Tumor Markers in Early Diagnosis, Follow-Up and Management of Patients with Hepatocellular Carcinoma

Fujiyama, Shigetoshi; Tanaka, Motohiko; Maeda, Seishi; Ashihara, Hiroshi; Hirata, Rika; Tomita, Kimio

doi:10.1159/000048277

Cited by 120 publications

(98 citation statements)

References 19 publications

(26 reference statements)

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“…30 On the other hand, it is well known that AFP may increase in some patients with acute and chronic hepatitis without HCC, 31,32 and that the elevation of AFP correlates with inflammation of background disease and hepatocyte regeneration. 33 Hence, because the AFP profile does not always directly reflect the extent of tumor malignancy, the AFP levels do not influence patient survival and recurrence. On the other hand, AFP and many important tumor markers, such as carcinoembryonic antigen, carbohydrate antigen 125, and carbohydrate antigen 19-9, are glycoproteins, and this means that the glycan profiles in serum are altered by the onset of cancer.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

et al. 2013

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“…Although sometimes Alpha-fetoprotein test displays the negative and false-positive results (Lok et al, 1989), the false diagnosis can be avoided through combination with other detection methods such as, imaging techniques or some other tumor markers testing (Fujiyama et al, 2002). Therefore, AFP is still a valuable marker for clinical assessment of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Xu¹,

Liu²,

Zhou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ≤20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alphafetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFPnegative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades Ⅲ/Ⅳ, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.

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“…Adenoviral vectors carrying CEA promoterdriven therapeutic genes were able to mediate targeted expression, tumor regression and prolonged survival in CEA + tumor-bearing mice [25], with minimal liver toxicity [26]. Because AFP and CEA are used as serum diagnostic markers in several carcinomas [27,28], employing these promoters as targets would be supported in expression-positive carcinomas.…”

Section: Transcriptional Targetingmentioning

confidence: 99%

Transcriptionally targeted gene therapy to detect and treat cancer

Wu¹,

Johnson²,

Sato³

2003

Trends in Molecular Medicine

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The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle that gene expression occurs at the correct location and at a sufficient level. Gene-based imaging can advance cancer detection and diagnosis. By combining the cancer-targeted imaging and therapeutic strategies, the exciting prospect of a 'one-two punch' to find hidden, disseminated cancer cells and destroy them simultaneously can potentially be realized.Multiple genetic alterations that confer growth advantages to tumor cells are accumulated during the transformation from normal to neoplastic growth [1]. The loss of growth suppressive genes or gain of oncogenes constitutes a common mechanism of oncogenesis. Based on this information, a rational therapeutic approach is to re-introduce the defective growth control genes into tumor cells. In addition, approaches of inducing apoptotic responses and enhancing anti-tumor immune responses have also been employed [2]. Due to the availability of multiple flexible therapeutic strategies, gene therapy is being actively investigated in clinical settings.Among the ~ 40 ongoing gene therapy clinical trials for cancer (searched via www.clinicaltrials.gov/), 18 of the trial protocols involve an immune activating scheme, ten studies employ a genetic correction strategy and five use a cytotoxic gene. With regard to genetic correction strategies, p53 is a major target. The recombinant adenovirus is the dominant viral gene delivery vector, and it is employed in 18 protocols. However, none of 40 protocols use a cancer-specific gene expression strategy. An oncolytic adenovirus CN706 containing prostate-specific antigen (PSA) promoter driven viral replication [3] is being evaluated in phase II clinical trial for prostate cancer [4].Because the goal of cancer gene therapy is to eradicate cancer cells, many therapeutic genes could be detrimental if unintentionally expressed in normal cells. Selectively targeting the cancer cells is useful to achieve safety and efficacy, especially when the gene therapy vector is directly delivered into patients. Based on features that distinguish cancerous from normal cells, three targeting strategies could be employed. Transcriptional targeting takes advantage of the fact that some cancer cells express a subset of exclusive genes, and uses these cancerspecific promoters to express the desired transgenes [5]. Transductional targeting refers to surface modification on the gene delivery vehicle to enhance interactions with the cancer cell membrane antigen, thereby improving gene transfer into the cancerous cell. A third promising approach is to exploit cancer-a...

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Tumor Markers in Early Diagnosis, Follow-Up and Management of Patients with Hepatocellular Carcinoma

Cited by 120 publications

References 19 publications

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Transcriptionally targeted gene therapy to detect and treat cancer

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