Microvessel Density and Clinicopathologic Characteristics in Hepatocellular Carcinoma with and without Cirrhosis

Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their adjacent background non-neoplastic liver tissue. There was no statistical difference in MVD between HCC-C and HCC-NC. A higher value of MVD was seen in tumors of intermediate size (5–10 cm), high histologic grade, the presence of lymphvascular space invasion, and the underlying etiology of hepatitis C and alcoholic steatohepatitis. This data indicates that MVD may play an important role in liver carcinogenesis and neoplastic progression. The difference in clinical behavior between HCC-C and HCC-NC does not seem to be associated with differences in tumor MVD. Objective measurement of MVD using standardized computer software could potentially be used as a clinical marker to predict patients’ prognosis.

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Absence of CD66a expression is associated with high microvessel density and high histologic grade in hepatocellular carcinoma

The Kaohsiung Journal of Medical Sciences ◽

10.1016/j.kjms.2016.05.007 ◽

2016 ◽

Vol 32 (6) ◽

pp. 306-312 ◽

Cited By ~ 1

Author(s):

Chun-Chieh Wu ◽

Sheau-Fang Yang ◽

Wan-Tzu Chen ◽

Hung-Pei Tsai ◽

Chi-Wen Luo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Microvessel Density ◽

Histologic Grade ◽

High Histologic Grade

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Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study

10.21203/rs.2.24456/v2 ◽

2020 ◽

Author(s):

Hongzhi Liu ◽

Yuan Yang ◽

Chuanchun Chen ◽

Lei Wang ◽

Qizhen Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Proportional Hazards ◽

Univariate Analysis ◽

Prognostic Significance ◽

Cox Proportional Hazards ◽

P Value ◽

Clinicopathologic Characteristics ◽

B Virus ◽

The Difference

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary hepatitis B virus (HBV) related HCC.Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm interval. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). If multiple cutoffs meet the above standard, univariate analysis will be performed by using the Cox proportional hazards regression model, and hazard ratio (HR) will be considered as a criterion to assess the difference in survival.Results There are 8 dichotomy, 8 trichotomy and no inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. The HR values of tumor size at these trichotomy cutoffs for OS were compared, the highest HR value is 2.79 when size cutoff is 3/9cm. Then, we reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.

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A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy

BMC Cancer ◽

10.1186/s12885-021-07916-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dongdong Zhou ◽

Xiaoli Liu ◽

Xinhui Wang ◽

Fengna Yan ◽

Peng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Surgical Therapy ◽

Calibration Curve ◽

Cox Regression ◽

Validation Cohort ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Alpha Fetoprotein ◽

Clinicopathologic Characteristics

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.

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Baseline apparent diffusion coefficients: Validation study of new predictor of survival in patients with unresectable hepatocellular carcinoma following chemoembolization

Journal of X-Ray Science and Technology ◽

10.3233/xst-200827 ◽

2021 ◽

pp. 1-10

Author(s):

Lichao Xu ◽

Shiqin Wang ◽

Shengping Wang ◽

Ying Wang ◽

Wentao Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Roc Curve ◽

Cox Regression ◽

Response To Treatment ◽

Roc Curve Analysis ◽

Adc Value ◽

Apparent Diffusion Coefficients ◽

Apparent Diffusion ◽

Response Biomarker ◽

The Difference

OBJECTIVES: To investigate whether the baseline apparent diffusion coefficient (ADC) can predict survival in the hepatocellular carcinoma (HCC) patients receiving chemoembolization. MATERIALS AND METHODS: Diffusion-weighted MR imaging of HCC patients is performed within 2 weeks before chemoembolization. The ADC of the largest index lesion is recorded. Responses are assessed by mRECIST after the start of the second course of chemoembolization. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic performance and determine optimal cut-off values. Cox regression and Kaplan–Meier survival analyses are used to explore the differences in overall survival (OS) between the responders and non-responders. RESULTS: The difference is statistically significant in the baseline ADC between the responders and non-responders (P < 0.001). ROC analyses indicate that the baseline ADC value is a good predictor of response to treatment with an area under the ROC curve (AUC) of 0.744 and the optimal cut-off value of 1.22×10–3 mm2/s. The Cox regression model shows that the baseline ADC is an independent predictor of OS, with a 57.2% reduction in risk. CONCLUSION: An optimal baseline ADC value is a functional imaging response biomarker that has higher discriminatory power to predict tumor response and prolonged survival following chemoembolization in HCC patients.

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Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13102499 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2499

Author(s):

Lisanne Noordam ◽

Zhouhong Ge ◽

Hadiye Özturk ◽

Michail Doukas ◽

Shanta Mancham ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Occult Metastasis ◽

Recurrence Rates ◽

Curative Intent ◽

Cancer Testis Antigens ◽

Negative Prognostic Factor ◽

Increased Risk ◽

Hcc Recurrence ◽

Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

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SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

Cells ◽

10.3390/cells10010178 ◽

2021 ◽

Vol 10 (1) ◽

pp. 178

Author(s):

Jiann Ruey Ong ◽

Oluwaseun Adebayo Bamodu ◽

Nguyen Viet Khang ◽

Yen-Kuang Lin ◽

Chi-Tai Yeh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Metabolism ◽

Interaction Analysis ◽

Normal Liver ◽

Diagnostic Value ◽

Vital Role ◽

Regulation Of Transcription ◽

Dependent Manner ◽

Post Translational Modification ◽

Characteristic Analysis

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA−LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with ‘normal’ paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

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Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

Cytogenetic and Genome Research ◽

10.1159/000512264 ◽

2020 ◽

Vol 160 (11-12) ◽

pp. 650-658

Author(s):

Yichen Le ◽

Yi He ◽

Meirong Bai ◽

Ying Wang ◽

Jiaxue Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Cancer Progression ◽

Normal Liver ◽

Cell Growth And Migration ◽

And Migration ◽

Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

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FXYD6 overexpression in HBV-related hepatocellular carcinoma with cirrhosis

Open Life Sciences ◽

10.1515/biol-2020-0027 ◽

2020 ◽

Vol 15 (1) ◽

pp. 259-266

Author(s):

Xiongfei Chen ◽

Lishuang Ding ◽

Deshuai Kong ◽

Xiulei Zhao ◽

Lili Liao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Early Recurrence ◽

Tumor Diameter ◽

Tumor Number ◽

B Virus ◽

Expression Rate ◽

Polymerase Chain ◽

And Gender ◽

Liver Tissues

AbstractObjectiveThe aim of this study was to investigate the expression of FXYD domain-containing ion transport regulator 6 (FXYD6) mRNA and protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues with cirrhosis, the corresponding paracancerous tissues and the normal liver tissues, and to explore the clinical significance of FXYD6 expression in HBV-related HCC with cirrhosis.MethodsThe FXYD6 mRNA and protein were examined by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively.ResultsThe FXYD6 mRNA in HBV-related HCC tissues was significantly higher than that in the cirrhosis tissues or that in the normal liver tissues. The positive expression rate of FXYD6 protein was statistically higher in HBV-related HCC tissues than that in HBV-related cirrhosis or that in normal liver tissues. There was no significant correlation between the expression of FXYD6 protein and gender, age, histological differentiation, tumor diameter, tumor number, integrity of tumor capsule or not and alpha fetoprotein (AFP) concentration in serum, but the protein expression was associated with microvascular invasion, pathological stage, and early recurrence after operation within 1 year.ConclusionFXYD6 might be involved in hepatocyte carcinogenesis and tumor progression in HBV-related HCC with cirrhosis and indicated a poor prognosis.

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Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-021-08104-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jian-Yao Wang ◽

Xiang-Kun Wang ◽

Guang-Zhi Zhu ◽

Xin Zhou ◽

Jun Yao ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Tumor Tissue ◽

Bioinformatics Analysis ◽

Mrna Level ◽

Normal Liver ◽

Predictive Index ◽

Expression Levels ◽

Interactive Analysis ◽

Diagnostic Values

Abstract Backgroud In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.

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Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

Insights into Imaging ◽

10.1186/s13244-021-01004-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sofia Amante ◽

Filipa Santos ◽

Teresa Margarida Cunha

Keyword(s):

Ovarian Cancer ◽

Serous Carcinoma ◽

Low Grade ◽

Resonance Imaging ◽

Clinicopathologic Characteristics ◽

Borderline Tumour ◽

Molecular Features ◽

Serous Epithelial Ovarian Cancer ◽

The Difference

AbstractLow-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

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