽

...

Keyword(s):

Prostate Cancer ◽

Polymerase Chain Reaction Analysis ◽

Circular Rna ◽

Differentially Expressed ◽

Pcr Analysis ◽

High Morbidity ◽

Qrt Pcr ◽

Diagnosis And Prognosis ◽

Novel Biomarkers ◽

Rna Expression Profiling

Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.

Download Full-text