Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy

Yamamoto, Yusuke; Ikoma, Hisashi; Morimura, Ryo; Konishi, Hirotaka; Murayama, Yasutoshi; Komatsu, Shuhei; Shiozaki, Atsushi; Kuriu, Yoshiaki; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Fujiwara, Hitoshi; Okamoto, Kazuma; Sakakura, Chouhei; Ochiai, Toshiya; Otsuji, Eigo

doi:10.3748/wjg.v21.i4.1207

Cited by 83 publications

(82 citation statements)

References 34 publications

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“…However, these scores mostly rely on qualitative clinical parameters of the tumor characteristics such as age, symptoms and presurgery AFP which are only surrogate markers to tumor recurrence. 23 In our study, 102 out of the combined 106 tumors (96% of the tumors) satisfy this criterion. Furthermore, none of these clinical nomograms make any distinction between early and late recurrence of the tumor.…”

Section: Discussionmentioning

confidence: 62%

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Wang

Tan

Handoko

et al. 2019

Intl Journal of Cancer

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Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross‐referenced with RNA‐seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77‐gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER‐associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse‐transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence.

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Section: Discussionmentioning

confidence: 62%

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Wang

Tan

Handoko

et al. 2019

Intl Journal of Cancer

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“…The CDH17(+) HCC patients is expected to have tumor relapse within 9 months after the operation. For patients who were treated with curative hepatectomy, early recurrence was proved to be a poor prognostic factor for OS (21). In addition, CDH17 expression was associated with LNM and a likelihood of vascular invasion in HCC.…”

Section: Discussionmentioning

confidence: 98%

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19‑positive hepatocellular carcinoma

et al. 2017

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Abstract.A previous study demonstrated that cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) is an indicator of HCC invasiveness, including lymph node metastasis (LNM), tumor infiltration/non-encapsulation and poor prognosis. The exact mechanism by which CK19 expression results in poor prognosis remains unclear. Through the use of an Affymetrix U133A oligonucleotide microarray [20 patients with hepatitis B virus (HBV)-HCC], it was demonstrated that cadherin 17 (CDH17) significantly correlated with CK19 expression (R 2 , 0.867; P<0.001) in HBV-HCC. Immunohistochemical analysis (114 patients with HBV-HCC) also demonstrated a significant correlation between CK19 and CDH17 expressions in primary tumor tissue (R 2 , 0.414; P<0.001). In addition, CK19 and CDH17 expressions levels revealed a significant association with LNM (P<0.001). Cox regression multivariate analysis demonstrated that indocyanine green retention at 15 min >10% and CDH17 expression were independent prognostic factors for disease free survival (P=0.010 and 0.002, respectively). In vitro studies showed that epidermal growth factor can induce the expression of both CK19 and CDH17, and CDH17 in turn can enhance the expression of CK19 in HCC. In summary, this study demonstrated that the early recurrence and poor prognosis of CK19(+) HCC may be due to the expression of CDH17, a gene known to be associated with vascular invasion, tumor metastasis, and advanced tumor stage of HCC. Thus, novel therapeutics by targeting CDH17 may be beneficial for CK19(+) HCC.

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“…Another speculation is that sarcopenia might be an adverse consequence of liver cirrhosis, which results in an imbalance between protein synthesis and degradation [40]. Liver cirrhosis was found to be an independent factor of late recurrence, which is mainly caused by second primary lesions due to increased carcinogenicity of the affected liver [41]. Therefore, the link between skeletal muscle mass loss and tumor recurrence might be the byproduct of liver cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Chang¹,

Chen

Wu³

et al. 2017

Liver Cancer

142

140

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Background: Hepatocellular carcinoma (HCC) has multiple prognostic factors, and there is an increase in knowledge about the body composition and physical status of patients with HCC. The present meta-analysis aimed to explore whether loss of skeletal muscle mass is associated with mortality and tumor recurrence in patients with HCC. Method: A systematic search was conducted for published literature using PubMed, Embase, and Scopus. We included cohort or case-control studies investigating patients with HCC. The primary and secondary outcomes were the associations of loss of skeletal muscle mass with overall survival and tumor recurrence, respectively, expressed by a summary hazard ratio (HR) and 95% confidence interval (CI). Result: A total of 13 studies comprising 3,111 patients were included. The summary HRs calculated by either univariate or multivariate analysis both suggested a significant association between sarcopenia and all-cause mortality (crude HR = 2.04, 95% CI: 1.74-2.38; adjusted HR = 1.95, 95% CI: 1.60-2.37). Similarly, loss of skeletal muscle mass was associated with tumor recurrence (crude HR = 1.85, 95% CI: 1.44-2.37; adjusted HR = 1.76, 95% CI: 1.27-2.45). The stratified analysis showed that treatment types and inclusion of body mass index or body weight in the Cox regression model did not modify both clinical outcomes. With an increase in cut-off values of muscle mass on computed tomography images (especially for male patients), there was an insignificant trend of stronger associations between loss of skeletal muscle mass and all-cause mortality. Conclusion: Loss of skeletal muscle mass is associated with increased all-cause mortality and tumor recurrence in patients with HCC. Further prospective studies incorporating measurements of muscle strength and physical function are warranted to see whether inclusion of both parameters better predicts the outcome than use of muscle mass only.

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Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy

Abstract: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies.

Cited by 83 publications

References 34 publications

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19‑positive hepatocellular carcinoma

Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

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