Antibody-based proteomics to identify an apoptosis signature for early recurrence of hepatocellular carcinoma

Clinical Proteomics

Satoshi Nara¹  Minoru Esaki¹  Tadashi Kondo³  Nobuyoshi Hiraoka²  Takuji Okusaka⁷  Noriaki Morofuji⁴  Hidenori Ojima⁶  Kazuaki Shimada¹  Yoshiro Kishi⁵ 

[1] Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, JapanHepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, JapanHepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan;Pathology Division, National Cancer Center Research Institute, Tokyo, JapanPathology Division, National Cancer Center Research Institute, Tokyo, JapanPathology Division, National Cancer Center Research Institute, Tokyo, Japan;Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan;Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDepartment of Surgery, Kugayama Hospital, Tokyo, JapanDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDepartment of Surgery, Kugayama Hospital, Tokyo, JapanDepartment of Surgery, Kugayama Hospital, Tokyo, JapanDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, JapanDepartment of Surgery, Kugayama Hospital, Tokyo, Japan;Research and Development Division, Molecular and Biological Laboratories, Nagano, JapanResearch and Development Division, Molecular and Biological Laboratories, Nagano, JapanResearch and Development Division, Molecular and Biological Laboratories, Nagano, Japan;Pathology Division, National Cancer Center Research Institute, Tokyo, JapanDepartment of Pathology, School of Medicine, Keio University, Tokyo, JapanPathology Division, National Cancer Center Research Institute, Tokyo, JapanPathology Division, National Cancer Center Research Institute, Tokyo, JapanDepartment of Pathology, School of Medicine, Keio University, Tokyo, JapanDepartment of Pathology, School of Medicine, Keio University, Tokyo, JapanPathology Division, National Cancer Center Research Institute, Tokyo, JapanDepartment of Pathology, School of Medicine, Keio University, Tokyo, Japan;Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, JapanHepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, JapanHepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan

关键词: Antibody-based proteomics;    Apoptosis;    Biomarker;    Early recurrence;    Hepatocellular carcinoma;   

DOI  :  10.1186/s12014-016-9130-0

来源: Humana Press Inc

【 摘 要 】

Abstract

Background

Early recurrence after surgical resection is a hallmark of poor prognosis in hepatocellular carcinoma (HCC). To determine the proteomic background of early recurrence of HCC, we focused on apoptosis-related proteins.

Methods

Surgically resected tumor tissues were obtained from 80 patients, including HCC tumor tissues, non-tumor tissues, and normal liver tissues. These samples were grouped in the discovery and validation sample sets. The expression level of 192 apoptosis-related proteins was monitored using 247 commercially available antibodies and western blotting. The intensity of protein bands was compared between the tumor and non-tumor tissues as well as between the patients who had recurrence within 2 years after surgery and those who did not.

Results

In the first screening, we used pooled samples. The intensity of 53 protein bands detected by 37 unique antibodies was higher in tumor tissues compared with normal liver tissues, especially tumor tissues from patients who had recurrence within 2 years after surgery. In the second screening, we examined individual samples used to make the pooled samples. Among the selected bands and antibodies, the intensity of 18 protein bands detected by 11 antibodies was higher in tumor tissues compared with that in normal tissues, especially tumor tissues from the patients with early recurrence after surgery. For the third screening, we examined the samples from newly enrolled patients using these 11 antibodies. Eighteen protein bands detected by six antibodies were selected by using the same criteria. The corresponding antigens included ERK1, PKG, Apaf1, BclX, phosphorylated c-abl, and PIASx1/2.

Conclusions

We screened 192 apoptosis-related proteins using specific antibodies and western blotting. We identified 6 apoptosis-related proteins associated with carcinogenesis and early recurrence in HCC. The biological and clinical significance of the identified proteins are worth further investigation.

【 授权许可】

Unknown