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

• Published in: Neuromolecular medicine Vol. 24; no. 3; pp. 320 - 338
• Main Authors: Islam, Barira, Stephenson, John, Young, Bethan, Manca, Maurizio, Buckley, David A., Radford, Helen, Zis, Panagiotis, Johnson, Mark I., Finn, David P., McHugh, Patrick C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2022; Springer Nature B.V
• Subjects: Biomarkers; Biomedical and Life Sciences; Biomedicine; Chronic pain; Comparative analysis; DNA microarrays; Gene expression; Internal Medicine; Myc protein; Neuralgia; Neurology; Neurosciences; Original Paper; Pain; Pain perception; Potassium channels (inwardly-rectifying); Stat1 protein; TLR4 protein; Toll-like receptors; Transcriptomics; Biomarkers; Affymetrix microarray; Inflammation; AUROC curve analysis; Neuropathic; Chronic pain
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-021-08694-8

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)).