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ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Yun M, Bai HY, Zhang JX, Rong J, Weng HW, Zheng ZS, Xu Y, Tong ZT, Huang XX, Liao YJ, Mai SJ, Ye S, Xie D - PLoS ONE (2015)

Bottom Line: High ULK1 expression was closely associated with aggressive clinical feature of NPC patients.Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group.These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

View Article: PubMed Central - PubMed

Affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China; Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.

ABSTRACT
Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

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The predictive value of ULK1 expression regarding NPC patients’ treatment response.Receiver operating characteristic curve analysis for ULK1 expression was performed to assess NPC treatment response in the training cohort (AUC = 0.643, P<0.001) (A) and in the validation cohort (AUC = 0.699, P<0.001) (B).
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pone.0117375.g003: The predictive value of ULK1 expression regarding NPC patients’ treatment response.Receiver operating characteristic curve analysis for ULK1 expression was performed to assess NPC treatment response in the training cohort (AUC = 0.643, P<0.001) (A) and in the validation cohort (AUC = 0.699, P<0.001) (B).

Mentions: We than applied the ROC curve analysis method to explore the predictive value of expression in therapeutic response in training and validation cohort. For ROC curve analysis, the treatment response was dichotomized: CR versus PR+NC+PD. The result showed a promising predictive value of regarding to treatment response in both training cohorts (AUC = 0.643, P<0.001) and validation cohort (AUC = 0.699, P<0.001) (Fig. 3).


ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Yun M, Bai HY, Zhang JX, Rong J, Weng HW, Zheng ZS, Xu Y, Tong ZT, Huang XX, Liao YJ, Mai SJ, Ye S, Xie D - PLoS ONE (2015)

The predictive value of ULK1 expression regarding NPC patients’ treatment response.Receiver operating characteristic curve analysis for ULK1 expression was performed to assess NPC treatment response in the training cohort (AUC = 0.643, P<0.001) (A) and in the validation cohort (AUC = 0.699, P<0.001) (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340914&req=5

pone.0117375.g003: The predictive value of ULK1 expression regarding NPC patients’ treatment response.Receiver operating characteristic curve analysis for ULK1 expression was performed to assess NPC treatment response in the training cohort (AUC = 0.643, P<0.001) (A) and in the validation cohort (AUC = 0.699, P<0.001) (B).
Mentions: We than applied the ROC curve analysis method to explore the predictive value of expression in therapeutic response in training and validation cohort. For ROC curve analysis, the treatment response was dichotomized: CR versus PR+NC+PD. The result showed a promising predictive value of regarding to treatment response in both training cohorts (AUC = 0.643, P<0.001) and validation cohort (AUC = 0.699, P<0.001) (Fig. 3).

Bottom Line: High ULK1 expression was closely associated with aggressive clinical feature of NPC patients.Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group.These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

View Article: PubMed Central - PubMed

Affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China; Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.

ABSTRACT
Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

Show MeSH
Related in: MedlinePlus