Characterization of a soluble B7-H3 (sB7-H3) spliced from the intron and analysis of sB7-H3 in the sera of patients with hepatocellular carcinoma

Weiwei Chen; Peixin Liu; Yedong Wang; Weimin Nie; Zhiwei Li; Wen Xu; Fengyi Li; Zhiping Zhou; Min Zhao; Henggui Liu

doi:10.1371/journal.pone.0076965

Characterization of a soluble B7-H3 (sB7-H3) spliced from the intron and analysis of sB7-H3 in the sera of patients with hepatocellular carcinoma

PLoS One. 2013 Oct 23;8(10):e76965. doi: 10.1371/journal.pone.0076965. eCollection 2013.

Authors

Weiwei Chen¹, Peixin Liu, Yedong Wang, Weimin Nie, Zhiwei Li, Wen Xu, Fengyi Li, Zhiping Zhou, Min Zhao, Henggui Liu

Affiliation

¹ State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, China ; Treatment and Research Center for Infectious Diseases, 302 Hospital of P.L.A., Beijing, China.

Abstract

B7-H3 is a recently discovered member of the B7 superfamily molecules and has been found to play a negative role in T cell responses. In this study, we identified a new B7-H3 isoform that is produced by alternative splicing from the forth intron of B7-H3 and encodes the sB7-H3 protein. Protein sequence analysis showed that sB7-H3 contains an additional four amino acids, encoded by the intron sequence, at the C-terminus compared to the ectodomain of 2Ig-B7-H3. We further found that this spliced sB7-H3 plays a negative regulatory role in T cell responses and serum sB7-H3 is higher in patients with hepatocellular carcinoma (HCC) than in healthy donors. Furthermore, we found that the expression of the spliced sb7-h3 gene is higher in carcinoma and peritumor tissues than in PBMCs of both healthy controls and patients, indicating that the high level of serum sB7-H3 in patients with HCC is caused by the increased expression of this newly discovered spliced sB7-H3 isoform in carcinoma and peritumor tissues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alternative Splicing / genetics
Amino Acid Sequence
B7 Antigens / blood
B7 Antigens / genetics*
B7 Antigens / immunology*
Base Sequence
Carcinoma, Hepatocellular / blood*
China
Cloning, Molecular
DNA Primers / genetics
Enzyme-Linked Immunosorbent Assay
Female
Humans
Inteins / genetics
Liver Neoplasms / blood*
Male
Molecular Sequence Data
Protein Isoforms / blood
Protein Isoforms / genetics
Real-Time Polymerase Chain Reaction
Sequence Analysis, DNA
T-Lymphocytes / immunology

Substances

B7 Antigens
CD276 protein, human
DNA Primers
Protein Isoforms

Grants and funding

This work was supported by the grants from State Key Laboratory of Veterinary Biotechnology Research Fund (SKLVBP201217), Chinese Special Fund for Agro-scientific Research in the Public Interest (201303033), the National Nature Science Foundation of China (81072423), and National Grand Program on Key Infectious Disease (2012ZX10005-006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.