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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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Related in: MedlinePlus

X-title plots of ULK1 expression for optimal cut-point selection in the training cohort.Patients in the training cohort were randomly divided into equal training (A) and pretesting subsets (B). The cut-point for the training set (IHC score > 4, P<0.001) is demarcated by the circle (black with white border), which was then used as the point separating low ULK1 expression (blue) from high ULK1 expression (gray) in the expression frequency of the whole set (middle panel). The right panel presents the Kaplan-Meier curve for examining the survival of cohort subsets defined by ULK1 expression ⩽4(blue line) and >4 (gray line).
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pone.0117375.g002: X-title plots of ULK1 expression for optimal cut-point selection in the training cohort.Patients in the training cohort were randomly divided into equal training (A) and pretesting subsets (B). The cut-point for the training set (IHC score > 4, P<0.001) is demarcated by the circle (black with white border), which was then used as the point separating low ULK1 expression (blue) from high ULK1 expression (gray) in the expression frequency of the whole set (middle panel). The right panel presents the Kaplan-Meier curve for examining the survival of cohort subsets defined by ULK1 expression ⩽4(blue line) and >4 (gray line).

Mentions: To develop a reasonable cutoff score and avoid the problems of multiple cutpoint selection, the X-tile program was employed to determine cutoff score for ULK1 expression. According to the X-tile plots, we dichotomized the training cohort into low (IHC score ≤4) and high (IHC score >4) expression subgroups based on a cut-point of more than IHC score 4 for high ULK1 expression, which achieved high statistical significance (Fig. 2). In the training cohort, high expression of ULK1 was observed in 189/335 (56.4%) of NPC samples, and in 7/45 (15.6%) normal nasopharyngeal mucosal tissues (P<0.001); in the validation cohort, high expression of ULK1 was observed in 119/215 (55.3%) of NPC samples according this generated cut-off point.


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)

X-title plots of ULK1 expression for optimal cut-point selection in the training cohort.Patients in the training cohort were randomly divided into equal training (A) and pretesting subsets (B). The cut-point for the training set (IHC score > 4, P<0.001) is demarcated by the circle (black with white border), which was then used as the point separating low ULK1 expression (blue) from high ULK1 expression (gray) in the expression frequency of the whole set (middle panel). The right panel presents the Kaplan-Meier curve for examining the survival of cohort subsets defined by ULK1 expression ⩽4(blue line) and >4 (gray line).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117375.g002: X-title plots of ULK1 expression for optimal cut-point selection in the training cohort.Patients in the training cohort were randomly divided into equal training (A) and pretesting subsets (B). The cut-point for the training set (IHC score > 4, P<0.001) is demarcated by the circle (black with white border), which was then used as the point separating low ULK1 expression (blue) from high ULK1 expression (gray) in the expression frequency of the whole set (middle panel). The right panel presents the Kaplan-Meier curve for examining the survival of cohort subsets defined by ULK1 expression ⩽4(blue line) and >4 (gray line).
Mentions: To develop a reasonable cutoff score and avoid the problems of multiple cutpoint selection, the X-tile program was employed to determine cutoff score for ULK1 expression. According to the X-tile plots, we dichotomized the training cohort into low (IHC score ≤4) and high (IHC score >4) expression subgroups based on a cut-point of more than IHC score 4 for high ULK1 expression, which achieved high statistical significance (Fig. 2). In the training cohort, high expression of ULK1 was observed in 189/335 (56.4%) of NPC samples, and in 7/45 (15.6%) normal nasopharyngeal mucosal tissues (P<0.001); in the validation cohort, high expression of ULK1 was observed in 119/215 (55.3%) of NPC samples according this generated cut-off point.

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