SELDI-TOF MS Analysis of Hepatocellular Carcinoma in an Australian Cohort

Steven M Schlichtemeier; Christopher B Nahm; Aiqun Xue; Anthony J Gill; Ross C Smith; Thomas J Hugh

doi:10.1016/j.jss.2019.01.008

SELDI-TOF MS Analysis of Hepatocellular Carcinoma in an Australian Cohort

J Surg Res. 2019 Jun:238:127-136. doi: 10.1016/j.jss.2019.01.008. Epub 2019 Feb 13.

Authors

Steven M Schlichtemeier¹, Christopher B Nahm², Aiqun Xue³, Anthony J Gill⁴, Ross C Smith⁵, Thomas J Hugh⁶

Affiliations

¹ Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia. Electronic address: sschlich@gmp.usyd.edu.au.
² Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW, Australia; Discipline of Surgery, The University of Sydney, Camperdown, NSW, Australia.
³ Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia.
⁴ Department of Anatomical Pathology, Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney NSW and NSW Health Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
⁵ Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia; Discipline of Surgery, The University of Sydney, Camperdown, NSW, Australia.
⁶ Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW, Australia; Discipline of Surgery, The University of Sydney, Camperdown, NSW, Australia.

PMID: 30771682
DOI: 10.1016/j.jss.2019.01.008

Abstract

Background: Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Resection offers the best chance of long-term survival, but a consistent adverse prognostic factor is the presence of microvascular invasion (MVI). In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), a high throughput method of analyzing complex samples, was used to explore differentially expressed proteins between HCC and adjacent nontumour liver tissue (ANLT). These findings were correlated with clinical outcomes.

Materials and methods: From 2002 to 2011, tumor and ANLT were collected from patients who underwent liver resection and these samples were later prepared for SELDI-TOF MS. Output data were then used to identify proteins capable of discriminating HCC from ANLT. Proteins from the multivariate analysis were then analyzed to determine prognostic factors and the m/z ratios of these proteins were entered into the ExPASy database to infer potential candidates.

Results: During the study period, 30 patients had SELDI-TOF MS performed on their HCC and ANLT samples. On multivariate analysis, a panel of four proteins-m/z 5840, m/z 8921, m/z 9961, and m/z 25,872-discriminated HCC from ANLT with an area under the ROC curve of 0.954 (P < 0.001). On prognostic factor assessment, decreased m/z 9961 was significantly associated with the presence of MVI (P = 0.025) and shorter disease-free survival (P = 0.045) in our patients. A potential candidate for this protein was coxsackievirus and adenovirus receptor, isoform 3 (CAR 3/7), which helps maintain tight junction integrity.

Conclusions: Using SELDI TOF-MS, we identified a panel of four proteins with excellent discriminative capacity between HCC and ANLT. Of these, m/z 9961 was the only protein significantly associated with a known poor prognostic factor (presence of MVI) and survival (shorter disease-free survival). While loss of CAR 3/7 could lead to MVI, further research is warranted to validate the identity of protein m/z 9961.

Keywords: HCC; Hepatocellular carcinoma; Microvascular invasion; Proteomics; SELDI-TOF MS; m/z 9961.

Publication types

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

MeSH terms

Aged
Australia / epidemiology
Biomarkers, Tumor / analysis*
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology*
Carcinoma, Hepatocellular / surgery
Disease-Free Survival
Female
Hepatectomy
Humans
Liver / blood supply
Liver / pathology
Liver / surgery
Liver Neoplasms / mortality
Liver Neoplasms / pathology*
Liver Neoplasms / surgery
Male
Microvessels / pathology
Middle Aged
Neoplasm Invasiveness / diagnosis
Neoplasm Invasiveness / pathology
Prognosis
Prospective Studies
Proteomics / methods
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
Survival Analysis

Substances

Biomarkers, Tumor