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Down-regulation of TROP-2 Predicts Poor Prognosis of Hepatocellular Carcinoma Patients.
Sin, Sarah T K; Li, Yan; Liu, Ming; Yuan, Yun-Fei; Ma, Stephanie; Guan, Xin-Yuan.
Afiliação
  • Sin STK; Department of Clinical Oncology, Li Ka Shing Faculty of Medicine the University of Hong Kong Hong Kong.
  • Li Y; State Key Laboratory for Liver Research, Li Ka Shing Faculty of Medicine the University of Hong Kong Hong Kong.
  • Liu M; Department of Biology South University of Science and Technology of China Shenzhen China.
  • Yuan YF; School of Basic Sciences Guangzhou Medical University Guangzhou China.
  • Ma S; State Key Laboratory of Oncology in South China Sun Yat-Sen University Cancer Center Guangzhou China.
  • Guan XY; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine the University of Hong Kong Hong Kong.
Hepatol Commun ; 2(11): 1408-1414, 2018 Nov.
Article em En | MEDLINE | ID: mdl-30411086
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancer types worldwide, especially in Asian countries. Genetic alterations, including hyperactivation of oncogenes and loss of expression of tumor suppressor genes, greatly contribute to the initiation and progression of HCC. Here we report that down-regulation of trophoblast cell surface antigen 2 (TROP-2) was frequently detected in HCC. Transcriptome sequencing of non-tumor and HCC patient samples revealed down-regulation of TROP-2 in tumor tissues. Immunohistochemical staining showed nearly undetectable levels of TROP-2 in HCC tissues but distinct and strong staining of TROP-2 in adjacent non-tumor tissues. The frequent down-regulation of TROP-2 expression was further confirmed in an in-house cohort of 205 pairs of HCC patient samples and in the Cancer Genome Atlas (TCGA) databases. Furthermore, the down-regulation of TROP-2 was associated with poor overall survival of HCC patients, severe adjacent organ invasion, and poor differentiation of HCC. Using bisulfite genomic sequencing and methylation-specific polymerase chain reaction analyses, we show that higher levels of promoter methylation were detected in the DNA samples of HCC tissues (low TROP-2 expression) than that of the non-tumor tissues (high TROP-2 expression). Conclusion: Taken together, our data suggest that promoter hypermethylation contributes to the frequent down-regulation of TROP-2 in HCC, and that TROP-2 down-regulation predicts poor prognosis of HCC patients.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2018 Tipo de documento: Article