The Identification of Blood Biomarkers of Chronic Neuropathic Pain by Comparative Transcriptomics

Barira Islam, John Stephenson, Bethan Young, Maurizio Manca, David Buckley, Helen Radford, Panagiotis Zis, Mark Johnson, Dave Finn, Patrick McHugh

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we recruited 50 chronic pain (neuropathic and nociceptive) and 43 pain-free controls to identify specific blood biomarkers of chronic neuropathic pain (CNP). Affymetrix microarray was carried out on a subset of samples selected 10 CNP and 10 pain-free control participants. The most significant genes were cross-validated using the entire dataset by quantitative real-time PCR (qRT-PCR). In comparative analysis of controls and CNP patients, WLS (P = 4.80 × 10 –7), CHPT1 (P = 7.74 × 10 –7) and CASP5 (P = 2.30 × 10 –5) were highly significant, whilst FGFBP2 (P = 0.00162), STAT1 (P = 0.00223), FCRL6 (P = 0.00335), MYC (P = 0.00335), XCL2 (P = 0.0144) and GZMA (P = 0.0168) were significant in all CNP patients. A three-arm comparative analysis was also carried out with control as the reference group and CNP samples differentiated into two groups of high and low S-LANSS score using a cut-off of 12. STAT1, XCL2 and GZMA were not significant but KIR3DL2 (P = 0.00838), SH2D1B (P = 0.00295) and CXCR31 (P = 0.0136) were significant in CNP high S-LANSS group (S-LANSS score > 12), along with WLS (P = 8.40 × 10 –5), CHPT1 (P = 7.89 × 10 –4), CASP5 (P = 0.00393), FGFBP2 (P = 8.70 × 10 –4) and FCRL6 (P = 0.00199), suggesting involvement of immune pathways in CNP mechanisms. None of the genes was significant in CNP samples with low (< 12) S-LANSS score. The area under the receiver operating characteristic (AUROC) analysis showed that combination of MYC, STAT1, TLR4, CASP5 and WLS gene expression could be potentially used as a biomarker signature of CNP (AUROC − 0.852, (0.773, 0.931 95% CI)).

Original languageEnglish
Number of pages19
JournalNeuroMolecular Medicine
Early online date5 Nov 2021
DOIs
Publication statusE-pub ahead of print - 5 Nov 2021

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