Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer
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Cancer Cell International Open Access
PRIMARY RESEARCH
Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer Meng Zhang1,2†, Zhou Zhou1,2,3†, Xue‑kai Pan1,2, Yun‑jiao Zhou1,2, Hai‑ou Li1,2, Pei‑shan Qiu1,2, Meng‑na Zhang1,2, Ru‑yi Peng1,2, Hai‑zhou Wang1,2, Lan Liu1,2, Jing Liu1,2* and Qiu Zhao1,2*
Abstract Background: Due 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. Methods: Online 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. Results: Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regu‑ lated 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 progres‑ sion 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. Conclusion: A 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. Keywords: Biomarker, Colorectal cancer, Neogenin-1, Prognosis
*Correspondence: [email protected]; [email protected] † Meng Zhang and Zhou Zhou contributed equally to this work 1 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan 430071, Hubei Province, China Full list of author information is available at the end of the article
Background The morbidity of colorectal cancer (CRC) is rising sharply in those who are younger than 50 years old. What worries us more is that CRC has ranked the first causes of cancer death in men age 20–49 during 2012 to 2016 [1–3]. Although the 5-year survival rate for patients with CRC has ascended to about 65%, the rate declines to 12% of patients di
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