The transcriptional profiling of glycogenes associated with hepatocellular carcinoma metastasis.

Tianhua Liu,Kai Jiang,Kun Guo,Jie Chen,Shu Zhang,Qinle Zhang,Yinkun Liu,Xin-Yuan Guan

doi:10.1371/journal.pone.0107941

Abstract

Background and objectiveMetastasis is one of the important reasons for the poor prognosis of hepatocellular carcinoma (HCC), abnormal glycosylation plays a pivotal role in HCC metastasis. The goal of this study was to screen and validate the transcriptional profiling of glycogenes associated with HCC metastasis.MethodologyThe differentially transcribed glycogenes were screened out by the Human Glycosylation RT2 Profiler PCR Array, and were identified by qRT-PCR in human HCC cell lines and their orthotopic xenograft tumors. Further analyses were performed with K-mean clustering, Gene Ontology (GO) and ingenuity pathways analysis (IPA). Four differentially transcribed glycogenes were validated in clinical cancer specimens by qRT-PCR.ResultsA total of thirty-three differentially transcribed glycogenes were obtained by comparison the transcription in the metastatic human HCC cell lines (MHCC97L, MHCC97H and HCCLM3) with the transcription in the non-metastatic HCC cell line Hep3B. Seven differentially transcribed glycogenes were selected to further identification in human HCC cell lines and their orthotopic xenograft tumors. According to their trends by K-mean clustering, all of the differentially transcribed glycogenes were classified in six clusters. GO analysis of the differentially transcribed glycogenes described them in biological process, subcellular location and molecular function. Furthermore, the partial regulatory network of the differentially transcribed glycogenes was acquired through the IPA. The transcription levels of galnt3, gcnt3, man1a1, mgat5b in non-metastatic and metastatic HCC clinical cancer specimens showed the same changing trends with the results in human HCC cell lines and their orthotopic xenograft tumors, and the divergent transcription levels of gcnt3 and mgat5b were statistically significant.ConclusionsThe transcriptional profiling of glycogenes associated with HCC metastasis was obtained and validated in this study and it might provide novel drug targets and potential biological markers for HCC metastasis.

Highlights

Hepatocellular carcinoma (HCC), which is the sixth common neoplasm, ranks the third in cancer mortality in the world [1]. 80% of the hepatocellular carcinoma (HCC) are mainly found in eastern Asia and subSaharan Africa [2]
A total of thirty-three differentially transcribed glycogenes were obtained by comparison the transcription in the metastatic human HCC cell lines (MHCC97L, MHCC97H and HCCLM3) with the transcription in the non-metastatic HCC cell line Hep3B
The transcriptional profiling of glycogenes associated with HCC metastasis was obtained and validated in this study and it might provide novel drug targets and potential biological markers for HCC metastasis

Summary

Introduction

Hepatocellular carcinoma (HCC), which is the sixth common neoplasm, ranks the third in cancer mortality in the world [1]. 80% of the HCC are mainly found in eastern Asia and subSaharan Africa [2]. Hepatocellular carcinoma (HCC), which is the sixth common neoplasm, ranks the third in cancer mortality in the world [1]. HCC is a complex process mediated by multiple genes. One reason for the high mortality can in part be attributed to extrahepatic metastasis [4] and the bottleneck in treatment of HCC is to prevent extrahepatic metastasis. The understanding of the gene transcription profiling underlying HCC metastasis will provide us new theoretical basis for HCC diagnosis and treatment. Metastasis is one of the important reasons for the poor prognosis of hepatocellular carcinoma (HCC), abnormal glycosylation plays a pivotal role in HCC metastasis. The goal of this study was to screen and validate the transcriptional profiling of glycogenes associated with HCC metastasis

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Conclusion