Dong-Hao Wu1, Tian-Tian Wang1, Dan-Yun Ruan1, Xing Li2, Zhan-Hong Chen2, Jing-Yun Wen1, Qu Lin2, Xiao-Kun Ma2, Xiang-Yuan Wu3, Chang-Chang Jia4. 1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China. 2. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China. Electronic address: wuxiangy@mail.sysu.edu.cn. 4. Guangdong Provincial Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, China; Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: jarsweet@126.com.
Abstract
BACKGROUND: Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1's capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. METHODS: The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. RESULTS: The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P=0.035), high levels of serum AFP (P=0.049), more frequency of node metastasis (P=0.015), later TNM stage (P=0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P=0.021), while LC3B were suggested to be negatively related with patients' PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P=0.002) and shorter 5-year progression free survival (PFS)(P=0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. CONCLUSION: ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.
BACKGROUND: Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1's capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. METHODS: The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. RESULTS: The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P=0.035), high levels of serum AFP (P=0.049), more frequency of node metastasis (P=0.015), later TNM stage (P=0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P=0.021), while LC3B were suggested to be negatively related with patients' PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P=0.002) and shorter 5-year progression free survival (PFS)(P=0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. CONCLUSION:ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.
Authors: Michael C J Quinn; Karen McCue; Stuart MacGregor; Georgia Chenevix-Trench; Wei Shi; Sharon E Johnatty; Jonathan Beesley; Andrew Civitarese; Tracy A O'Mara; Dylan M Glubb; Jonathan P Tyrer; Sebastian M Armasu; Jue-Sheng Ong; Puya Gharahkhani; Yi Lu; Bo Gao; Ann-Marie Patch; Peter A Fasching; Matthias W Beckmann; Diether Lambrechts; Ignace Vergote; Digna R Velez Edwards; Alicia Beeghly-Fadiel; Javier Benitez; Maria J Garcia; Marc T Goodman; Thilo Dörk; Matthias Dürst; Francesmary Modugno; Kirsten Moysich; Andreas du Bois; Jacobus Pfisterer; Klaus Bauman; Beth Y Karlan; Jenny Lester; Julie M Cunningham; Melissa C Larson; Bryan M McCauley; Susanne K Kjaer; Allan Jensen; Claus K Hogdall; Estrid Hogdall; Joellen M Schildkraut; Marjorie J Riggan; Andrew Berchuck; Daniel W Cramer; Kathryn L Terry; Line Bjorge; Penelope M Webb; Michael Friedlander; Tanja Pejovic; Melissa Moffitt; Rosalind Glasspool; Taymaa May; Gabrielle E V Ene; David G Huntsman; Michelle Woo; Michael E Carney; Samantha Hinsley; Florian Heitz; Sian Fereday; Catherine J Kennedy; Stacey L Edwards; Stacey J Winham; Anna deFazio; Paul D P Pharoah; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-06-23 Impact factor: 4.090