Non-Coding RNA-Based Biosensors for Early Detection of Liver Cancer

Abstract

Primary liver cancer is an aggressive, lethal malignancy that ranks as the fourth leading cause of cancer-related death worldwide. Its 5-year mortality rate is estimated to be more than 95%. This significant low survival rate is due to poor diagnosis, which can be referred to as the lack of sufficient and early-stage detection methods. Many liver cancer-associated non-coding RNAs (ncRNAs) have been extensively examined to serve as promising biomarkers for precise diagnostics, prognostics, and the evaluation of the therapeutic progress. For the simple, rapid, and selective ncRNA detection, various nanomaterial-enhanced biosensors have been developed based on electrochemical, optical, and electromechanical detection methods. This review presents ncRNAs as the potential biomarkers for the early-stage diagnosis of liver cancer. Moreover, a comprehensive overview of recent developments in nanobiosensors for liver cancer-related ncRNA detection is provided.

Keywords: biosensors; electrochemical; electromechanical; liver cancer; nanomaterials; non-coding RNAs (ncRNAs); optical.

Figure 1

Schematic of liver cancer-associated incidence causes, biomarkers and detection methods.

Figure 2

Schematic of various steps of miRNA biosensor fabrication including: surface functionalization of electrodes such as screen printed electrode (SPE), glassy carbon electrode (GCE), carbon paste electrode (CPE), or indium tin oxide electrode (ITO); immobilization of ss-DNA and further hybridization with complementary miRNA; and signal analysis through electrochemical methods (differential pulse voltammetry (DPV), cyclic voltammetry (CV), Chronoamperometry, and electrochemical impedance spectroscopy (EIS)).

Figure 3

Mechanism of electrochemical DNA detection.

Figure 4

Illustration of label-free electrochemical biosensor based on guanine oxidation [124], reprinted with permission from American Chemical Society.

Figure 5

Schematic diagram of the relay-race electrochemical biosensor. Left panel: the predicted structures and nucleic acid sequences of the H-MB/Bar/3WJ, miR21 and MB/barG [73], reprinted with permission from Elsevier.

Figure 6

Schematic illustration of optical-based DNA biosensor sensing approaches: LSPR, SERS, colorimetric and fluorescence detection.

Figure 7

(a) Schematic diagram of MC colorimetric biosensor for miR-21 detection [143], and (b) schematic illustration of Synthetic procedures of Raman dye-coded Au-NPs using DNA-modified AuNPs as templates and the biotemplating synthesis strategy of AgHMSs using bacteria as template (blue sphere) and ascorbic acid (aa) as Ag reductant agent [75], (a) reprinted with permission from Elsevier, and (b) reprinted with permission from American Chemical Society.

Figure 8

Schematic illustration of miRNA detection mechanism using QCM biosensor [165], reprinted with permission from Royal Society of Chemistry.

Figure 9

Illustration of target binding on the cantilever array surface. Perspective is from inside the fluidic chamber. The laser from the optical beam read out detection method is shown reflecting away from a cantilever surface, out of the chamber, and towards the detector. Differential deflection (Δd) arises between the in situ reference probes and target sensitive probes [70], reprinted with permission from Royal Society of Chemistry.