Additional file 1: Table S1. of Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway

The clinicopathologic characteristics of the 112 GC patients who received surgery followed by adjuvant chemotherapy in this study. (DOC 40 kb

ULK1: A Promising Biomarker in Predicting Poor Prognosis and Therapeutic Response in Human Nasopharygeal Carcinoma

<div><p>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.</p></div

The predictive value of ULK1 expression regarding NPC patients’ treatment response.

<p>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).</p

The association of ULK1 expression with clinicopathological variables.

<p>a Mean age</p><p>b Chi-square test</p><p>RT, radiotherapy; CR, complete response; Non-CR (including PR, partial response; NC, no change; PD, progressive disease); IC, induction chemotherapy; RCT, radiochemotherapy</p><p>*Statistically significant difference</p><p>The association of ULK1 expression with clinicopathological variables.</p

Results of multivariate Cox proportional-hazards analysis for disease-specific survival for NPC patients.

<p>Cox propotional hazard regression model, enter; HR, Hazard ratio; CI, confidence interval; CR, complete response, Non-CR (including PR, partial response; NC, no change; PD, progressive disease)</p><p>*Statistically significant difference</p><p>Results of multivariate Cox proportional-hazards analysis for disease-specific survival for NPC patients.</p

Univariate analysis of ULK1 expression and various clinicopathological parameters in validation and overall cases of NPC patients.

<p>a Mean age.</p><p>Cox propotional hazard regression model, enter; HR, Hazard ratio; CI, confidence interval; CR, complete response, Non-CR (including PR, partial response; NC, no change; PD, progressive disease)</p><p>*Statistically significant difference</p><p>Univariate analysis of ULK1 expression and various clinicopathological parameters in validation and overall cases of NPC patients.</p

The association between ULK1 expression and NPC patients’ survival.

<p>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).</p

X-title plots of ULK1 expression for optimal cut-point selection in the training cohort.

<p>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).</p

The expression of ULK1 in NPC tissues.

<p>(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.</p

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).

<p>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).</p