Preoperative Carbohydrate Antigen 19-9: Its Neglected Role in Alpha-Fetoprotein-Negative Hepatocellular Carcinoma Patients

Lü, Liang; Zhang, Yong Fa; Wei, Wei; Shi, Ming; Guo, Rong

doi:10.1007/s11605-017-3528-5

Cited by 14 publications

(10 citation statements)

References 36 publications

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“…Hepatic Resection. Hepatic resection was carried out as we have described previously [6,23]. To assess the number and size of the lesions and the relationship of the tumors to vascular structures, intraoperative ultrasonography was performed routinely.…”

Section: Preoperative Measurement Of the Serum Level Of Ggtmentioning

confidence: 99%

“…The prognosis of HCC patients remains unsatisfactory due to the extremely high incidence of recurrence after curative resection [2,3]. Currently, the universal blood biomarker used for the risk assessment and surveillance of HCC is serum α-fetoprotein (AFP), but nearly 30% of HCC patients have a normal serum level of AFP (AFP < 25 ng/mL) [4][5][6][7]. Data regarding the characteristics and outcomes of patients with tumors that do not produce AFP are limited.…”

Section: Introductionmentioning

confidence: 99%

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Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

Weiwei

Kan

et al. 2020

Disease Markers

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Background. Gamma-glutamyltransferase (GGT) is involved in tumor development and progression, but its prognostic value in α-fetoprotein- (AFP-) negative (AFP<25 ng/mL) hepatocellular carcinoma (HCC) patients remains unknown. Methods. A large cohort of 678 patients with AFP-negative HCC following curative resection who had complete data were enrolled in this study. The optimal cutoff value for the preoperative level of GGT was determined by the X-tile program. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were also identified. Results. The optimal cutoff values for the preoperative levels of GGT were 37.2 U/L and 102.8 U/L, which were used to divide all patients into three subgroups (group 1, GGT<37.2 U/L (n=211, 31.1%); group 2, GGT≥37.2 and <102.8 U/L (n=320, 47.2%); group 3, GGT≥102.8 U/L (n=147, 21.7%)), with distinct OS times (58.5 vs. 53.5 vs. 44.4 months, P<0.001) and DFS times (47.9 vs. 40.3 vs. 30.1 months, P<0.001). Elevated preoperative GGT levels were associated with an unfavorable tumor burden (larger tumor size, multiple tumors, and microvascular invasion) and were selected as independent predictors of a worse OS (group 2 vs. group 1, HR: 1.73 (1.13-2.65), P=0.011; group 3 vs. group 1, HR: 3.28 (2.10-5.13), P<0.001) and DFS (group 2 vs. group 1, HR: 1.52 (1.13-2.05), P=0.006; group 3 vs. group 1, HR: 2.11 (1.49-2.98), P<0.001) in multivariable analysis. Conclusions. Elevated preoperative GGT levels are associated with an unfavorable tumor burden and serve as an independent prognostic marker for worse outcomes in AFP-negative HCC patients following resection.

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Section: Preoperative Measurement Of the Serum Level Of Ggtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

Weiwei

Kan

et al. 2020

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“… 6 Only 33–65% of the tumors with a diameter of <3 cm in HCC patients had an elevated serum AFP level, 1 , 7 and nearly 30% of the patients had normal AFP levels. 8 , 9 Although AFP has its limitations as a biomarker for screening for liver cancer, it is still most widely used biomarker. Thus, it is crucial to identify new biomarkers for the diagnostic and prognostic evaluation of AFP-negative HCC and understand the underlying mechanisms of its tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Potential Molecular Biomarkers for Diagnosis and Prognosis of AFP-Negative HCC

Liu¹,

Pu²,

Bao³

et al. 2021

IJGM

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Background Alpha-fetoprotein (AFP) is the most important diagnostic and prognostic index of hepatocellular carcinoma (HCC). AFP-positive HCC can be easily diagnosed based on the serum AFP level and typical imaging features, but a number of HCC patients are negative (AFP < 20 ng/mL) for AFP. Therefore, it is necessary to develop novel diagnostic and prognostic biomarkers for AFP-negative HCC. Methods RNA data from TCGA and differential expression of lncRNAs, miRNAs, and mRNAs were downloaded to analyze the differential RNA expression patterns between AFP-negative HCC tissues and normal tissues. A lncRNA-miRNA-mRNA ceRNA regulatory network was constructed to elucidate the interaction mechanism of RNAs. Functional enrichment analysis of these DEmRNAs was performed to indirectly reveal the mechanism of action of lncRNAs. A PPI network was built using STRING, and the hub genes were identified with Cytoscape. The diagnostic value of hub genes was assessed with receiver operating characteristic (ROC) analysis. And the prognostic value of RNAs in the ceRNA was estimated with Kaplan–Meier curve analysis. Results A total of 131 lncRNAs, 185 miRNA, and 1309 mRNAs were found to be differentially expressed in AFP-negative HCC. A ceRNA network consisting of 12 lncRNA, 23 miRNA, and 74 mRNA was constructed. The top ten hub genes including EZH2, CCNB1, E2F1, PBK, CHAF1A, ESR1, RRM2, CCNE1, MCM4, and ATAD2 showed good diagnostic power under the ROC curve; and 2 lncRNAs (LINC00261, LINC00482), 3 miRNAs (hsa-miR-93, hsa-miR-221, hsa-miR-222), and 2 mRNAs (EGR2, LPCAT1) were found to be associated with the overall survival of AFP-negative patients. Conclusion This study could provide a novel insight into the molecular pathogenesis of AFP-negative HCC and reveal some candidate diagnostic and prognostic biomarkers for AFP-negative HCC.

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“…Zhang [ 10 ], Gan [ 11 ], and Wang et al [ 12 ] investigated the prognostic factors of AFP-negative HCC, but none of their studies included AFP as the prognostic factor. Besides, Blank [ 13 ] and Lu et al [ 14 ] reported the controversial prognostic effect of AFP. Blank et al reported that AFP was an independent prognostic factor for HBV-HCC patients underwent hepatectomy, and slight changes of AFP within the range of normality may affect prognosis of HBV-HCC; however, Lu et al failed to find the prognostic effect of AFP in their study.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Alpha-Fetoprotein in Alpha-Fetoprotein Negative Hepatocellular Carcinoma Underwent Curative Resection

et al. 2021

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Background The clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial. Aims To investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup. Methods A total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan–Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC). Results Even in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor ( P < 0.001), poorer differentiation of tumor cell ( P < 0.001), presence of satellite nodules ( P < 0.001), and MVI ( P = 0.002). Kaplan–Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS ( P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system. Conclusions AFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system. Supplementary Information The online version of this article (10.1007/s10620-020-06797-z) contains supplementary material, which is available to authorized users.

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Preoperative Carbohydrate Antigen 19-9: Its Neglected Role in Alpha-Fetoprotein-Negative Hepatocellular Carcinoma Patients

Abstract: Preoperative CA19-9 > 32.6 U/ml is a predictor of dismal prognosis and can be employed as a prognostic marker for patient selection in AFP-negative HCC management.

Cited by 14 publications

References 36 publications

Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

Investigation of Potential Molecular Biomarkers for Diagnosis and Prognosis of AFP-Negative HCC

Clinical Significance of Alpha-Fetoprotein in Alpha-Fetoprotein Negative Hepatocellular Carcinoma Underwent Curative Resection

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