J Cancer 2018; 9(13):2374-2379. doi:10.7150/jca.26359

Research Paper

NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis

Guiyang Wu1*, Zaiping Chen1*, Jing Li2*, Fubo Ye1, Guoping Chen1, Qinghao Fan1, Hao Dong1, Shichao Yuan1✉, Xiongwen Zhu1✉

1. Department of General Surgery, Taizhou Municipal Hospital, Medical College of Taizhou University, Taizhou 318000, Zhejiang Province, China.
2. Departments of CyberKnife, Huashan Hospital, Fudan University, Shanghai 200032, China
*Guiyang Wu, Zaiping Chen and Jing Li contribute equally to this work.

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Wu G, Chen Z, Li J, Ye F, Chen G, Fan Q, Dong H, Yuan S, Zhu X. NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis. J Cancer 2018; 9(13):2374-2379. doi:10.7150/jca.26359. Available from http://www.jcancer.org/v09p2374.htm

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Notch family plays vital role in carcinogenesis and progression of various cancer, however, its clinical significance and prognostic value in colorectal cancer isn't fully investigated. In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248). The transcriptional and protein levels of NOTCH4 were evaluated by RT-PCR and immunohistochemistry study, respectively. Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes. In the univariate analysis, NOTCH3 and NOTCH4 were significantly correlated with prognosis in TCGA and GSE39582 database, respectively (P<0.05). For NOTCH3 has been studied in CRC, we chosen NOTCH4 for further study. NOTCH4 mRNA was higher in liver metastases than their primary colorectal cancer or normal mucosa. Increased NOTCH4 levels significantly correlated with advanced N stage (P= 0.002), M stage (P= 0.002), lymphovascular invasion (P= 0.026), and CEA status (P= 0.030). Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression. Multivariate survival analysis demonstrated that NOTCH4 was an independent prognostic biomarker for both DFS (HR 7.848; 95% CI 3.777-16.308; P<0.001) and OS (HR 5.323; 95% CI 2.668-10.623; P<0.001).Collectively, NOTCH4 may play critical role in colorectal cancer progression and could serve as a novel biomarker to predict survival after colectomy.

Keywords: NOTCH4, Colorectal cancer, Prognosis