Detection of fusion transcripts in the serum samples of patients with hepatocellular carcinoma

Yan-Ping Yu,George Michalopoulos,Jian-Hua Luo,Allan Tsung,Silvia Liu,Michael Nalesnick,David Geller

doi:10.18632/oncotarget.26918

Yan-Ping Yu, George Michalopoulos + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.26918

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Journal: Oncotarget	Publication Date: May 21, 2019
Citations: 22	License type: cc-by

Affiliation: University of Pittsburgh, The Ohio State University

Abstract

Hepatocellular carcinoma is one of the most lethal cancers in the United States. Early detection of the disease is crucial for reducing the mortality of this malignancy. Recently, we identified a panel of fusion genes present in several types of human cancers, including hepatocellular carcinoma. Among 8 fusion genes, MAN2A1-FER, TRMT11-GRIK2 and CCNH-C5orf30 appear most frequently in hepatocellular carcinoma samples. In this study, we showed that the fusion transcripts of MAN2A1-FER, CCNH-C5orf30 and SLC45A2-AMACR were detected in the serum samples of liver cancer patients as circulating cell-free RNA. The distributions of these gene fusion RNA fragments largely matched those of the primary HCC samples. In contrast, the sera of all healthy individuals free of human malignancies were shown to be negative for these fusion genes. These results suggest that gene fusion RNA is frequently shed from liver cancer cells. The detection of serum cell-free fusion transcripts may provide a new approach to aid in the diagnosis, follow-up or therapy of liver cancers.

Highlights

Human cancer is one of the most frequent causes of death in the United States
We identified a panel of fusion genes present in several types of human cancers, including hepatocellular carcinoma
We showed that the fusion transcripts of Mannosidase class 2 member A1 (MAN2A1)-Fez related tyrosine kinase (FER), CCNHC5orf30 and Solute carrier family 45 member 2 (SLC45A2)-Alpha-methylacylCoA racemase (AMACR) were detected in the serum samples of liver cancer patients as circulating cell-free RNA

Summary

Introduction

Human cancer is one of the most frequent causes of death in the United States. In 2018, the mortality rate of cancer reached 606,880 in the US [1], making cancer the second most lethal cause of death after cardiovascular diseases [2]. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, accounting for more than 31,000 deaths in the US alone [1]. The five-year survival rate for HCC is approximately 18%. Pancreatic adenocarcinoma and glioblastoma multiforme have lower survival rates [3]. The development of early detection methods and effective treatment for HCC is urgently needed to reduce the mortality of this disease.

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