High Expression of Macrophage Colony-Stimulating Factor in Peritumoral Liver Tissue Is Associated With Poor Survival After Curative Resection of Hepatocellular Carcinoma

2008 ◽  
Vol 26 (16) ◽  
pp. 2707-2716 ◽  
Author(s):  
Xiao-Dong Zhu ◽  
Ju-Bo Zhang ◽  
Peng-Yuan Zhuang ◽  
Hong-Guang Zhu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tissue ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Intrahepatic Metastasis ◽  
Poor Survival ◽  
Large Tumor ◽  
Macrophage Colony

Purpose To investigate prognostic values of the intratumoral and peritumoral expression of macrophage colony-stimulating factors (M-CSF) in hepatocellular carcinoma (HCC) patients after curative resection. Patients and Methods Expression of M-CSF and density of macrophages (MΦ) were assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 105 patients who had undergone hepatectomy for histologically proven HCC. Prognostic value of these and other clinicopathologic factors was evaluated. Results Neither intratumoral M-CSF nor MΦ density was associated with overall survival (OS) or disease-free survival (DFS). High peritumoral M-CSF and MΦ density, which correlated with large tumor size, presence of intrahepatic metastasis, and high TNM stage, were independent prognostic factors for both OS (P = .001 and P < .001, respectively) and DFS (P = .001 and P = .003, respectively) and affected incidence of early recurrence. In a small HCC subset, peritumoral M-CSF was also correlated with both OS and DFS (P = .038 and P = .001, respectively). The combination of peritumoral M-CSF and MΦ had a better power to predict the patients' death and disease recurrence (P < .001 for both). Conclusion High peritumoral M-CSF and MΦ were associated with HCC progression, disease recurrence, and poor survival after hepatectomy, highlighting the importance of peritumoral tissue in the recurrence and metastasis of HCC. M-CSF and MΦ may be targets of postoperative adjuvant therapy.

scholarly journals LI-RADS category 5 hepatocellular carcinoma: preoperative gadoxetic acid–enhanced MRI for early recurrence risk stratification after curative resection

2020 ◽  
Author(s):  
Hong Wei ◽  
Hanyu Jiang ◽  
Tianying Zheng ◽  
Zhen Zhang ◽  
Caiwei Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Gadoxetic Acid ◽  
Mri Findings ◽  
Free Survival ◽  
Enhanced Mri ◽  
Disease Free ◽  
Corona Enhancement

Abstract Objectives To explore the role of preoperative gadoxetic acid–enhanced MRI in stratifying the risk of early recurrence in patients with LR-5 hepatocellular carcinoma (HCC) by LI-RADS v2018 after curative resection. Methods Between July 2015 and August 2018, this study evaluated consecutive treatment-naïve at-risk LR-5 HCC patients who underwent gadoxetic acid–enhanced MRI examination within 2 weeks before curative resection. The Cox regression analysis was performed to identify potential predictors of early recurrence. Disease-free survival (DFS) rates were analyzed and compared by using the Kaplan-Meier method and log-rank tests. Results Fifty-three of 103 (51.5%) patients experienced early recurrence. Three MRI findings were significantly associated with early recurrence: corona enhancement (hazard ratio [HR]: 2.116; p = 0.013), peritumoral hypointensity on hepatobiliary phase (HBP) (HR: 2.262; p = 0.007), and satellite nodule (HR: 2.777; p = 0.005). An additional risk factor was AFP level > 400 ng/mL (HR: 1.975; p = 0.016). Based on the number of MRI predictors, LR-5 HCC patients were stratified into three subgroups: LR-5a (60/103; no predictor), LR-5b (26/103; one predictor), and LR-5c (17/103; two or three predictors), with low, medium, and high risk of early recurrence, respectively. The 2-year DFS rate of LR-5a, LR-5b, and LR-5c patients was 65.0%, 38.5%, and 5.9%, respectively, while the corresponding median DFS was undefined, 17.1 months, and 5.1 months, respectively (p < 0.001). Conclusions In at-risk LR-5 HCC patients, corona enhancement, peritumoral hypointensity on HBP, and satellite nodule could be used to preoperatively stratify the risk of early recurrence after hepatectomy. Key Points • Corona enhancement, peritumoral hypointensity on HBP, satellite nodule, and serum AFP level > 400 ng/mL were significant predictors of early recurrence in patients with LR-5 HCC after hepatectomy. • Based on the number of predictive MRI findings, LR-5 HCC patients could be preoperatively stratified into three subgroups: LR-5a, LR-5b, and LR-5c, with significantly different risk of early recurrence and disease-free survival. • Preoperative risk stratification is essential for the identification of patients at increased risk of postoperative early recurrence, which may contribute to risk-based personalized management for LR-5 HCC patients.

A long non-coding RNA-based signature predicts early recurrence in hepatocellular carcinoma

2021 ◽  
pp. 1-10
Author(s):  
Shuai He ◽  
Jin-Feng Li ◽  
Hao Tian ◽  
Ye Sang ◽  
Xiao-Jing Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Risk Model ◽  
Cox Regression ◽  
Early Recurrence ◽  
Support Vector ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

BACKGROUND: Early recurrence is the main obstacle for long-term survival of hepatocellular carcinoma (HCC) patients after curative resection. OBJECTIVE: We aimed to develop a long non-coding RNA (lncRNA) based signature to predict early recurrence. METHODS: Using bioinformatics analysis and quantitative reverse transcription PCR (RT-qPCR), we screened for lncRNA candidates that were abnormally expressed in HCC. The expression levels of candidate lncRNAs were analyzed in HCC tissues from 160 patients who underwent curative resection, and a risk model for the prediction of recurrence within 1 year (early recurrence) of HCCs was constructed with linear support vector machine (SVM). RESULTS: A lncRNA-based classifier (Clnc), which contained nine differentially expressed lncRNAs including AF339810, AK026286, BC020899, HEIH, HULC, MALAT1, PVT1, uc003fpg, and ZFAS1 was constructed. In the test set, this classifier reliably predicted early recurrence (AUC, 0.675; sensitivity, 72.0%; specificity, 63.1%) with an odds ratio of 4.390 (95% CI, 2.120–9.090). Clnc showed higher accuracy than traditional clinical features, including tumor size, portal vein tumor thrombus (PVTT) in predicting early recurrence (AUC, 0.675 vs 0.523 vs 0.541), and had much higher sensitivity than Barcelona Clinical Liver Cancer (BCLC; 72.0% vs 50.0%), albeit their AUCs were comparable (0.675 vs 0.678). Moreover, combining Clnc with BCLC significantly increased the AUC, compared with Clnc or BCLC alone in predicting early recurrence (all P< 0.05). Finally, logistic and Cox regression analysis suggested that Clnc was an independent prognostic factor and associated with the early recurrence and recurrence-free survival of HCC patients after resection, respectively (all P= 0.001). CONCLUSIONS: Our lncRNA-based classifier Clnc can predict early recurrence of patients undergoing surgical resection of HCC.

scholarly journals Animal model of intrahepatic metastasis of hepatocellular carcinoma: establishment and characteristic

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xuemei Li ◽  
Jike Hu ◽  
Baohong Gu ◽  
Maswikiti Ewetse Paul ◽  
Bofang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Cell Line ◽  
Cell Lines ◽  
Intrahepatic Metastasis ◽  
Model Systems ◽  
Large Tumor ◽  
Important Direction ◽  
Disease Study

Abstract One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.

HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling

2019 ◽  
Vol 133 (14) ◽  
pp. 1645-1662 ◽  
Author(s):  
Yan-rong Zhao ◽  
Ji-long Wang ◽  
Cong Xu ◽  
Yi-ming Li ◽  
Bo Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heart Development ◽  
Poor Prognosis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Intrahepatic Metastasis ◽  
Mesenchymal Transition

Abstract Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial–mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo. Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes β-catenin expression and maintains its stability, leading to intracellular β-catenin accumulation, β-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that β-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/β-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.

scholarly journals Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy

2018 ◽  
Vol 267 (5) ◽  
pp. 922-928 ◽  
Author(s):  
David D. Aufhauser ◽  
Eran Sadot ◽  
Douglas R. Murken ◽  
Kevin Eddinger ◽  
Maarouf Hoteit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Partial Hepatectomy ◽  
Early Recurrence ◽  
Intrahepatic Metastasis ◽  
Recurrence Rates
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