PMID- 32157528 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210111 IS - 1534-4681 (Electronic) IS - 1068-9265 (Linking) VI - 27 IP - 5 DP - 2020 May TI - Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma. PG - 1546-1557 LID - 10.1245/s10434-020-08263-6 [doi] AB - BACKGROUND: The mechanistic target of rapamycin (mTOR) pathway, containing mTOR complex 1 (mTORC1) and mTORC2, is dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). Mammalian lethal with sec-13 protein 8 (mLST8) is a shared constituent of both mTORC1 and mTORC2, yet little is known regarding its role in HCC development. METHODS: mLST8 expression was detected in a total of 186 pairs of HCC and adjacent non-tumor specimens. The correlation between mLST8 level and clinicopathological features or prognostic significance were analyzed. The role of mLST8 on biological functions was also preliminarily studied. RESULTS: The study revealed that the mLST8 level was dramatically higher in HCC specimens than in adjacent non-tumor specimens. mLST8 overexpression positively correlated with tumor size, differentiation, and vessel invasion. Cases with elevated mLST8 level had more unfavorable overall survival (OS) and disease-free survival (DFS) than those with downregulated mLST8 level. Multivariate analysis demonstrated that mLST8 upregulation was an independent predictive marker for OS and DFS. Calibration curves from nomogram models indicated an excellent coherence between nomogram prediction and actual situation. Decision curve analysis proved that mLST8-based nomograms presented much higher predictive accuracy when compared with conventional clinical staging systems. Mechanistically, mLST8 enhanced cell proliferation and invasion through the AKT (protein kinase B) pathway. CONCLUSIONS: Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients. FAU - Yu, Xiang-Nan AU - Yu XN AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Zhang, Guang-Cong AU - Zhang GC AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Sun, Jia-Lei AU - Sun JL AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Zhu, Hai-Rong AU - Zhu HR AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Shi, Xuan AU - Shi X AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Song, Guang-Qi AU - Song GQ AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Weng, Shu-Qiang AU - Weng SQ AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Dong, Ling AU - Dong L AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Liu, Tao-Tao AU - Liu TT AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. FAU - Shen, Xi-Zhong AU - Shen XZ AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. AD - Shanghai Institute of Liver Disease, Shanghai, China. AD - Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Guo, Hong-Ying AU - Guo HY AD - Department of Severe Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. hyguo310@163.com. FAU - Zhu, Ji-Min AU - Zhu JM AUID- ORCID: 0000-0002-2150-473X AD - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. zhu.jimin@zs-hospital.sh.cn. AD - Shanghai Institute of Liver Disease, Shanghai, China. zhu.jimin@zs-hospital.sh.cn. LA - eng GR - 16ZR1406100/the Funding from Shanghai Science and Technology Commission/ GR - KY-GW-2018-18/a hospital-level project by Shanghai Public Health Clinical Center/ GR - 81472673/National Natural Science Foundation of China/ GR - 81672334/National Natural Science Foundation of China/ GR - 81672720/National Natural Science Foundation of China/ PT - Journal Article DEP - 20200310 PL - United States TA - Ann Surg Oncol JT - Annals of surgical oncology JID - 9420840 RN - 0 (Biomarkers, Tumor) RN - 0 (MLST8 protein, human) RN - 0 (mTOR Associated Protein, LST8 Homolog) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor MH - Carcinoma, Hepatocellular/*genetics/*pathology MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Humans MH - Liver Neoplasms/*genetics/*pathology MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Nomograms MH - Prognosis MH - Up-Regulation MH - Young Adult MH - mTOR Associated Protein, LST8 Homolog/*genetics EDAT- 2020/03/12 06:00 MHDA- 2021/01/12 06:00 CRDT- 2020/03/12 06:00 PHST- 2019/09/20 00:00 [received] PHST- 2020/03/12 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] PHST- 2020/03/12 06:00 [entrez] AID - 10.1245/s10434-020-08263-6 [pii] AID - 10.1245/s10434-020-08263-6 [doi] PST - ppublish SO - Ann Surg Oncol. 2020 May;27(5):1546-1557. doi: 10.1245/s10434-020-08263-6. Epub 2020 Mar 10.