Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma

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...

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Published in:Annals of surgical oncology 2020-05, Vol.27 (5), p.1546-1557
Main Authors: Yu, Xiang-Nan, Zhang, Guang-Cong, Sun, Jia-Lei, Zhu, Hai-Rong, Shi, Xuan, Song, Guang-Qi, Weng, Shu-Qiang, Dong, Ling, Liu, Tao-Tao, Shen, Xi-Zhong, Guo, Hong-Ying, Zhu, Ji-Min
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
AKT protein
Biomarkers, Tumor
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
Disease Progression
Disease-Free Survival
Female
Hepatocellular carcinoma
Humans
Kinases
Liver cancer
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
Medicine
Medicine & Public Health
Middle Aged
mTOR Associated Protein, LST8 Homolog - genetics
Multivariate Analysis
Nomograms
Oncology
Prognosis
Rapamycin
Surgery
Surgical Oncology
Therapeutic applications
TOR protein
Translational Research and Biomarkers
Up-Regulation
Young Adult
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Summary: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.
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-020-08263-6