Overexpression of TONSL might be an independent unfavorable prognostic indicator in hepatocellular carcinoma.
BACKGROUND
TONSL has been suggested to function as an oncogene in lung, esophageal and cervical cancer. This study was aimed to identify the expression of TONSL and its role in hepatocellular carcinoma (HCC).


METHODS
By data mining in the Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, the expression profile of TONSL, its clinical significance, the potential mechanisms of its dysregulation and its underlying biological function in HCC were investigated.


RESULTS
TONSL was significantly upregulated in HCC tissues relative to normal liver tissues (P < 0.05). High TONSL expression was significantly correlated with advanced TNM stage, poorly differentiated tumors, vascular invasion, elevated serum alpha-fetoprotein expression and a worse prognosis (all P < 0.05). Multivariate analysis further confirmed that TONSL overexpression was an independent risk factor for poor overall survival (OS) and recurrence-free survival (RFS) in HCC (all P < 0.05). Additionally, 16% of HCC cases (n = 370) had TONSL DNA amplification. The total methylation level of TONSL was moderately and negatively correlated with its mRNA expression (P < 0.05). TONSL was predictively targeted by miR-133b, which was downregulated in HCC and negatively related to TONSL mRNA expression (all P < 0.05). Kaplan-Meier analyses demonstrated that low miR-133b expression was significantly associated with poor OS and RFS (all P < 0.05). Moreover, gene set enrichment analysis revealed that cases with TONSL overexpression were enriched in cell cycle regulation pathways (all P < 0.05).


CONCLUSIONS
TONSL holds promise for serving as a prognostic biomarker for HCC. DNA amplification, hypomethylation and miR-133b downregulation could be the mechanisms associated with TONSL upregulation in HCC. TONSL might function as an oncogene via cell cycle regulation pathways in HCC.
['Yu|Bin|B|', 'Ding|Youming|Y|', 'Liao|Xiaofeng|X|', 'Wang|Changhua|C|', 'Wang|Bin|B|', 'Chen|Xiaoyan|X|']
D014408:Biomarkers, Tumor D006528:Carcinoma, Hepatocellular D057225:Data Mining D066264:Datasets as Topic D006801:Humans D008113:Liver Neoplasms D035683:MicroRNAs D016328:NF-kappa B D011379:Prognosis D015854:Up-Regulation
TONSL Hepatocellular carcinoma Prognosis miR-133b