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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

The association between ULK1 expression and NPC patients’ survival.Kaplan-Meier survival analysis of ULK1 expression for disease-specific survival in the validation cohort (A) and in the overall cases (B) (log-rank test).
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pone.0117375.g004: The association between ULK1 expression and NPC patients’ survival.Kaplan-Meier survival analysis of ULK1 expression for disease-specific survival in the validation cohort (A) and in the overall cases (B) (log-rank test).

Mentions: As shown in Fig. 4, Kaplan-Meier analysis showed that the DSS difference between subsets with high and low ULK1 expression was marginal in the validation and overall patients (P<0.001). To confirm the representativeness of the NPCs, we first tested well-established prognostic factors of patient survival. In the validation cohort, univariate analysis evaluated a significant impact of well-known clinical pathological prognostic parameters on patients’ survival, such as T status, overall clinical stage, as well as therapeutic response (P<0.05, Table 2). Assessment of patient survival also revealed that high expression of ULK1 was significantly correlated with poor DSS in the validation cohort (HR = 2.697, 95%CI (1.770–4.018); P<0.001, Table 2).


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 association between ULK1 expression and NPC patients’ survival.Kaplan-Meier survival analysis of ULK1 expression for disease-specific survival in the validation cohort (A) and in the overall cases (B) (log-rank test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117375.g004: The association between ULK1 expression and NPC patients’ survival.Kaplan-Meier survival analysis of ULK1 expression for disease-specific survival in the validation cohort (A) and in the overall cases (B) (log-rank test).
Mentions: As shown in Fig. 4, Kaplan-Meier analysis showed that the DSS difference between subsets with high and low ULK1 expression was marginal in the validation and overall patients (P<0.001). To confirm the representativeness of the NPCs, we first tested well-established prognostic factors of patient survival. In the validation cohort, univariate analysis evaluated a significant impact of well-known clinical pathological prognostic parameters on patients’ survival, such as T status, overall clinical stage, as well as therapeutic response (P<0.05, Table 2). Assessment of patient survival also revealed that high expression of ULK1 was significantly correlated with poor DSS in the validation cohort (HR = 2.697, 95%CI (1.770–4.018); P<0.001, Table 2).

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