Design and Clinical Verification of Surface-Enhanced Raman Spectroscopy Diagnostic Technology for Individual Cancer Risk Prediction

Abstract

The use of emerging nanotechnologies, such as plasmonic nanoparticles in diagnostic applications, potentially offers opportunities to revolutionize disease management and patient healthcare. Despite worldwide research efforts in this area, there is still a dearth of nanodiagnostics which have been successfully translated for real-world patient usage due to the predominant sole focus on assay analytical performance and lack of detailed investigations into clinical performance in human samples. In a bid to address this pressing need, we herein describe a comprehensive clinical verification of a prospective label-free surface-enhanced Raman scattering (SERS) nanodiagnostic assay for prostate cancer (PCa) risk stratification. This contribution depicts a roadmap of (1) designing a SERS assay for robust and accurate detection of clinically validated PCa RNA targets; (2) employing a relevant and proven PCa clinical biomarker model to test our nanodiagnostic assay; and (3) investigating the clinical performance on independent training ( n = 80) and validation ( n = 40) cohorts of PCa human patient samples. By relating the detection outcomes to gold-standard patient biopsy findings, we established a PCa risk scoring system which exhibited a clinical sensitivity and specificity of 0.87 and 0.90, respectively [area-under-curve of 0.84 (95% confidence interval: 0.81-0.87) for differentiating high- and low-risk PCa] in the validation cohort. We envision that our SERS nanodiagnostic design and clinical verification approach may aid in the individualized prediction of PCa presence and risk stratification and may overall serve as an archetypical strategy to encourage comprehensive clinical evaluation of nanodiagnostic innovations.

Cancer Diagnosis through SERS and Other Related Techniques

“…Specifically, for nucleic acid sequences, direct adsorption onto plasmonic materials through the negatively charged phosphate groups enables direct label-free readout strategies saving time-consuming labeling [45,46]. Koo et al designed a label-free SERS diagnostic technology for differentiating between high-and low-risk prostate cancer (PC) ( Figure 3A) [10]. T2:ERG, PCA3, and KLK2 miRNA (PC specific targets) from urine samples are amplified to enhance SERS intensity, through an isothermal process, which results in the stabilization of native miRNA in double-stranded DNA.…”

“…Copyright Frontiers 2019. Adapted from [10] with permission. Copyright American Chemical Society 2018.…”

“…(A) Urine samples from patients with prostate cancer were collected to further isothermally amplify RNA targets (T2:ERG, PCA3, and KLK2) for being detected by SERS substrates. Adapted with permission from[10]. Copyright American Chemical Society 2018.…”

Label‐free diagnosis for colorectal cancer through coffee ring‐assisted surface‐enhanced Raman spectroscopy on blood serum

“…Specific molecular biomarkers, including cytidine and Mucin‐1 , were detected through SERS for cancer screening. In addition, nucleic acids encoding cancer‐related genetic mutation increase the interest of corresponding SERS‐based analysis over DNA and RNA . Extracellular vesicles carrying various cancer‐relevant analytes were also investigated with SERS to obtain improved diagnostics of tumor tissues .…”

Engineering surface-enhanced Raman scattering strategies for liquid biopsy analyses: a step towards precision medicine in cancer management

“…The LOD was determined to be 5. 192,198,199 The detection sensitivity of mutant alleles using SERS has been shown to be 0.1 %, 198 which is 10-fold higher than that of commercial PCR-based assays (1 %). 200 Additionally, the multiplexing capacity provided by the reported nanotag-based SERS strategy is 6, and may be potentially increased by the biointerference-free probe-based SERS detection requires multiple labeling and detection steps, 196 which needs to be further simplified to improve detection efficiency.…”