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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 expression of ULK1 in NPC tissues.(A) Western blot analysis of ULK1 protein expression in 10 representative paired of NPC (T) and adjacent normal mucosa tissues (N). Equal loading of protein was determined by GAPDH. The number below indicated the expression level of ULK1 relative to GAPDH in each samples. (B) An NPC case demonstrated low expression of ULK1, in which negative immunohistochemistry staining was observed in all the NPC cells (upper panel ×200). (C) An NPC case showed moderate ULK1 staining (upper panel ×200). (D) Strong ULK1 IHC signaling was detected in the cytoplasm pattern of the NPC cancer cells (upper panel ×200). (E) Normal nasopharyngeal mucosa tissue showed negative expression of ULK1 protein (upper panel ×200). The lower panels indicated the higher magnification (× 400) from the area of the box in B., C., D. and E., respectively.
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pone.0117375.g001: The expression of ULK1 in NPC tissues.(A) Western blot analysis of ULK1 protein expression in 10 representative paired of NPC (T) and adjacent normal mucosa tissues (N). Equal loading of protein was determined by GAPDH. The number below indicated the expression level of ULK1 relative to GAPDH in each samples. (B) An NPC case demonstrated low expression of ULK1, in which negative immunohistochemistry staining was observed in all the NPC cells (upper panel ×200). (C) An NPC case showed moderate ULK1 staining (upper panel ×200). (D) Strong ULK1 IHC signaling was detected in the cytoplasm pattern of the NPC cancer cells (upper panel ×200). (E) Normal nasopharyngeal mucosa tissue showed negative expression of ULK1 protein (upper panel ×200). The lower panels indicated the higher magnification (× 400) from the area of the box in B., C., D. and E., respectively.

Mentions: The expression of ULK1 was examined in 10 paired of NPC and ANTs. Our western blotting analysis demonstrated that the 8 out of 10 (80.0%) NPC cases also exhibited up-regulated ULK1 expression in protein level as compared to that in ANTs (Fig. 1A). For IHC staining, the positive ULK1 protein immunoreactivity was mainly detected in the cytoplasm pattern of tumor cells (Fig. 1B-D). Immunoreactivity score of ULK1 protein ranged from 0 to 12. On the other hand, among the 50 non-malignant tissues, absent or weak immunoreactivity staining of ULK1 protein was detected (Fig. 1E). In addition, we collected pairs of distant metastasis as well as pairs of recurrent NPC to compare their expression level in comparison with the primary NPC respectively. As shown in S1 Fig., in both distant metastasis and recurrent NPC, the expression level of ULK1 was much higher (P<0.05).


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 expression of ULK1 in NPC tissues.(A) Western blot analysis of ULK1 protein expression in 10 representative paired of NPC (T) and adjacent normal mucosa tissues (N). Equal loading of protein was determined by GAPDH. The number below indicated the expression level of ULK1 relative to GAPDH in each samples. (B) An NPC case demonstrated low expression of ULK1, in which negative immunohistochemistry staining was observed in all the NPC cells (upper panel ×200). (C) An NPC case showed moderate ULK1 staining (upper panel ×200). (D) Strong ULK1 IHC signaling was detected in the cytoplasm pattern of the NPC cancer cells (upper panel ×200). (E) Normal nasopharyngeal mucosa tissue showed negative expression of ULK1 protein (upper panel ×200). The lower panels indicated the higher magnification (× 400) from the area of the box in B., C., D. and E., respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0117375.g001: The expression of ULK1 in NPC tissues.(A) Western blot analysis of ULK1 protein expression in 10 representative paired of NPC (T) and adjacent normal mucosa tissues (N). Equal loading of protein was determined by GAPDH. The number below indicated the expression level of ULK1 relative to GAPDH in each samples. (B) An NPC case demonstrated low expression of ULK1, in which negative immunohistochemistry staining was observed in all the NPC cells (upper panel ×200). (C) An NPC case showed moderate ULK1 staining (upper panel ×200). (D) Strong ULK1 IHC signaling was detected in the cytoplasm pattern of the NPC cancer cells (upper panel ×200). (E) Normal nasopharyngeal mucosa tissue showed negative expression of ULK1 protein (upper panel ×200). The lower panels indicated the higher magnification (× 400) from the area of the box in B., C., D. and E., respectively.
Mentions: The expression of ULK1 was examined in 10 paired of NPC and ANTs. Our western blotting analysis demonstrated that the 8 out of 10 (80.0%) NPC cases also exhibited up-regulated ULK1 expression in protein level as compared to that in ANTs (Fig. 1A). For IHC staining, the positive ULK1 protein immunoreactivity was mainly detected in the cytoplasm pattern of tumor cells (Fig. 1B-D). Immunoreactivity score of ULK1 protein ranged from 0 to 12. On the other hand, among the 50 non-malignant tissues, absent or weak immunoreactivity staining of ULK1 protein was detected (Fig. 1E). In addition, we collected pairs of distant metastasis as well as pairs of recurrent NPC to compare their expression level in comparison with the primary NPC respectively. As shown in S1 Fig., in both distant metastasis and recurrent NPC, the expression level of ULK1 was much higher (P<0.05).

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