title: Upregulation of NETO2 expression correlates with tumor progression and poor prognosis in colorectal carcinoma.
abstract: BACKGROUND
  Neuropilin and tolloid-like 2 (NETO2) has been found to be overexpressed in different human cancers, but its expression pattern and clinical relevance in colorectal carcinoma (CRC) remains unknown.
  
  
  METHODS
  Real-time quantitative PCR, western blot and immunohistochemistry analyses were used to analyze the expression of NETO2 in CRC clinical samples. The correlation of NETO2 expression with clinicopathologic features was estimated in a cohort containing 292 patients with primary CRC. Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the prognostic value of NETO2 expression in CRC.
  
  
  RESULTS
  The expression of NETO2 was frequently upregulated in CRC clinical samples at both the mRNA and protein levels, and its upregulation was significantly correlated with poor tumor differentiation (p = 0.013), advanced local invasion (p = 0.049), increased lymph node metastasis (p = 0.009), advanced TNM stage (p = 0.041) and increased patient death (p = 0.001). Kaplan-Meier analysis of the complete study cohort revealed that patients with high-NETO2 tumors had a significantly shorter disease-specific survival (DSS) than those with low-NETO2 tumors (p < 0.001). Importantly, high levels of NETO2 protein predicted poor DSS for patients with early stage tumors (p = 0.027) and for those with advanced stage tumors (p = 0.020). Furthermore, multivariate analyses indicated that increased NETO2 expression was an independent unfavorable prognostic factor for patients with early stage tumors (hazard ratio [HR] = 1.937, 95% CI = 1.107-3.390, p = 0.021) as well as patients with advanced stage tumors (HR = 2.241, 95% CI = 1.245-4.035, p = 0.007).
  
  
  CONCLUSIONS
  Our findings suggest that NETO2 upregulation could serve as a potential biomarker for the prediction of advanced tumor progression and unfavorable prognosis in patients with CRC.
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. lianghudoc@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Oncology, 150th Hospital of PLA, Luoyang, China. chenocean@163.com.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery, 150th Hospital of PLA, Luoyang, China. jiancai150@yeah.net.
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Clinical Laboratory, 150th Hospital of PLA, Luoyang, China. guangzyang@163.com.
authors.forename: Guang-Zhen
authors.initials: GZ
authors.lastname: Yang
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China. fengdanlh@126.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. yanxiazai@163.com.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Zhai
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. hui_gong@yeah.net.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. chenye_qi@163.com.
authors.forename: Chen-Ye
authors.initials: CY
authors.lastname: Qi
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. yuzhang150@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. fuhao_150@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Gastrointestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. caiqingpingwcwk@163.com.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Cai
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China. chunfgao@163.com.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Gao
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C574595:NETO2 protein, human