PI3-kinase pathway biomarkers in oral cancer and tumor immune cells.
Biomarkers
/ metabolism
Carcinoma, Squamous Cell
/ metabolism
Female
Humans
Lymphocytes
/ metabolism
Macrophages
/ metabolism
Male
Middle Aged
PTEN Phosphohydrolase
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Retrospective Studies
Signal Transduction
/ physiology
Survival Rate
Survivin
/ metabolism
TOR Serine-Threonine Kinases
/ metabolism
Tongue Neoplasms
/ metabolism
immunology
oral squamous cell carcinomas
phosphatase and tensin homolog (PTEN)
phosphoinositide 3-kinase pathway (PI3-kinase pathway)
tumor infiltrating immune cells
Journal
Head & neck
ISSN: 1097-0347
Titre abrégé: Head Neck
Pays: United States
ID NLM: 8902541
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
20
02
2018
revised:
26
03
2018
accepted:
16
05
2018
pubmed:
18
12
2018
medline:
8
10
2020
entrez:
18
12
2018
Statut:
ppublish
Résumé
This study investigated the hypothesis that phosphoinositide 3-kinase (PI3-kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC). We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3-kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p-Akt, mammalian target of rapamycin (mTOR), phosphorylated-mammalian target of rapamycin (p-mTOR), survivin, and Ki-67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes. Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence-free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23-0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15-0.76, P = .01) on univariate and multicovariate models. We identified a novel, negative prognostic role of PI3-kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI-3 kinase inhibitors for this disease.
Sections du résumé
BACKGROUND
This study investigated the hypothesis that phosphoinositide 3-kinase (PI3-kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC).
METHODS
We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3-kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p-Akt, mammalian target of rapamycin (mTOR), phosphorylated-mammalian target of rapamycin (p-mTOR), survivin, and Ki-67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes.
RESULTS
Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence-free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23-0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15-0.76, P = .01) on univariate and multicovariate models.
CONCLUSIONS
We identified a novel, negative prognostic role of PI3-kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI-3 kinase inhibitors for this disease.
Identifiants
pubmed: 30556200
doi: 10.1002/hed.25350
pmc: PMC6382518
mid: NIHMS969679
doi:
Substances chimiques
BIRC5 protein, human
0
Biomarkers
0
Survivin
0
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
615-622Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097007
Pays : United States
Informations de copyright
© 2018 Wiley Periodicals, Inc.
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