DNA topoisomerase IIα and Ki67 are prognostic factors in patients with hepatocellular carcinoma

Cao, Yi; Ke, Ruisheng; Shao-hu, Wang; Zhu, Xu; Chen, Jianwei; Huang, Chao; Jiang, Yi; Liu, Lizhi

doi:10.3892/ol.2017.5999

Cited by 30 publications

(36 citation statements)

References 33 publications

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“…Cell proliferation status is an important factor that reflects tumor biology and affects prognosis and treatment efficacy (5). Ki-67 protein, which is present in all phases of cell cycle (G 1 , S, G 2 and mitosis) except for resting cells (G 0 ), is an established marker suggestive of active cell proliferation (6).…”

Section: Introductionmentioning

confidence: 99%

Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study

Zheng

Jiang

Chen

et al. 2019

Chinese Journal of Cancer Research

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ObjectiveTo investigate the value of whole-lesion texture analysis on preoperative gadoxetic acid enhanced magnetic resonance imaging (MRI) for predicting tumor Ki-67 status after curative resection in patients with hepatocellular carcinoma (HCC).MethodsThis study consisted of 89 consecutive patients with surgically confirmed HCC. Texture features were extracted from multiparametric MRI based on whole-lesion regions of interest. The Ki-67 status was immunohistochemical determined and classified into low Ki-67 (labeling index ≤15%) and high Ki-67 (labeling index >15%) groups. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were applied for generating the texture signature, clinical nomogram and combined nomogram. The discrimination power, calibration and clinical usefulness of the three models were evaluated accordingly. Recurrence-free survival (RFS) rates after curative hepatectomy were also compared between groups.ResultsA total of 13 texture features were selected to construct a texture signature for predicting Ki-67 status in HCC patients (C-index: 0.878, 95% confidence interval: 0.791−0.937). After incorporating texture signature to the clinical nomogram which included significant clinical variates (AFP, BCLC-stage, capsule integrity, tumor margin, enhancing capsule), the combined nomogram showed higher discrimination ability (C-index: 0.936vs. 0.795, P<0.001), good calibration (P>0.05 in Hosmer-Lemeshow test) and higher clinical usefulness by decision curve analysis. RFS rate was significantly lower in the high Ki-67 group compared with the low Ki-67 group after curative surgery (63.27%vs. 85.00%, P<0.05). ConclusionsTexture analysis on gadoxetic acid enhanced MRI can serve as a noninvasive approach to preoperatively predict Ki-67 status of HCC after curative resection. The combination of texture signature and clinical factors demonstrated the potential to further improve the prediction performance.

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Section: Introductionmentioning

confidence: 99%

Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study

Zheng

Jiang

Chen

et al. 2019

Chinese Journal of Cancer Research

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“…Which was more importantly, the immunohistochemical results ( Fig 1C ) also showed that a negative correlation existed between SEPP1 and Ki67 expression. Since Ki67 was reported to be a traditional proliferation and differentiation index in numerous tumor [ 17 ], we demonstrated that the poor degree of differentiation, the lower expression of SEPP1. In addition, data (HTSeq-FRKM) from 374 of liver hepatocellular carcinoma (LIHC) cases and 50 of normal human were also obtained and analyzed by using the Cancer Genome Atlas Program (TCGA, https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga ) and R3.6.1.…”

Section: Resultsmentioning

confidence: 80%

Selenoprotein P inhibits cell proliferation and ROX production in HCC cells

et al. 2020

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Selenoprotein P (SEPP1) is a kind of secretory glycoproteins with an antioxidant effect during the development of some diseases. In this study, we attempted to observe the expression of SEPP1 in livers from the patients with hepatocellular carcinoma (HCC) and explore its effect on HCC cells. All the tissues from patients with HCC were obtained from Affiliated Hospital of Nantong University. Western blot and immunohistochemical results showed that SEPP1 was reduced in HCC liver tissues. Its expression was negatively correlated with Ki67 expression in tissues. The expression of SEPP1 in normal liver cell line was significantly higher than those in the liver cancer cell lines. Serum starvation and release experiment demonstrated that SEPP1 expression was reduced and PCNA expression was increased, when the serum was re-added into cell culture system and the cells were on a proliferation state. After SEPP1 over-expression plasmid was transfected into HepG2 cells, cell proliferation of HepG2 cells and PCNA expression level were all inhibited by SEPP1. Results obtained via 8-isoprostane ELISA further indicated that inhibited ROS level was found in HepG2 cells transfected with SEPP1 over-expression plasmid. In addition, RT-qPCR results demonstrated that GPX1 expression levels increased in HepG2 cells transfected with SEPP1 over-expression plasmid. In conclusion, SEPP1 may inhibit the proliferation of HCC cells, accompanied by the reduction of ROS production and the increasing of GPX1 expression.

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“…These patients were evaluated from the day of surgical resection to the last day of follow-up (August 15, 2017), with a median follow-up time of 59 months (range, 2.0–128.0 months). Liver function and tumor differentiation were assessed by Child-Pugh classification ( 18 ) and the Edmondson grading system ( 18 ), respectively. Tumor stages were assessed according to the 2010 International Union Against Cancer Tumor-Node-Metastasis (TNM) classification system ( 19 ), and curative resection was defined as previously described ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

“…Relapse-free survival (RFS) was defined as the interval between the date of surgery and the date of diagnosis of any type of relapse (intra-hepatic recurrence or extrahepatic metastasis). The inclusion criteria included the following: ECOG score ( 18 ) of 0–1 prior to surgery, absence of ascites, hepatic encephalopathy and any distant metastasis, only one tumor lesion and Child-Pugh class A. Clinicopathological data of the patients with HCC ( Table I ) were collected from the hospital database medical records. Survival information was obtained from medical records, telephone interviews and the Social Security Death Index ( 18 ), and all pathological data were pathological characteristics originally assessed by pathologists.…”

Section: Methodsmentioning

confidence: 99%

Prognostic value of heterogeneous ribonucleoprotein A1 expression and inflammatory indicators for patients with surgically resected hepatocellular carcinoma: Perspectives from a high occurrence area of hepatocellular carcinoma in China

Liu

Li³

et al. 2018

Oncol Lett

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Heterogeneous ribonucleoproteinA1 (hnRNPA1) is a documented tumor biomarker known to be aberrantly expressed in a number of types of human cancer. However, to the best of our knowledge, its prognostic value for surgically resected HCC (RHCC) in the high incidence areas of China has not been described; the association between hnRNPA1 expression, pre-operative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) is also not understood. In the present study, hnRNPA1 expression was retrospectively measured in two independent cohorts of patients with hepatocellular carcinoma (HCC) who underwent surgery to remove the primary cancer at one center in Fujian, an area with a high incidence of HCC in China. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry (IHC) were used to quantify hnRNPA1 expression in RHCC tissues. The survival curves were plotted using the Kaplan-Meier method, and the prognostic significance of hnRNPA1, NLR and PLR was analyzed using the log-rank test. The relevant prognostic factors were identified by multivariate Cox regression analysis. RT-qPCR and western blotting revealed that hnRNPA1 was upregulated in HCC tissues (P<0.001), and particularly overexpressed in tumor tissues of patients with recurrent HCC (P<0.001) (cohort 1; 54 patients). Differential hnRNPA1 expression was measured in 426HCC tissues with IHC; 259 exhibited high hnRNPA1 expression and 167 exhibited low expression. High hnRNPA1 expression was significantly associated with Tumor-Node-Metastasis stage (P=0.024), tumor size (P=0.027), vascular invasion (P<0.001), Edmonson grade (P<0.001), pre-operative serum α-fetoprotein (AFP) (P<0.001), NLR (P<0.001) and PLR (P<0.001). In addition, multivariate Cox regression analysis confirmed that high hnRNPA1 expression was associated with relapse-free survival (RFS; HR, 0.685; 95% CI, 0.506–0.928; P=0.015) and overall survival (OS; HR, 0.629; 95% CI, 0.454–0.871; P=0.005). Multivariate analysis confirmed that higher pre-operative serum AFP had an unfavorable impact on RFS (HR, 1.350; 95% CI, 1.006–1.811; P=0.045) and OS (HR=1.564; 95% CI, 1.151–2.126; P=0.004), while higher pre-operative NLR had an unfavorable impact on OS (HR, 1.758; 95% CI, 1.161–2.661; P=0.008) (cohort 2;426 patients). The expression of hnRNPA1 was also positively correlated with NLR (Spearman's correlation; r=0.122, P=0.012) and PLR (Spearman's correlation; r=0.140, P=0.004). In conclusion, high hnRNPA1 expression was revealed as prognostic for poor survival in patients with RHCC, and detection of hnRNPA1 protein in tumor tissues demonstrated potential in estimating survival for patients with RHCC in areas with high incidence rates. Furthermore, the combination of high hnRNPA1 expression and pre-operative serum AFP levels (>400 µg) proved to be a good diagnostic and prognostic biomarker for this specific population of patients. Finally, a correlation may also exist between hnRNPA1 expression and other markers of systemic inflammation.

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DNA topoisomerase IIα and Ki67 are prognostic factors in patients with hepatocellular carcinoma

Cited by 30 publications

References 33 publications

Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study

Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study

Selenoprotein P inhibits cell proliferation and ROX production in HCC cells

Prognostic value of heterogeneous ribonucleoprotein A1 expression and inflammatory indicators for patients with surgically resected hepatocellular carcinoma: Perspectives from a high occurrence area of hepatocellular carcinoma in China

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