Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma.

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. 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. 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. Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients.

Citation

Xiang-Nan Yu, Guang-Cong Zhang, Jia-Lei Sun, Hai-Rong Zhu, Xuan Shi, Guang-Qi Song, Shu-Qiang Weng, Ling Dong, Tao-Tao Liu, Xi-Zhong Shen, Hong-Ying Guo, Ji-Min Zhu. Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma. Annals of surgical oncology. 2020 May;27(5):1546-1557

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PMID: 32157528

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