The serum proteomics tracking of hepatocellular carcinoma early recurrence following radical resection

Purpose: There is still lacking of highly sensitive and speci fi c biomarkers for the prediction of hepatocellular carcinoma (HCC) early recurrence, which has hindered further improvement of the clinical outcomes. We aim to fi nd highly sensitive and speci fi c biomarkers for the prediction of HCC recurrence. Patients and methods: By using isobaric tags for relative and absolute quantitation (iTRAQ)-based multidimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) technique, we have quantitatively investigated and monitored the proteome alterations of a series of serum after radical resection during the follow-up of 4 HCC patients. Results: A total of 27 differentially abundant proteins (DAPs) in serum were identi fi ed to be closely associated with the early recurrence of HCC, and these DAPs were particularly concentrated within ERK1/2 and nuclear factor- κ beta signaling pathways, suggesting the dysregulation of these two pathways played an important role in the pathological process of HCC early recurrence. Further investigation of a cohort of patients con fi rmed that the high serum level of PGK1 was closely associated with HCC early recurrence and poor prognosis. In addition, the serum level of PGK1 could be complementary with AFP to further improve the sensitivity and speci fi city for predicting the relapse of HCC. Conclusion: PGK1 might be an independent factor for the recurrence of HCC. And the PGK1 could be complementary with AFP to further improve the sensitivity and speci fi city in prognostic prediction of HCC relapse.

[1]  Ping Chen,et al.  The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma , 2017, Scientific Reports.

[2]  W. Chapman,et al.  Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in an International Cohort , 2017, Annals of surgery.

[3]  H. Xie,et al.  PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process , 2017, International journal of molecular sciences.

[4]  T. Frankel,et al.  Recurrence of hepatocellular carcinoma at surgical incision site: case series and review of literature , 2017, Annals of the Royal College of Surgeons of England.

[5]  Ben C. Collins,et al.  Quantitative proteomics: challenges and opportunities in basic and applied research , 2017, Nature Protocols.

[6]  J. Rowe,et al.  Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis , 2017, Journal of carcinogenesis.

[7]  A. Braillon Recurrence in Early-Stage Hepatocellular Carcinoma: CpG Methylation and Smoking. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Jiayin Yang,et al.  Liver resection versus liver resection plus TACE for patients with hepatocellular carcinoma beyond Milan criteria. , 2017, The Journal of surgical research.

[9]  K. Wakayama,et al.  Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection , 2017, Journal of surgical oncology.

[10]  G. Raimondo,et al.  Does the margin width influence recurrence rate in liver surgery for hepatocellular carcinoma smaller than 5 cm? , 2017, European review for medical and pharmacological sciences.

[11]  Xiaolong Liu,et al.  Reveal the molecular signatures of hepatocellular carcinoma with different sizes by iTRAQ based quantitative proteomics. , 2017, Journal of proteomics.

[12]  K. Aldape,et al.  Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. , 2016, Molecular cell.

[13]  G. Goh,et al.  Changing epidemiology of hepatocellular carcinoma in Asia. , 2015, Best practice & research. Clinical gastroenterology.

[14]  Amit G Singal,et al.  Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  Rui Zhu,et al.  LC‐MS/MS‐based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma , 2015, Proteomics.

[16]  M. Schwartz,et al.  Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. , 2015, Annals of surgery.

[17]  D. Pang,et al.  Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer , 2015, British Journal of Cancer.

[18]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[19]  Wei Zhang,et al.  Arginase-1 is a more sensitive marker than HepPar-1 and AFP in differential diagnosis of hepatocellular carcinoma from nonhepatocellular carcinoma , 2015, Tumor Biology.

[20]  S. Reddy,et al.  Reactive oxygen species in inflammation and tissue injury. , 2014, Antioxidants & redox signaling.

[21]  Yin-kun Liu,et al.  High-throughput screening of tumor metastatic-related differential glycoprotein in hepatocellular carcinoma by iTRAQ combines lectin-related techniques , 2013, Medical Oncology.

[22]  M. Bantscheff,et al.  High-resolution enabled TMT 8-plexing. , 2012, Analytical chemistry.

[23]  Yan Li,et al.  FLNA and PGK1 are Two Potential Markers for Progression in Hepatocellular Carcinoma , 2011, Cellular Physiology and Biochemistry.

[24]  W. Chapman,et al.  Surgical treatment of hepatocellular carcinoma: expert consensus statement. , 2010, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[25]  H. Northoff,et al.  PGK1 a Potential Marker for Peritoneal Dissemination in Gastric Cancer , 2008, Cellular Physiology and Biochemistry.

[26]  K. Shirabe,et al.  Clinicopathological risk factors linked to recurrence pattern after curative hepatic resection for hepatocellular carcinoma--results of 152 resected cases. , 2007, Hepato-gastroenterology.

[27]  Ying Liang,et al.  Overexpression and elevated serum levels of phosphoglycerate kinase 1 in pancreatic ductal adenocarcinoma , 2006, Proteomics.

[28]  A. Tall,et al.  High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion* , 2001, The Journal of Biological Chemistry.

[29]  N. Fidge High density lipoprotein receptors, binding proteins, and ligands. , 1999, Journal of lipid research.

[30]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[31]  D. Goodlett,et al.  Mass Spectrometry-Based Serum Proteomics for Biomarker Discovery and Validation. , 2017, Methods in molecular biology.

[32]  Wu Xinhua Clinical values of combined hepatoma-specific α-fetoprotein (AFP) fraction and AFP-mRNA determination in diagnosis and differentiation of hepatocellular carcinoma , 2006 .