Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 09 2020
07 09 2020
Historique:
received:
10
01
2020
accepted:
10
08
2020
entrez:
8
9
2020
pubmed:
9
9
2020
medline:
29
12
2020
Statut:
epublish
Résumé
Oral cancer patients experience pain at the site of the primary cancer. Patients with metastatic oral cancers report greater pain. Lack of pain identifies patients at low risk of metastasis with sensitivity = 0.94 and negative predictive value = 0.89. In the same cohort, sensitivity and negative predictive value of depth of invasion, currently the best predictor, were 0.95 and 0.92, respectively. Cancer pain is attributed to cancer-derived mediators that sensitize neurons and is associated with increased neuronal density. We hypothesized that pain mediators would be overexpressed in metastatic cancers from patients reporting high pain. We identified 40 genes overexpressed in metastatic cancers from patients reporting high pain (n = 5) compared to N0 cancers (n = 10) and normal tissue (n = 5). The genes are enriched for functions in extracellular matrix organization and angiogenesis. They have oncogenic and neuronal functions and are reported in exosomes. Hierarchical clustering according to expression of neurotrophic and axon guidance genes also separated cancers according to pain and nodal status. Depletion of exosomes from cancer cell line supernatant reduced nociceptive behavior in a paw withdrawal assay, supporting a role for exosomes in cancer pain. The identified genes and exosomes are potential therapeutic targets for stopping cancer and attenuating pain.
Identifiants
pubmed: 32895418
doi: 10.1038/s41598-020-71298-y
pii: 10.1038/s41598-020-71298-y
pmc: PMC7477576
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
14724Subventions
Organisme : NCI NIH HHS
ID : R01 CA113833
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA163019
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000004
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE019796
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026806
Pays : United States
Organisme : NIDCR NIH HHS
ID : R21 DE026964
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
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