Abstract
BackgroundThe L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.ResultsL1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.ConclusionsA subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.
Highlights
The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT)
L1CAM expression is correlated with poor overall and disease free survival In the total cohort, L1CAM expression was associated with unfavourable OS (p < 0.001) and PFS (p < 0.001) in univariate analysis
L1CAM expression is correlated with EMT markers In the total cohort L1CAM was positively correlated with slug, both tumoral and stromal vimentin, and inversely with E-cadherin
Summary
The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition. L1CAM protein expression was observed in renal cell cancer, ovarian carcinomas, melanoma, colon cancer, pancreatic cancer, and small cell lung cancer [4,5,6,7,8,9,10,11]. No data of L1CAM are available for non-small cell lung cancer (NSCLC). L1CAM expression activated extracellular signalregulated kinase (Erk)-dependent gene regulation and induced NFB activity conferring increased cell motility and invasion [13,14]
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