Abstract
BackgroundL1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression.MethodsWe 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.ResultsL1CAM 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.ConclusionL1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.
Highlights
L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression
L1CAM expression was associated with tumour malignancy and poor outcomes in the Formalin-fixed and paraffin-embedded (FFPE) cohort of gastric cancer patients We evaluated associations between protein expression and clinicopathological data in the FFPE cohort
The high-staining group of L1CAM was significantly associated with old age (P = 0.001), advanced T stage (P < 0.0001), presence of venous invasion (p < 0.0001), lymphatic vessel invasion (p < 0.0001), nerve invasion (p < 0.0001), lymph node metastasis (P < 0.0001), and distant metastasis (P < 0.0001) in Gastric cancer (GC) patients in the FFPE cohort (Table 1)
Summary
L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression. 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. 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. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. CONCLUSION: L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC. We systematically evaluated the prognostic impact and biomarker potential of L1CAM expression using various statistical methods and clinical specimens, including both FFPE and fresh frozen samples, and clarified the clinical burden of L1CAM expression in GC patients. We investigated the biological features of L1CAM in GC using a series of in vitro and in vivo experiments
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