Heat-shock protein 27: A potential biomarker for hepatocellular carcinoma identified by serum proteome analysis

Feng, Ju-Tao; Liu, Yinkun; Song, Haiyan; Dai, Zhi; Qin, Lun–Xiu; Almofti, Mohamad Radwan; Fang, Changming; Lu, Haojie; Yang, Pengyuan; Tang, Zhao–You

doi:10.1002/pmic.200401309

Cited by 179 publications

(133 citation statements)

References 34 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: 73%

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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: 73%

“…In addition, by comparing these results with the most relevant study (12), the alteration of haptoglobin coincided with the previous studies. In our study, in conjunction with Western blot results and measurement of serum haptoglobin, we found that serum HP concentrations were increased in patients with HCC.…”

Section: Discussionsupporting

confidence: 65%

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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“…Several new HCC tumor markers have recently been clinically evaluated and found to be useful in HCC diagnosis, especially AFP-L3 and DCP [29,[32][33][34][35][36] as well as possibly hsp27, osteopontin, and glypican 3 [37][38][39][40][41]. The rapidly evolving fields of genomics and proteomics are now finding HCC-associated gene products that will likely find future usefulness in further defining HCC prognostic subsets [42][43][44], including metastasis potential [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study

2009

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Objectives 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. Results We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. Conclusion The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

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“…Western blotting was performed as described previously (9). Briefly, the protein concentrations was firstly measured using the Bradford assay, and 20 µg protein/lane was resolved on 12.5% SDS-PAGE.…”

Section: In-gel Tryptic Digestion and Maldi-tof Msmentioning

confidence: 99%

“…The silver stained gels were scanned, and resulting images were analyzed using the ImageMaster™ 2D Platinum Software (Version 5.0, Amersham Bioscience, Swiss Institute of Bioinformatics, Geneva, Switzerland) for spot detection, quantification, as well as comparative analyses, as described previously (9). Triplicates of 2-DE gels from each sample were produced to minimize run-to-run variation.…”

Section: Removal Of High Abundance Proteins From Serum Samplesmentioning

confidence: 99%

Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer

Tan

Ma²,

Wang³

et al. 2011

Oncol Rep

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Abstract. Gallbladder cancer is the most common malignant tumor of the biliary tract. Early diagnosis of gallbladder cancer is difficult because of the latent onset and lack of good biomarkers. To identify new biomarkers that improve the early diagnosis and/or serve as possible therapeutic targets in gallbladder cancer is essential. In the present study, serum proteins were separated by two-dimensional gel electrophoresis (2-DE) in 3 patients with gallbladder cancer and 3 healthy volunteers. The differentially expressed spots were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Western blotting and immunohistochemistry were performed to verify the expression of certain candidate proteins. Protein expression and clinical correlation was evaluated. We found that 64 protein spots were significantly changed in gallbladder cancer. Twenty-four proteins including S100A10, haptoglobin, cystatin-B, profilin-1 and superoxide dismutase were successfully identified. Among these proteins, S100A10 and haptoglobin were validated using Western blotting. Immunohistochemically, the expression of S100A10 and haptoglobin proteins was found to be higher in gallbladder cancer tissues compared to that in gallbladder adenoma, liver cholangiocarcinoma and cholecystitis tissue. Patients with high expression of S100A10 and haptoglobin were linked to late stage disease and poor clinical prognosis. Our data suggest that combined comparative proteomic analysis by 2-DE and MALDI-TOF-MS is an effective method for identifying differentially expressed proteins in serum samples. These proteomic approaches could be used for identifying new serum biomarkers in gallbladder cancer. S100A10, haptoglobin and other identified proteins may be potential molecular targets for early gallbladder cancer diagnostics and therapeutic applications.

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Heat-shock protein 27: A potential biomarker for hepatocellular carcinoma identified by serum proteome analysis

Cited by 179 publications

References 34 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

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study

Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer

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