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ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

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.

SUBMITTER: Yun M

PROVIDER: S-EPMC4340914 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Yun Miao M Bai Hai-Yan HY Zhang Jia-Xing JX Rong Jian J Weng Hui-Wen HW Zheng Zhou-San ZS Xu Yi Y Tong Zhu-Ting ZT Huang Xiao-Xia XX Liao Yi-Ji YJ Mai Shi-Juan SJ Ye Sheng S Xie Dan D

PloS one 20150225 2

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 train ...[more]

PMID: 25714809

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Project description:Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with high morbidity and mortality. Identifying specific molecular markers that can predict HCC prognosis is extremely important. MELK has been reported to play key roles in several types of human cancers and predict poor prognosis. This study was aimed to explore the impact of MELK on HCC. Methods: A pan-cancer analysis of MELK was conducted by The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data. The prognosis of MELK in various cancers was analyzed in GEPIA. Then, a ceRNA network of MELK was constructed based on the comprehensive consideration of the expression analysis, the correlation analysis, and the survival analysis by R software. The correlation of MELK and immune cell infiltration was analyzed by TIMER and CIBERSORT. Then, the overall survival of differentially expressed immune cells was conducted. The correlation of MELK and immune checkpoints expression was analyzed by GEPIA. Results: MELK was overexpressed in 14 types of human cancers, and its expression was significantly higher than that in both unmatched and paired normal samples in HCC. Higher MELK expression was correlated with poorer survival and advanced clinical stage, topography (T) stage, and histological grade. The univariate and multivariate Cox regression analyses showed that MELK was an independent risk factor for poor prognosis in HCC. Then, we constructed a ceRNA network consisting of MELK, miR-101-3p, and two lncRNAs (SNHG1 and SNHG6) after evaluating the expression and impact on prognosis in HCC of these RNAs. TIMER and CIBERSORT databases indicated that MELK was correlated with various immune cells including B cells, CD8+ T cells, CD4+ T cells, macrophage, neutrophil, and dendritic cells in HCC. Of them, B cells, CD4+ T cells, macrophage, and neutrophil were related to the prognosis of HCC. In addition, MELK was significantly positively correlated with the immune checkpoint genes. Conclusions: MELK may be a novel potential biomarker for predicting prognosis and immunotherapy efficacy in patients with HCC. Our study may provide new molecular and therapeutic strategies for the treatment of HCC patients.

Dataset Information

ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Publications

ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

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