Validating METCAM/MUC18 as a Novel Biomarker to Predict the Malignant Potential of Prostate Cancer at an Early Stage by Using a Modified Gold Nanoparticles-Based Lateral Flow Immunoassay.

Jui-Chuang Wu,Guang-Jer Wu,Yin-Huan Chuang,Vincent F.-S Tsai,Chia-Chi Hsieh,Yu-Chun Wei,Yuan-Hung Pong,Yenn-Rong Su

doi:10.3390/diagnostics11030443

Abstract

(1) Background: To further validate METCAM/MUC18 as a diagnostic biomarker for prostate cancer, a modified Lateral Flow Immune Assay (LFIA) with increased sensitivity and specificity was designed by taking advantage of the extremely high affinity between biotin and streptavidin and used. (2) Methods: The combination of a commercial biotinylated rabbit antibody (EPP11278), or the home-made biotinylated chicken antibody, and the nano-gold conjugated home-made chicken antibody or a commercial rabbit antibody (EPP11278), had the higher sensitivity and specificity in this modified LFIA to establish calibration curves from the two recombinant METCAM/MUC18 proteins and were used for determining METCAM/MUC18 concentrations in serum specimens from normal individuals, benign prostatic hyperplasia (BPH) patients, prostatic intraepithelial neoplasia (PIN) patients, prostate cancer patients with various Gleason scores, and treated patients. (3) Results: Data obtained by this modified LFIA were statistically better than traditional LFIA and prostate-specific antigen (PSA) test. Interestingly, serum METCAM/MUC18 concentrations were higher in pre-malignant PIN patients than prostate cancer patients and both were higher than normal individuals, BPH patients, and treated patients. Serum METCAM/MUC18 concentrations were directly proportional to most serum PSA. (4) Conclusions: Elevated serum METCAM/MUC18 concentrations may be used for predicting the malignant potential of prostate cancer at an early premalignant (PIN) stage, which is not achievable by the current PSA test.

Highlights

Prostate cancer is the top-leading cause of cancer in males and one of the major causes of cancer death in the world [1]
To identify possible the antibodies with the best specificity and sensitivity, Western blot assay method was used to analyze our home-made chicken antibody and two polyclonal rabbit antibodies from commercial sources for their abilities to recognize the full size huMETCAM/MUC18 protein in the whole cell lysates from various prostate cancer cell lines and the respective recombinant proteins that contain different epitopes
We have successfully developed reliable, only the use of metastasis regulating CAM (METCAM)/MUC18 as a diagnostic biomarker for predicting the malignant cost-effective test to prove the use of METCAM/MUC18 as a diagnostic bipotentialfor of prostate cancer, and better than aoftraditional teststhan in that omarker predicting the malignant potential prostate cancer, butthe better a the elevated serum used to serum predictMETCAM/MUC18 the malignant propensity traditional andMETCAM/MUC18 the prostate-specific antigen (PSA) tests in thatcan thebeelevated can be used to predict the malignant propensity of prostate cancer at the premalignant (PIN)

Summary

Introduction

Prostate cancer is the top-leading cause of cancer in males and one of the major causes of cancer death in the world [1]. Majority of prostate cancer is indolent; about 1/10 of prostate cancer are aggressive, from which the patients may succumb to death within one year of the first diagnosis [2,3]. The most common diagnosis test for the cancer is to detect an elevated serum prostate-specific antigen (PSA). The elevated level of PSA in the serum is not always prognostic of the correct pathologic stage of the cancer or the presence of an indolent or a metastatic disease; it results in at least 20–25% of false diagnosis [4]. To find a better diagnostic marker for accurate predicting the malignant propensity of prostate cancers is still an urgent need. The new diagnostic marker should at least compensate for, or even better to replace the present serum PSA test. We have previously showed that METCAM/MUC18, an immunoglobulin-like cell adhesion molecule [9], is capable of driving the spread of prostate cancer to multiple organs [9,10,11,12,13,14,15,16,17]

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