Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

Atanasov, Georgi; Dino, Karoline; Schierle, Katrin; Dietel, Corinna; Aust, Gabriela; Pratschke, Johann; Seehofer, Daniel; Schmelzle, Moritz; Hau, Hans-Michael

doi:10.1186/s12957-019-1756-8

Cited by 18 publications

(13 citation statements)

References 46 publications

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“…A recent study revealed that the presence of tumor necrosis is associated with an advanced tumor stage, HCC recurrence, and patient survival after curative hepatectomy for HCC [29]. In agreement with these ndings, we also identi ed necrotic HCC to be associated with a high rate of EHR.…”

Section: Analysis Of Factors Associated With Ehrsupporting

confidence: 88%

Clinical features of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma: simple parameters predicting extrahepatic recurrence

Yoon

Lee

Kim

et al. 2021

Preprint

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Background Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. Methods This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate analysis via Cox-regression was performed to identify the variables associated with EHR. Results EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively.. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, bile duct invasion, tumor necrosis, sum of tumor size > 7 cm, macrovascular invasion, first recurrence free survival < 1 year, and serum alpha fetoprotein > 400 IU/mL during recurrence were predictive of EHR. Four risk levels and their respective EHR were defined: very low risk, 2-/5-year, 0.7%/14.2%; low risk, 2-/5-year, 6.4%/31.0%; intermediate risk, 2-/5-year, 21.9%/73.1%; and high risk, 2-/3-year, 70.8%/100.0%. Conclusion Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

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Section: Analysis Of Factors Associated With Ehrsupporting

confidence: 88%

Clinical features of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma: simple parameters predicting extrahepatic recurrence

Yoon

Lee

Kim

et al. 2021

Preprint

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“…Advanced HCC implicated multiple cellular pathways and played central roles in tumor metastasis and recurrence. Activity signaling cascade in HCC, including Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR, which promotes transcription of genes involved in tumor proliferation [43]. Sorafenib, a TKI (tyrosine kinases inhibitor) drug, was the first multikinase inhibitor authorized for the medicine of HCC.…”

Section: Discussionmentioning

confidence: 99%

MiR-29a Curbs Hepatocellular Carcinoma Incidence via Targeting of HIF-1α and ANGPT2

Huang

Lian

Wang

et al. 2022

IJMS

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A high-fat diet is responsible for hepatic fat accumulation that sustains chronic liver damage and increases the risks of steatosis and hepatocellular carcinoma (HCC). MicroRNA-29a (miR-29a), a key regulator of cellular behaviors, is present in anti-fibrosis and modulator tumorigenesis. However, the increased transparency of the correlation between miR-29a and the progression of human HCC is still further investigated. In this study, we predicted HIF-1α and ANGPT2 as regulators of HCC by the OncoMir cancer database and showed a strong positive correlation with HIF-1α and ANGPT2 gene expression in HCC patients. Mice fed the western diet (WD) while administered CCl4 for 25 weeks induced chronic liver damage and higher HCC incidence than without fed WD mice. HCC section staining revealed signaling upregulation in ki67, severe fibrosis, and steatosis in WD and CCl4 mice and detected Col3a1 gene expressions. HCC tissues significantly attenuated miR-29a but increased in HIF-1α, ANGPT2, Lox, Loxl2, and VEGFA expression. Luciferase activity analysis confirms that miR-29a specific binding 3′UTR of HIF-1α and ANGPT2 to repress expression. In summary, miR-29a control HIF-1α and ANGPT2 signaling in HCC formation. This study insight into a novel molecular pathway by which miR-29a targeting HIF-1α and ANGPT2 counteracts the incidence of HCC development.

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“…Yang et al reported that EHR was more common among patients with vascular invasion, intrahepatic metastasis, and more advanced HCC stages 11 . A recent study revealed that the presence of tumor necrosis was associated with an advanced tumor stage, HCC recurrence, and patient survival after curative hepatectomy for HCC 23 . In agreement with these findings, we also identified that necrotic HCC was associated with a high rate of EHR.…”

Section: Discussionmentioning

confidence: 99%

Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma

Yoon

Lee

Kim

et al. 2021

Sci Rep

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Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

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Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

Cited by 18 publications

References 46 publications

Clinical features of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma: simple parameters predicting extrahepatic recurrence

Clinical features of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma: simple parameters predicting extrahepatic recurrence

MiR-29a Curbs Hepatocellular Carcinoma Incidence via Targeting of HIF-1α and ANGPT2

Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma

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