Research Paper Volume 12, Issue 21 pp 21992—22018

High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma

Yufang Hou1, *, , Weiqi Wang1, *, , Zifan Zeng1, *, , Wenqiang Gan1, , Silin Lv1, , Tiegang Li1, , Zheng Yan1, , Rixin Zhang1, , Min Yang1, ,

  • 1 State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
* Equal contribution

Received: March 3, 2020       Accepted: August 19, 2020       Published: November 7, 2020
How to Cite

Copyright: © 2020 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Semaphorin 4C (SEMA4C), is an important regulator of axonal guidance and aggravates tumor development. However, the roles and prognostic value of SEMA4C in colorectal cancer (CRC) remain unclear. Here, bioinformatics analyses of transcriptome data from multiple CRC patient datasets and immunohistochemical staining of a CRC tissue microarray (TMA) (n=83) showed that SEMA4C mRNA and protein expression were higher in CRC tissues than normal colorectal tissues. SEMA4C mRNA and protein expression correlated with pathologic stage and metastasis in CRC patients. Higher SEMA4C expression was associated with shorter overall survival, consensus molecular subtype 4 (CMS4), and DNA hypomethylation of SEMA4C in CRC patients. Multivariate Cox regression analyses revealed that SEMA4C expression was an independent prognostic predictor in CRC patients. Gene set expression analysis (GSEA) illustrated that SEMA4C expression had remarkable correlations with epithelial-mesenchymal transition (EMT) as well as hedgehog, Wnt/β-catenin, TGF-β, and Notch signaling pathways. Receiver operating characteristic (ROC) curve analysis demonstrated that SEMA4C expression accurately distinguished between the CMS4 and CMS1-3 subtypes of CRC patients. By inhibiting EMT, SEMA4C silencing reduced in vitro proliferation, migration, and invasion by CRC cells. These findings suggest that SEMA4C is a CMS4-associated gene that enhances CRC progression by inducing EMT.


SEMA4C: semaphorin 4C; CRC: colorectal cancer; CMS: consensus molecular subtype; EMT: epithelial–mesenchymal transition; TCGA: The Cancer Genome Atlas; TMA: tissue microarray; GEPIA: Gene Expression Profiling Interactive Analysis; TIMER: Tumor Immune Estimation Resource; PPI: protein-protein interaction; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: Gene Set Enrichment Analysis; OS: overall survival; TFS: tumor-free survival; PFS: progression-free survival; ROC: receiver operating characteristic.