Mass Spectrometric Multiplex Detection of MicroRNA and Protein Biomarkers for Liver Cancer

Abstract

The occurrence of cancers is often accompanied by the abnormal expression of several sorts of biomarkers (e.g., nucleic acids and proteins). The multiplex assessment of them would substantially aid in the early detection and precise diagnosis, which is often hampered by their different detection schemes, different reaction matrix and reagents, and spectral overlapping. Herein, we propose a simple and sensitive mass spectrometric method for the multiplex detection of nucleic acid and protein, in which liver cancer-related biomarkers miRNA 223 and alpha-fetoprotein (AFP) were selected as model analytes. The self-amplification effect of metal atom-based nanoparticle probes can provide high sensitivity in complex serum samples without any additional amplification procedure. The detection limits for the simultaneous detection of miRNA 223 and AFP were 103 (2.1 pM) and 219 amol (0.15 ng/mL), respectively, with high specificity and selectivity. The proposed method is potentially useful for the rapid screening of cancers.

Multiplexed miRNA and Protein Analysis Using Digital Quantitative PCR in Microwell Arrays

“…While these low LODs are promising, the multiplexing capacity of the technique was limited. Other sensors have also been developed for multiplexed miRNA and protein measurements as well as methods employing flow cytometry and inductively coupled plasma mass spectrometry. − However, each of these methods lack the sensitivity to measure ultralow abundance biomolecules or are limited to low degrees of multiplexing. The most promising technology to date for high sensitivity multiplexed measurements is bead-based digital ELISA.…”

Co-Reactive Ligand In Situ Engineered Gold Nanoclusters with Ultra-Bright Near-Infrared Electrochemiluminescence for Ultrasensitive and Label-Free Detection of Carboxylesterase Activity

“…Although alpha-fetoprotein (AFP) is a typical serologic biomarker for HCC in early diagnosis, the detection of AFP cannot efficiently distinguish HCC from other liver diseases because of limited sensitivity or specificity. 3,4 Fortunately, carboxylesterase (CE) (EC 3.1.1.1), one of the most abundant serine hydrolases responsible for the metabolism of various xenobiotics in the human liver, could serve as an efficient serological biomarker candidate for HCC because the difference between HCC and liver cirrhosis is significant compared to that with AFP. 5,6 Currently, commercial kits have been used to determine CE activity with a colorimetric assay, which suffers from a relatively low sensitivity.…”

Hairpin DNA-based electrochemical amplification strategy for miRNA sensing by using single gold nanoelectrodes

“…3 As a non-invasive blood biomarker, miRNAs can be detected in various body fluids, including serum and plasma. 4 Numerous detection methods such as mass spectrometry, [5][6][7][8] fluorescence detection, [9][10][11][12] and electrochemical luminescence method [12][13][14][15] have been developed for miRNA detection with high sensitivity. However, these methods are complex and require special laboratory skills.…”