Urinary VPAC1: A potential biomarker in prostate cancer

Mansur Aliyu; Ali Akbar Saboor-Yaraghi; Shima Nejati; Behrouz Robat-Jazi; Mansur Aliyu; Ali Akbar Saboor-Yaraghi; Shima Nejati; Behrouz Robat-Jazi

doi:10.3934/Allergy.2022006

AIMS Allergy and Immunology

2022, Volume 6, Issue 2: 42-63. doi: 10.3934/Allergy.2022006

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Review Topical Sections

Urinary VPAC1: A potential biomarker in prostate cancer

1.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-IC, Tehran, Iran
2.
Department of Medical Microbiology and Parasitology, Faculty of Clinical Science, College of Health Sciences, Bayero University, Kano, Nigeria
3.
Student Research Committee, Babol University of Medical Sciences, Babol, Iran
4.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Received: 18 January 2022 Revised: 25 April 2022 Accepted: 10 May 2022 Published: 31 May 2022

Prostate cancer is ranked as the fourth most prevalent cancer commonly diagnosed among males over 40 years of age, according to the WHO Cancer Fact Sheet 2020, and it is additionally a leading cause of cancer mortality among males. The incidence of prostate cancer and mortality varied significantly across the globe. Diagnosis of prostate cancer hinders easier management of cases, and prostate-specific antigen (PSA) use for screening of prostate cancer has poor specificity and sensitivity, thereby yielding overdiagnosis and unnecessary biopsies. Radiologically guided (ultrasound/MRI) prostate biopsy, considered the gold standard, is invasive and can miss a significant number of metastatic cancers. Even though mild, other prostate biopsy complications occur on a large scale, and few severe ones are often recorded. Scientists intensify their search for biomarker(s) for non-invasive diagnosis of prostate cancer using proteomics, metabolomics, genomics, and bioinformatics—urinary biomarkers were uniquely on the lookout. Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptor 1 (VPAC1), which is overexpressed (a thousandfold) in prostate cancer at the onset of oncogenesis and is excreted in the urine on tumor cells, is a contender in the prostate cancer biomarker quest. VPAC1 is ubiquitous, expressed by normal and malignant cells, and interwoven in their cell membranes. Therefore, using urine samples limits the possibility of making the wrong diagnosis, since VPAC1 is not normally excreted in the urine. Nevertheless, studying transmembrane receptors is intricate. However, producing monoclonal antibodies against the N-terminal end of VPAC1 can provide a promising target for designing a non-invasive diagnostic assay for early detection of prostate cancer using a urine sample.
- prostate cancer,
- biomarkers,
- screening test,
- vasoactive intestinal peptide,
- VPAC1 receptor
Citation: Mansur Aliyu, Ali Akbar Saboor-Yaraghi, Shima Nejati, Behrouz Robat-Jazi. Urinary VPAC1: A potential biomarker in prostate cancer[J]. AIMS Allergy and Immunology, 2022, 6(2): 42-63. doi: 10.3934/Allergy.2022006

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Abstract

Prostate cancer is ranked as the fourth most prevalent cancer commonly diagnosed among males over 40 years of age, according to the WHO Cancer Fact Sheet 2020, and it is additionally a leading cause of cancer mortality among males. The incidence of prostate cancer and mortality varied significantly across the globe. Diagnosis of prostate cancer hinders easier management of cases, and prostate-specific antigen (PSA) use for screening of prostate cancer has poor specificity and sensitivity, thereby yielding overdiagnosis and unnecessary biopsies. Radiologically guided (ultrasound/MRI) prostate biopsy, considered the gold standard, is invasive and can miss a significant number of metastatic cancers. Even though mild, other prostate biopsy complications occur on a large scale, and few severe ones are often recorded. Scientists intensify their search for biomarker(s) for non-invasive diagnosis of prostate cancer using proteomics, metabolomics, genomics, and bioinformatics—urinary biomarkers were uniquely on the lookout. Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptor 1 (VPAC1), which is overexpressed (a thousandfold) in prostate cancer at the onset of oncogenesis and is excreted in the urine on tumor cells, is a contender in the prostate cancer biomarker quest. VPAC1 is ubiquitous, expressed by normal and malignant cells, and interwoven in their cell membranes. Therefore, using urine samples limits the possibility of making the wrong diagnosis, since VPAC1 is not normally excreted in the urine. Nevertheless, studying transmembrane receptors is intricate. However, producing monoclonal antibodies against the N-terminal end of VPAC1 can provide a promising target for designing a non-invasive diagnostic assay for early detection of prostate cancer using a urine sample.

Abbreviations

PSA

prostate-specific antigen

VIP

vasoactive intestinal peptide

PACAP

pituitary adenylate cyclase-activating peptide

VPAC1

VIP/PACAP receptor 1

ASR

age-standardized rate

BPH

benign prostatic hypertrophy

DHT

5α-dihydrotestosterone

RTqPCR

quantitative reverse transcription polymerase chain reaction

MRI

magnetic resonance imaging

mp-MRI

multiparametric MRI

DCE-MRI

dynamic contrast-enhanced MRI

DWI-MRI

diffusion-weighted imaging MRI

TRUS

trans-rectal ultrasound scan

ELISA

enzyme-linked immunosorbent assay

PCA3

prostate cancer antigen 3

TMPRSS2

transmembrane protease serine 2

GSTP1

glutathione S-transferase P1

DRE

digital rectal examination

AUC

area under the curve

aHGF

hepatocyte growth factor

IGFBP3

insulin-like growth factor binding protein 3

OPN

Plasma osteopontin

LNCaP

lymph node carcinoma of the prostate

GPCRs

G protein-coupled receptors

RAMPS

receptor activity modifying proteins

7-TMD

seven-transmembrane domain

ECD

extracellular domain

CHO

Chinese hamster ovary

TBP

TATA-box binding protein

COX-2

cyclooxygenase-2

MMP9

metalloproteinase 9

uPA

urokinase plasminogen activator

uPAR

uPA receptor

DAPI

4,6-diamidino-2-phenylindole

adenylyl cyclase

CREB

cAMP response element-binding protein

PKA

phosphokinase A

iNOS

inducible nitric oxide synthase

CBP

CREB binding protein

NF-κβ

nuclear factor-κβ

ERK

extracellular signal-regulated kinase

MEKK1

MAP/ERK kinase (MEK) kinase 1

IRF-1

IFN regulatory factor-1

IKK

inhibitory κβ kinase

BB-LP

bombesin-like peptides

GRPR

gastrin-releasing peptide receptor

PLC

phospholipase C

DAG

diacylglycerol

IP3

1,4,5-triphosphate

PKC

protein kinase C

MAPK

mitogen-activated protein kinase

MAPKK

mitogen-activated protein kinase kinase

ELK

ETS like-1 protein

SRE

serum response element

Conflicts of interest

The authors declare no conflict of interest.

Author contributions

MA conceived the idea and drafted the manuscript. MA, AASY, SN, and BRJ searched for the literature, while MA and SN wrote the manuscript and drew the diagrams. MA, AASY, SN, and BRJ revised the manuscript critically and approved the final draft. AASY supervised the whole process.

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