Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer.
Aged
Biomarkers, Tumor
/ genetics
Cell Adhesion Molecules
/ genetics
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ diagnosis
Neural Cell Adhesion Molecule L1
/ genetics
Prognosis
Stomach Neoplasms
/ diagnosis
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
30
04
2019
accepted:
29
10
2019
revised:
09
10
2019
pubmed:
23
11
2019
medline:
20
6
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression. We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo. L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis. L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.
Sections du résumé
BACKGROUND
L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression.
METHODS
We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo.
RESULTS
L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis.
CONCLUSION
L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.
Identifiants
pubmed: 31754264
doi: 10.1038/s41416-019-0646-8
pii: 10.1038/s41416-019-0646-8
pmc: PMC6964673
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell Adhesion Molecules
0
L1CAM protein, human
0
Neural Cell Adhesion Molecule L1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1058-1068Références
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