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NDRG4, a novel candidate tumor suppressor, is a predictor of overall survival of colorectal cancer patients.

Chu D, Zhang Z, Zhou Y, Li Y, Zhu S, Zhang J, Zhao Q, Ji G, Wang W, Zheng J - Oncotarget (2015)

Bottom Line: Significant negative correlations were found between NDRG4 staining and p-AKT.In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival.It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT
The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis. Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation. These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves of patients in the prospective study cohort(A) Correlation of NDRG4 staining with overall survival. (B) Correlation of p-AKT staining with overall survival among patients with tumors with positive NDRG4 staining. (C) Correlation of p-AKT staining with overall survival among patients with tumors with negative NDRG4 staining. (D) Survival curves for patients with aberrant NDRG4 and p-AKT coexpression.
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Figure 3: Kaplan-Meier survival curves of patients in the prospective study cohort(A) Correlation of NDRG4 staining with overall survival. (B) Correlation of p-AKT staining with overall survival among patients with tumors with positive NDRG4 staining. (C) Correlation of p-AKT staining with overall survival among patients with tumors with negative NDRG4 staining. (D) Survival curves for patients with aberrant NDRG4 and p-AKT coexpression.

Mentions: Kaplan-Meier analysis and log-rank test found that NDRG4 negative staining was significantly associated with poor overall survival of patients (Figure 3A), with an unadjusted HR of 2.05 (95% CI: 1.12–4.35; P < 0.001). This finding further strengthened the role of NDRG4 as a prognostic marker in colorectal cancer. With respect to clinicopathological characteristics, differentiation status, vascular invasion, lymph node metastasis and TNM stage were also associated with prognosis, which was similar to results in retrospective cohort indicating the homogeneity of the two study cohorts (Table 3). Univariate Cox regression analysis was performed accordting to retrospective study to assess whether NDRG4 was an independent prognostic predictor of survival. Results proved that negative NDRG4 staining was a significant independent predictor of poor survival, with an adjusted HR for of 2.13 (95% CI: 1.16–4.53; P < 0.001). These results were consistent with that in retrospective cohort study (Table 3).


NDRG4, a novel candidate tumor suppressor, is a predictor of overall survival of colorectal cancer patients.

Chu D, Zhang Z, Zhou Y, Li Y, Zhu S, Zhang J, Zhao Q, Ji G, Wang W, Zheng J - Oncotarget (2015)

Kaplan-Meier survival curves of patients in the prospective study cohort(A) Correlation of NDRG4 staining with overall survival. (B) Correlation of p-AKT staining with overall survival among patients with tumors with positive NDRG4 staining. (C) Correlation of p-AKT staining with overall survival among patients with tumors with negative NDRG4 staining. (D) Survival curves for patients with aberrant NDRG4 and p-AKT coexpression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480701&req=5

Figure 3: Kaplan-Meier survival curves of patients in the prospective study cohort(A) Correlation of NDRG4 staining with overall survival. (B) Correlation of p-AKT staining with overall survival among patients with tumors with positive NDRG4 staining. (C) Correlation of p-AKT staining with overall survival among patients with tumors with negative NDRG4 staining. (D) Survival curves for patients with aberrant NDRG4 and p-AKT coexpression.
Mentions: Kaplan-Meier analysis and log-rank test found that NDRG4 negative staining was significantly associated with poor overall survival of patients (Figure 3A), with an unadjusted HR of 2.05 (95% CI: 1.12–4.35; P < 0.001). This finding further strengthened the role of NDRG4 as a prognostic marker in colorectal cancer. With respect to clinicopathological characteristics, differentiation status, vascular invasion, lymph node metastasis and TNM stage were also associated with prognosis, which was similar to results in retrospective cohort indicating the homogeneity of the two study cohorts (Table 3). Univariate Cox regression analysis was performed accordting to retrospective study to assess whether NDRG4 was an independent prognostic predictor of survival. Results proved that negative NDRG4 staining was a significant independent predictor of poor survival, with an adjusted HR for of 2.13 (95% CI: 1.16–4.53; P < 0.001). These results were consistent with that in retrospective cohort study (Table 3).

Bottom Line: Significant negative correlations were found between NDRG4 staining and p-AKT.In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival.It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT
The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis. Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation. These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.

No MeSH data available.


Related in: MedlinePlus