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Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer

  • Zhang, Meng1, 2
  • Zhou, Zhou1, 2, 3
  • Pan, Xue-kai1, 2
  • Zhou, Yun-jiao1, 2
  • Li, Hai-ou1, 2
  • Qiu, Pei-shan1, 2
  • Zhang, Meng-na1, 2
  • Peng, Ru-yi1, 2
  • Wang, Hai-zhou1, 2
  • Liu, Lan1, 2
  • Liu, Jing1, 2
  • Zhao, Qiu1, 2
  • 1 Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, China , Wuhan (China)
  • 2 Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China , Wuhan (China)
  • 3 Leiden University Medical Center, Leiden, The Netherlands , Leiden (Netherlands)
Published Article
Cancer Cell International
Springer (Biomed Central Ltd.)
Publication Date
Oct 17, 2020
DOI: 10.1186/s12935-020-01604-1
Springer Nature


BackgroundDue to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC.MethodsOnline databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC.ResultsOncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis.ConclusionA tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.

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