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Hu L.,Anal Colorectal Surgery Institute | Chen H.-Y.,150th Hospital of PLA | Feng D.,Shanghai University | Qi C.-Y.,Anal Colorectal Surgery Institute | And 4 more authors.
Tumor Biology | Year: 2015

Dehydrogenase/reductase (SDR family) member 9 (DHRS9) is aberrantly expressed in colorectal cancer (CRC), but its prognostic value is unknown. The aim of the work was to investigate the prognostic significance of DHRS9 expression in CRC. We found that DHRS9 was frequently downregulated in CRC clinical samples at both the messenger RNA (mRNA) and protein levels. Decreased expression of DHRS9 was significantly correlated with increased lymph node metastasis (p = 0.032), advanced tumor–node–metastasis (TNM) stage (p = 0.021), increased disease recurrence (p = 0.001), and death (p = 0.014). Kaplan–Meier analysis indicated that low DHRS9 expression predicted poor disease-free survival (p = 0.003) and disease-specific survival (p = 0.021). Cox multivariate analysis revealed that reduced expression of DHRS9 was an independent unfavorable prognostic indicator for CRC. Furthermore, combination of DHRS9 with TNM stage was a more powerful predictor of poor prognosis than either of the two parameters alone. Our results suggest that decreased expression of DHRS9 correlates with tumor progression and may serve as a potential prognostic biomarker in CRC. © 2015 The Author(s) Source


Hu L.,Anal Colorectal Surgery Institute | Chen H.-Y.,150th Hospital of PLA | Cai J.,150th Hospital of PLA | Zhang Y.,Anal Colorectal Surgery Institute | And 5 more authors.
BMC Cancer | Year: 2015

Background: Aberrant expression of serine threonine tyrosine kinase 1 (STYK1) has been reported in several human malignancies including colorectal cancer (CRC). However, the prognostic significance of STYK1 expression in CRC remains unknown. Methods: STYK1 protein expression in paraffin-embedded CRC specimens was determined immunohistochemically. The correlation of STYK1 expression with clinicopathologic features was assessed in a cohort containing 353 patients with primary CRC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between STYK1 expression and patients' survival. Results: STYK1 expression was frequently up-regulated in CRC clinical samples at the protein levels and was significantly associated with tumor differentiation grade (p = 0.030), lymph node metastasis (p = 0.004), TNM stage (p = 0.007) and patient death (p < 0.001). Kaplan-Meier analysis indicated that patients with high intratumoral STYK1 expression had a significantly shorter disease-specific survival (DSS) than those with low expression (p < 0.001). Importantly, high levels of STYK1 protein predicted poor DSS for both stage II (p < 0.001) and stage III (p = 0.004) patients. Furthermore, multivariate analyses revealed that STYK1 protein expression was an independent prognostic indicator for both stage II (hazard ratio [HR], 2.472; p = 0.001) and stage III (HR, 2.001; p = 0.004) patients. Conclusions: Our results suggest that increased STYK1 protein expression correlates with disease progression and metastasis and may serve as a predictor of poor survival in CRC. © 2015 Hu et al.; licensee BioMed Central. Source


Hu L.,Anal Colorectal Surgery Institute | Chen H.-Y.,150th Hospital of PLA | Cai J.,150th Hospital of PLA | Feng D.,Shanghai University | And 7 more authors.
BMC Cancer | Year: 2015

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. © 2015 Hu et al. Source


Fan N.-J.,Anal Colorectal Surgery Institute | Gao C.-F.,Anal Colorectal Surgery Institute | Wang C.-S.,150th Hospital of PLA | Lv J.-J.,Anal Colorectal Surgery Institute | And 5 more authors.
Canadian Journal of Gastroenterology | Year: 2012

OBJECTIVE: To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach. METHODS: Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry. RESULTS: A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue. CONCLUSIONS: These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma. ©2012 Pulsus Group Inc. All rights reserved. Source


Yang G.-Z.,Anal Colorectal Surgery Institute | Hu L.,Anal Colorectal Surgery Institute | Cai J.,150th Hospital of PLA | Chen H.-Y.,150th Hospital of PLA | And 8 more authors.
BMC Cancer | Year: 2015

Background: Carbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers. Carbonic anhydrase VII (CA7), a member of the CA gene family, was recently demonstrated to be expressed in several human tissues including colon. Nevertheless, the expression and clinical relevance of CA7 in colorectal carcinoma (CRC) has not been investigated. Methods: Real-time PCR, western blot, and immunohistochemistry analyses were used to determine CA7 expression in CRC clinical samples. The correlation of CA7 expression with clinicopathologic features was assessed in 228 patients from Luoyang, China (training cohort) and validated in 151 patients from Shanghai, China (validation cohort). Kaplan-Meier and Cox proportional regression analyses were used to estimate the association between CA7 expression and patients' survival. Results: CA7 expression was frequently downregulated in CRC tissues at both the mRNA and protein levels. Reduced expression of CA7 was significantly correlated with poor differentiation, positive lymph node metastasis, advanced TNM stage and unfavorable clinical outcome not only in the training cohort but also in the validation set. Survival analysis indicated that patients with lower CA7 expression had a significantly shorter disease-specific survival (DSS) than those with higher CA7 expression. Importantly, further stage-based analyses revealed that decreased CA7 expression significantly predicted poor DSS and was an independent adverse prognostic indicator for patients with early stage tumors in both cohorts. Conclusions: Our results indicate that decreased expression of CA7 correlates with disease progression and predicts poor prognosis in CRC, especially for patients with early stage tumors. © 2015 Yang et al.; licensee BioMed Central. Source

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