Abstract
BackgroundEarly 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.MethodsSurgically 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.ResultsIn 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9130-0) contains supplementary material, which is available to authorized users.
Highlights
Recurrence after surgical resection is a hallmark of poor prognosis in hepatocellular carcinoma (HCC)
Samples were divided into four groups: primary tumor tissue from patients with HCC who showed recurrence within 2 years after surgery (Group S), tumor tissue from patients with HCC who did not show a relapse within 2 years after surgery (Group L), adjacent liver tissue from patients with HCC (Group A), and normal liver tissue from patients with colorectal cancer and liver metastasis (Group N)
We examined the survival of patients with HCC and confirmed that patients with early recurrence presented shorter survival than those without recurrence (Fig. 1)
Summary
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. Apoptosis is the major regulatory mechanism disturbed during carcinogenesis and cancer progression in HCC. Aberrant regulation of apoptosis-related proteins has been observed in more aggressive HCC cells. Anti-apoptotic regulators such as B cell lymphoma (Bcl)-2 family proteins have been identified as therapeutic targets in HCC [8, 9]. Apoptosis-associated receptors and ligands play key roles in HCC progression and are considered as therapeutic targets [11]. These observations strongly suggest that further investigation of the apoptosis pathway may reveal novel candidate biomarkers and therapeutic targets. The apoptosis pathway includes hundreds of proteins, only a limited number of proteins have been investigated in the context of HCC, and the clinical applicability of these proteins remained to be challenged
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