Abstract
BackgroundNeuroligin1 (NLGN1) is a main component of excitatory glutamatergic synapses complex and is important for synapse assembly and function. The clinical value of NLGN1 in colorectal cancer (CRC) is not clear.MethodsWe obtained the expression data of 1143 CRC patients from 3 independent Gene Expression Omnibus (GEO) datasets (GSE32323, GSE24551, GSE39582) and The Cancer Genome Atlas (TCGA) to make the comparison of the NLGN1 expression level between CRC tissues and matched noncancerous tissues, and to evaluate its value in predicting survival of CRC patients. At the protein level, these results were further confirmed by immunohistochemical staining of 52 CRC samples in our own centre. Finally, the function of NLGN1 was explored by gene set enrichment analysis (GSEA).ResultsIncreased mRNA and protein levels of NLGN1 expression were associated with worse overall survival or recurrence-free survival in CRC patients from 2 GEO datasets, the TCGA database, and our cohort. In addition, multivariate regression analysis showed that NLGN1 was an independent poor prognostic factor of survival in patients with CRC in TCGA database (OR = 2.524, P = 0.010). Functional analysis revealed that NLGN1 was correlated with function involving the Hedgehog signaling pathway, mismatch repair process, and some material metabolism processes.ConclusionsThis study is the first to implicate and verify NLGN1 as a new poor prognostic marker for CRC.
Highlights
Neuroligin1 (NLGN1) is a main component of excitatory glutamatergic synapses complex and is important for synapse assembly and function
Neuroligin 1 (NLGN1) expression is upregulated in colorectal cancer (CRC) To determine the NLGN1 mRNA levels in CRC samples, we compared the NLGN1 mRNA expression between 17 CRC tissues and matched normals in GSE32323 dataset
The analysis revealed that NLGN1 expression was significantly increased in CRC tissues compared with that in matched mucosa (8.3 ± 0.3 vs. 8.1 ± 0.2, P = 0.032, Fig. 2A)
Summary
Neuroligin (NLGN1) is a main component of excitatory glutamatergic synapses complex and is important for synapse assembly and function. The clinical value of NLGN1 in colorectal cancer (CRC) is not clear. Neuroligin 1 (NLGN1) encodes a trans-synaptic protein that acts as a postsynaptic adhesion molecule involved in the regulation of glutamatergic transmission. NLGN1 mediates transsynaptic binding with neurexin [8] and was known to play a pivotal role in memory formation and modulation of memory strength [9]. The role of NLGN1 in cancer is largely unknown. The expression level of NLGN1 in CRC tissues and its clinical value have never been studied. The aim of this study was to determine NLGN1 expression in CRC tissues and to evaluate its prognostic value
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