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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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Comparison of disease-specific survival based on a novel clinico-pathological prognostic model (including ULK1 expression, therapy response and overall clinical stage) in the validation cohort (A) and overall cases (B) (log-rank test).
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pone.0117375.g005: Comparison of disease-specific survival based on a novel clinico-pathological prognostic model (including ULK1 expression, therapy response and overall clinical stage) in the validation cohort (A) and overall cases (B) (log-rank test).

Mentions: Based on the results of multivariate survival analysis, we proposed a new clinico-pathological prognostic model composed of three variables: high ULK1 expression, advanced clinical stage and poor CRT response. Patients were categorized into three risk group: low-risk (0 risk factor), intermediate-risk (1 risk factor), and high risk (2–3 risk factors) groups. On Kaplan-Meier analysis, the 3 risk groups showed clear separation into 3 survival groups in the validation cohort (P<0.001, the specificity and sensitivity were 65.1% and 71.7%, Fig. 5A). Patients in the low- (n = 101), intermediate- (n = 74), and high- (n = 40) risk groups had a 5-year DSS of 80%, 61% and 15% respectively. For the overall cases, the new prognostic model also could differentiate different patients with different outcomes (5-year DSS of low- (n = 260), intermediate- (n = 197), and high- (n = 93) risk group was 83%, 45%, and 30% respectively) (P<0.001, the specificity and sensitivity were 70.1% and 77.2%, Fig. 5B).


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)

Comparison of disease-specific survival based on a novel clinico-pathological prognostic model (including ULK1 expression, therapy response and overall clinical stage) in the validation cohort (A) and overall cases (B) (log-rank test).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117375.g005: Comparison of disease-specific survival based on a novel clinico-pathological prognostic model (including ULK1 expression, therapy response and overall clinical stage) in the validation cohort (A) and overall cases (B) (log-rank test).
Mentions: Based on the results of multivariate survival analysis, we proposed a new clinico-pathological prognostic model composed of three variables: high ULK1 expression, advanced clinical stage and poor CRT response. Patients were categorized into three risk group: low-risk (0 risk factor), intermediate-risk (1 risk factor), and high risk (2–3 risk factors) groups. On Kaplan-Meier analysis, the 3 risk groups showed clear separation into 3 survival groups in the validation cohort (P<0.001, the specificity and sensitivity were 65.1% and 71.7%, Fig. 5A). Patients in the low- (n = 101), intermediate- (n = 74), and high- (n = 40) risk groups had a 5-year DSS of 80%, 61% and 15% respectively. For the overall cases, the new prognostic model also could differentiate different patients with different outcomes (5-year DSS of low- (n = 260), intermediate- (n = 197), and high- (n = 93) risk group was 83%, 45%, and 30% respectively) (P<0.001, the specificity and sensitivity were 70.1% and 77.2%, Fig. 5B).

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