dc.contributor.author | Porter, RJ | |
dc.contributor.author | Murray, GI | |
dc.contributor.author | Hapca, S | |
dc.contributor.author | Hay, A | |
dc.contributor.author | Craig, SG | |
dc.contributor.author | Humphries, MP | |
dc.contributor.author | James, JA | |
dc.contributor.author | Salto-Tellez, M | |
dc.contributor.author | Brice, DP | |
dc.contributor.author | Berry, SH | |
dc.contributor.author | McLean, MH | |
dc.coverage.spatial | Switzerland | |
dc.date.accessioned | 2024-01-12T15:54:33Z | |
dc.date.available | 2024-01-12T15:54:33Z | |
dc.date.issued | 2023-03-20 | |
dc.identifier | cancers15061865 | |
dc.identifier.citation | Cancers, 2023, 15 (6), pp. 1865 - | |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6108 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.doi | 10.3390/cancers15061865 | |
dc.identifier.doi | 10.3390/cancers15061865 | |
dc.description.abstract | New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4+ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3+ (p < 0.001) and ICOS+ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8+ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an 'immune cold' tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC. | |
dc.format | Electronic | |
dc.format.extent | 1865 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI | |
dc.relation.ispartof | Cancers | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | HMGB1 | |
dc.subject | colorectal cancer | |
dc.subject | cytokine | |
dc.subject | lymphocytes | |
dc.subject | mismatch repair | |
dc.subject | therapy | |
dc.title | Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an 'Immune Cold' Phenotype Associated with Poor Survival. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-03-13 | |
dc.date.updated | 2024-01-12T12:49:55Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.3390/cancers15061865 | |
rioxxterms.licenseref.startdate | 2023-03-20 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36980751 | |
pubs.issue | 6 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology | |
pubs.organisational-group | ICR/ImmNet | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.3390/cancers15061865 | |
pubs.volume | 15 | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Manuel Salto-Tellez) on 2024-01-12. Deposit type is initial. No. of files: 1. Files: Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Prot.pdf | |