Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT-LC-MS/MS

Kang, Xiaonan; Sun, Lu; Guo, Kun; Shu, Hong; Yao, Jun; Qin, Xue; Liu, Yinkun

doi:10.1007/s00432-010-0762-6

Cited by 43 publications

(33 citation statements)

References 23 publications

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“…Similar to previous reports (12,13), our study clearly shows the identified set of differentially overexpressed proteins, including serum amyloid A protein (SAA1), HP and sp40, between LC and HCC patients by 2-DE. They are all members of acute phase proteins (APPs) family, and most were responsible for liver-synthesized proteins.…”

Section: Discussionsupporting

confidence: 89%

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Diagnostic value of serum haptoglobin protein as hepatocellular carcinoma candidate marker complementary to α fetoprotein

Shu

Kang²,

Guo³

et al. 2010

Oncol Rep

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Abstract. More than 80% of hepatocellular carcinoma (HCC) arises in HBV based liver cirrhotic patients, suggesting that patients with cirrhosis form the main risk group of HCC. · fetoprotein (AFP) has poor sensitivity for the detection of AFP-negative and/or small tumors in HCC patients. Screening serum markers, along with HCC surveillance in patients with cirrhosis, can lead to the detection of HCC at an earlier stage, when curative therapy is likely to be more successful. Sera from 27 patients with HCC and 10 patients with HBV based liver cirrhosis (LC) were screened by comparative proteome analysis. Five significantly differential proteins (HP, Hp2, preprohaptoglobin, SP40 and SAA1) were identified using 2DE followed by MALDI-TOF-MS analysis. Haptoglobin (HP) was identified and found to be overexpressed in HCC as compared with LC. The result from Western blot analysis and turbidimetry detection showed serum levels of HP in HCC patients were significantly (p<0.05) higher than those in LC patients, which was consistent with the result of 2-DE. In addition, combining HP and AFP greatly improved the diagnostic accuracy (AUC=0.838). Additionally, serum HP also showed potential diagnostic value (AUC=0.763) for AFP-negative HCC patients. Altogether, it suggested that serum HP as a candidate marker complementary to · fetoprotein. IntroductionLiver cancer ranks second in China among all malignancies and its mortality is almost equal to its morbidity (1-3). Once diagnosed, it is at very late stage while conventional and effective treatment options become unavailable (4). More than 80% of HCCs arise in cirrhotic patients, suggesting that patients with cirrhosis form the main risk group of HCC (5). The screening biomarkers in high-risk populations such as cirrhotic patients have led to an early detection of small tumors amenable to resection and thus improve survival rates (4).An accurate, minimally invasive blood test could be routinely employed to screen for HCC. Serum ·-fetoprotein (AFP) is used widely for the detection and monitoring of HCC, however, the sensitivity and specificity of AFP varies from 40 to 65% and from 76 to 96%, respectively. Besides this, the AFP-negative rate for the patients with smaller HCCs was as high as 33.3% (6). Other HCC markers, such as des-Á-carboxy prothrombin, alkaline phosphatase isoenzyme-I (ALP-I), and tissue polypeptide specific antigen, have been utilized for differential diagnosis, however, their sensitivity and specificity are not high (7). Clearly, screening for new tumor biomarkers to improve HCC diagnosis is urgently needed.Comparative proteome as an emerging technology is a high-throughput approach to investigate cancer biomarkers and therapeutic targets (8,9). Two-dimensional gel electrophoresis (2-DE) combined with mass spectrometry (MS) is still a widely used and robust method for studying differential expression of proteins. In the present study, we used 2-DE based comparative proteome analysis to identify differentially expressed proteins between LC and HCC. The levels ...

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Section: Discussionsupporting

confidence: 89%

“…In this study, sera from 27 HCC patients with hepatocellular carcinoma (HCC) and 10 LC ONCOLOGY REPORTS 24: 1271-1276, 2010 …”

Section: Methodsmentioning

confidence: 99%

Diagnostic value of serum haptoglobin protein as hepatocellular carcinoma candidate marker complementary to α fetoprotein

Shu

Kang²,

Guo³

et al. 2010

Oncol Rep

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“…One such method uses isotope coded affinity tags (ICATs), involving chemical labeling of isolated proteins and peptides by isobaric tags that facilitates comparison of the proteomes of two samples simultaneously [40]. While ICATs involve chemical modification of proteins to tag them before analysis by mass spectrometry, stable isotope labeling with amino acids in cell culture (SILAC) is a simple approach for in vivo incorporation of a label (specific amino acids) into proteins that avoids chemical manipulations.…”

Section: Technologies Involved In Proteomicsmentioning

confidence: 99%

Serum-based protein biomarkers for detection of lung cancer

2014

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Lung cancer is one of the most common cancers in terms of both incidence and mortality.The major reasons for the increasing number of deaths from lung cancer are late detection and lack of effective therapies. To improve our understanding of lung cancer biology, there is urgent need for blood-based, non-invasive molecular tests to assist in its detection in a cost-effective manner at an early stage when curative interventions are still possible. Recent advances in proteomic technology have provided extensive, high throughput analytical tools for identification, characterization and functional studies of proteomes. Changes in protein expression patterns in response to stimuli can serve as indicators or biomarkers of biological and pathological processes as well as physiological and pharmacological responses to drug treatment, thus aiding in early diagnosis and prognosis of disease. However, only a few biomarkers have been approved by the FDA to date for screening and diagnostic purposes. This review provides a brief overview of currently available proteomic techniques, their applications and limitations and the current state of knowledge about important serum biomarkers in lung cancer and their potential value as prognostic and diagnostic tools.

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“…AAt belongs to acute phase protein (APP) whose expression is significantly increased in inflammation, trauma, infection and tumorigenesis. Many studies have suggested that serum levels of App have a high clinical value in various cancer diseases including colorectal cancer (20), lung cancer (21), hepatoma (22), breast cancer (23) and others (24). Protein level of serum AAT was significantly increased during inflammation trauma, infection, and tumorigenesis (20), especially in lung cancer (21) and liver cancer (25).…”

Section: Discussionmentioning

confidence: 99%

Screening for serological biomarkers of pancreatic cancer by two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry

Wang

Kuramitsu

Yoshino³

et al. 2011

Oncol Rep

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Abstract. pancreatic cancer (pc) is one of the most lethal malignant tumors because of late diagnosis and the lack of response to various therapies. to identify potential biomarkers in cancerous serum from early stage pc patients, we carried out two-dimensional gel electrophoresis (2-De) and liquid chromatography-tandem mass spectrometry (lc-Ms/Ms) to compare the serum proteomic profiles from 45 patients with pc and 20 healthy volunteers. seven spots showed differential expression on 2-De gels and two up-regulated protein spots were identified by lc-Ms/Ms as α-1-antitrypsin (AAt). These protein spots were also confirmed by Western blotting. This is the first time that AAT isoforms have been identified as potential serum biomarkers for pc. the serum isoforms of AAt may be clinically useful for pc diagnosis and monitoring.

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Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT-LC-MS/MS

Abstract: cICAT combined with LC-MS/MS-based serum proteome analysis can be useful in the screening of serum biomarkers for HCC. Alpha-1-acid glycoprotein combining AFP could aid the diagnosis of HCC.

Cited by 43 publications

References 23 publications

Diagnostic value of serum haptoglobin protein as hepatocellular carcinoma candidate marker complementary to α fetoprotein

Diagnostic value of serum haptoglobin protein as hepatocellular carcinoma candidate marker complementary to α fetoprotein

Serum-based protein biomarkers for detection of lung cancer

Screening for serological biomarkers of pancreatic cancer by two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry

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