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. 2021 Aug 2;21(1):884.
doi: 10.1186/s12885-021-08621-x.

Upregulated NLGN1 predicts poor survival in colorectal cancer

Qian Yu #  1 , Xiaojie Wang #  2 , Yinghong Yang  3 , Pan Chi  4 , Jianping Huang  1 , Shengliang Qiu  1 , Xin Zheng  1 , Xiaowen Chen  1
Affiliations

Upregulated NLGN1 predicts poor survival in colorectal cancer

Qian Yu et al. BMC Cancer. .

Abstract

Background: Neuroligin1 (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.

Methods: We 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).

Results: Increased 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.

Conclusions: This study is the first to implicate and verify NLGN1 as a new poor prognostic marker for CRC.

Keywords: Colorectal cancer; NLGN1; Survival.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The workflow of this study
Fig. 2
Fig. 2
The relationship between NLGN1 expression and clinical characteristics of CRC patients. NLGN1 mRNA was upregulated in CRC tissues compared with that in adjacent normals in (A) GSE32323 dataset and at the protein level in (B) our cohort. C The patients with perineural invasion had significantly higher NLGN1 expression than those without perineural invasion. D NLGN1 expression level was significantly higher in microsatellite stable (MSS) patients compared with that in microsatellite instable (MSI) patients
Fig. 3
Fig. 3
Representative images of NLGN1 immunohistochemical analysis in CRC patients in our centre (magnification × 200). A-B Negative-weakly NLGN1 expression in CRC tissue; C Illustrations of NLGN1 protein expression in sections of non-cancerous mucosa (five-pointed star) adjacent to tumors (triangle); D-E Positive-strongly positive NLGN1 expression in CRC tissue; F Illustrations of NLGN1 protein expression in ganglion cells (arrowhead)
Fig. 4
Fig. 4
Illustrations of CRC cells (star) with positive NLGN1 protein expression invading nerve bundles in the perineural space (triangle) (magnification × 200). A Hematoxylin-eosin staining; B Immunohistochemical staining
Fig. 5
Fig. 5
Increased NLGN1 expression predicted worse overall survival in CRC patients from A GSE24551, B GSE39582, and C TCGA. Higher NLGN1 levels were associated with significantly decreased recurrence-free survival rates in D GSE39582 and disease-free survival rates in E patients in our centre
Fig. 6
Fig. 6
The mechanism by which NLGN1 is upregulated in CRC. A There was no association between the methylation level and mRNA expression; B Mutation was not associated with NLGN1 mRNA expression. C No association between the copy number and NLGN1 mRNA expression was observed; D Mutation in NLGN1 was relatively rare with a prevalence of only 1.6% in CRC samples
See this image and copyright information in PMC

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