Prognostic Significance of Simultaneous Measurement of Three Tumor Markers in Patients With Hepatocellular Carcinoma

Toyoda, Hidenori; Kumada, Takashi; Kiriyama, Seiki; Sone, Yoshitsugu; Tanikawa, Makoto; Hisanaga, Yasuhiro; Yamaguchi, Akihiro; Isogai, Masatoshi; Kikuchi, Yuji; Washizu, Junji

doi:10.1016/s1542-3565(05)00855-4

Cited by 98 publications

(97 citation statements)

References 28 publications

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“…9,10 AFP is associated with grade differentiation, 11 whereas PIVKA-II is related to vascular invasion. 12,13 However, these tumor markers have limited sensitivity and are less predictive than microvascular invasion, 14,15 which is the most potent determinant of recurrence and survival in HCC patients undergoing a hepatectomy. 5 Therefore, new biomarkers that are more strongly associated with prognosis and recurrence in HCC than AFP or PIVKA-II are highly desirable.…”

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confidence: 99%

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

et al. 2013

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The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 lL serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion. Conclusion: Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;57:2314-2325 H epatocellular carcinoma (HCC) is a common and fatal malignancy with a worldwide occurrence.1 Liver resection has shown the highest level of control among the local treatments for HCC and is associated with a good survival rate.2,3 However, the recurrence rates for HCC are still high even when a curative hepatectomy is performed. 4 Many factors associated with the prognosis and recurrence of HCC have now been reported. Vascular invasion of the portal vein and/or hepatic vein and tumor differentiation are important factors affecting survival and recurrence in HCC cases after a hepatectomy. 5,6 However, microvascular invasion and differentiation can only be detected by pathological examination just after a hepatectomy, and cannot be diagnosed preoperatively, and thus cannot be identified preoperatively either. Hence, the serum biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) are used as prognostic markers 7,8 and also as surrogate markers for microvascular invasion and tumor differentiation.9,10 AFP is associated with grade differentiation, 11 whereas PIVKA-II is related to vascularAbbreviations: AFP, alpha-fetoprotein; AFP-L3, lens cul...

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confidence: 99%

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

et al. 2013

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“…Sassa et al [27] reported that it was 44.3% for ≤ 2 cm. An assay that employs higher DCP diagnostic sensitivity has been introduced [25,26] , but the diagnostic sensitivity for small hepatocellular carcinoma still remains at about 50% [27][28][29][30] . Thus, most reports on biological properties of DCP positive hepatic carcinoma are based on more advanced diseases [7] .…”

Section: Discussionmentioning

confidence: 99%

“…However, the rate of detectable serum DCP levels in patients with small hepatocellular carcinoma is low [19][20][21][22][23][24] . Although methods have been improved [25,26] , sensitivity is still at about 50% for most small cell carcinoma [27][28][29][30] . Thus, almost all reports on the biological nature of DCP and its prognostic value are based on analyses of patients with larger or more advanced tumors with various degrees of hepatic functional reserve.…”

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confidence: 99%

Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

Hakamada

Kimura²,

Miura³

et al. 2008

WJG

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tumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body. INTRODUCTIONDes-gamma-carboxy prothrombin (DCP) is a tumor marker specific for hepatocellular carcinoma [1] . It is believed that the elevation of the serum DCP level correlates with the presence of vascular invasion or intrahepatic metastases [2][3][4][5][6][7][8] . Furthermore, DCP has been reported to be an independent prognostic factor for recurrence and survival after hepatic resection [4,[9][10][11][12][13] , liver transplantation [6,14] , ablation treatment [15][16][17] , and transarterial chemoembolization (TAE) treatment [18] . However, the rate of detectable serum DCP levels in patients with small hepatocellular carcinoma is low [19][20][21][22][23][24] . Although methods have been improved [25,26] , sensitivity is still at about 50% for most small cell carcinoma [27][28][29][30] . Thus, almost all reports on the biological nature of DCP and its prognostic value are based on analyses of patients with larger or more advanced tumors with various degrees of hepatic functional reserve. Reports on the relevance of preoperative DCP level as a prognostic marker in small hepatocellular carcinoma patients are rare.This study thus aimed analysing the predictive value of preoperative serum DCP level on tumor recurrence and prognosis, particularly in hepatocellular carcinoma patients who had undergone liver resection and who met the criteria for small hepatocellular carcinoma [31] , i.e. a single Abstract AIM: To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS:Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors. RESULTS:The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP ≥ 400 mAU/mL (P = 0.02) were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005). In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01). In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically. CONCLUSION:For small hepatocellular carcinoma, a high preoperative DCP level appears indicative for

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“…CEA measurement is mainly used to monitor colorectal carcinoma treatment, to identify recurrences after surgical resection, for staging or to localize cancer spread through measurement of biological fluids [2]. Alpha-feto protein (AFP) is a glycoprotein with a molecular mass of 70 kDa, which is synthesized in large quantities during embryonic development of the fetal yolk sac and liver, and it can be used as a marker for hepatocellular or germ cell (non-seminoma) carcinoma, except in pregnant individu als [3]. The carbohydrate antigen 125 (CA 125) is a glyco protein with about a 200 kDa molecular weight and is the most frequently used biomarker for ovarian cancer detection [4].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Four Tumor Markers (CEA, AFP, CA125 and CA19-9) on Sysmex HISCL- 5000 Immunoassay Analyzer

Bhatnagar¹

2015

Ann Clin Lab Res

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Background: Although great effort in standardization has been instituted worldwide, discrepancies among results from different immunoassay analyzers are still reported. Hence the evaluation of new assays has been advised before their implementation in the laboratory. We evaluated the assay performance of the Sysmex HISCL-5000 automated analyzer in measuring four tumor markers i.e. CEA, AFP, CA 125 and CA 19-9 and method comparison with ARCHITECT i2000SR immunoassay analyzer.

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Prognostic Significance of Simultaneous Measurement of Three Tumor Markers in Patients With Hepatocellular Carcinoma

Cited by 98 publications

References 28 publications

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

Evaluation of Four Tumor Markers (CEA, AFP, CA125 and CA19-9) on Sysmex HISCL- 5000 Immunoassay Analyzer

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