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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Liver Transplantation | Research

Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation

Authors: Yangyang Wang, Wei Zhang, Hongbin Ge, Xu Han, Jiangchao Wu, Xuqi Sun, Ke Sun, Wanyue Cao, Chao Huang, Jingsong Li, Qi Zhang, Tingbo Liang

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Tumor micronecrosis is a histopathological feature predicting poor prognosis in patients with hepatocellular carcinoma (HCC) who underwent liver resection. However, the role of tumor micronecrosis in liver transplantation remains unclear.

Methods

We retrospectively reviewed patients with HCC who underwent liver transplantation between January 2015 and December 2021 at our center. We then classified them into micronecrosis(−) and micronecrosis(+) groups and compared their recurrence-free survival (RFS) and overall survival (OS). We identified independent prognostic factors using Cox regression analysis and calculated the area under the receiver operating characteristic curve (AUC) to evaluate the predictive value of RFS for patients with HCC after liver transplantation.

Results

A total of 370 cases with evaluable histological sections were included. Patients of the micronecrosis(+) group had a significantly shorter RFS than those of the micronecrosis(−) group (P = 0.037). Shorter RFS and OS were observed in micronecrosis(+) patients without bridging treatments before liver transplantation (P = 0.002 and P = 0.007), while no differences were detected in those with preoperative antitumor therapies that could cause iatrogenic tumor necrosis. Tumor micronecrosis improved the AUC of Milan criteria (0.77–0.79), the model for end-stage liver disease score (0.70–0.76), and serum alpha-fetoprotein (0.63–0.71) for the prediction of prognosis after liver transplantation.

Conclusion

Patients with HCC with tumor micronecrosis suffer from a worse prognosis than those without this feature. Tumor micronecrosis can help predict RFS after liver transplantation. Therefore, patients with HCC with tumor micronecrosis should be treated with adjuvant therapy and closely followed after liver transplantation.

Clinical trials registration

Not Applicable.
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRef Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRef
2.
go back to reference Bruix J, Sherman M. American Association for the Study of liver D. management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRef Bruix J, Sherman M. American Association for the Study of liver D. management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.CrossRef
3.
go back to reference Dutkowski P, Linecker M, DeOliveira ML, Mullhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology. 2015;148(2):307–23.CrossRef Dutkowski P, Linecker M, DeOliveira ML, Mullhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology. 2015;148(2):307–23.CrossRef
4.
go back to reference Sugawara Y, Hibi T. Surgical treatment of hepatocellular carcinoma. Biosci Trends. 2021;15(3):138–41.CrossRef Sugawara Y, Hibi T. Surgical treatment of hepatocellular carcinoma. Biosci Trends. 2021;15(3):138–41.CrossRef
5.
go back to reference Gunsar F. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Exp Clin Transplant. 2017;15(Suppl 2):59–64. Gunsar F. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Exp Clin Transplant. 2017;15(Suppl 2):59–64.
6.
go back to reference Barreto SG, Strasser SI, McCaughan GW, Fink MA, Jones R, McCall J, et al. Expansion of liver transplantation criteria for hepatocellular carcinoma from Milan to UCSF in Australia and New Zealand and justification for Metroticket 2.0. Cancers (Basel). 2022;14(11):2777.CrossRef Barreto SG, Strasser SI, McCaughan GW, Fink MA, Jones R, McCall J, et al. Expansion of liver transplantation criteria for hepatocellular carcinoma from Milan to UCSF in Australia and New Zealand and justification for Metroticket 2.0. Cancers (Basel). 2022;14(11):2777.CrossRef
7.
go back to reference Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, et al. MELD 3.0: the model for end-stage liver disease updated for the modern era. Gastroenterology. 2021;161(6):1887–1895 e1884.CrossRef Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, et al. MELD 3.0: the model for end-stage liver disease updated for the modern era. Gastroenterology. 2021;161(6):1887–1895 e1884.CrossRef
8.
go back to reference Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRef Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRef
9.
go back to reference Shimamura T, Goto R, Watanabe M, Kawamura N, Takada Y. Liver transplantation for hepatocellular carcinoma: how should we improve the thresholds? Cancers (Basel). 2022;14(2):419.CrossRef Shimamura T, Goto R, Watanabe M, Kawamura N, Takada Y. Liver transplantation for hepatocellular carcinoma: how should we improve the thresholds? Cancers (Basel). 2022;14(2):419.CrossRef
10.
go back to reference Karsch-Bluman A, Benny O. Necrosis in the tumor microenvironment and its role in Cancer recurrence. Adv Exp Med Biol. 2020;1225:89–98.CrossRef Karsch-Bluman A, Benny O. Necrosis in the tumor microenvironment and its role in Cancer recurrence. Adv Exp Med Biol. 2020;1225:89–98.CrossRef
11.
go back to reference Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39.CrossRef Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39.CrossRef
12.
go back to reference Atanasov G, Dietel C, Feldbrugge L, Benzing C, Krenzien F, Brandl A, et al. Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma. Oncoimmunology. 2017;6(8):e1331806.CrossRef Atanasov G, Dietel C, Feldbrugge L, Benzing C, Krenzien F, Brandl A, et al. Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma. Oncoimmunology. 2017;6(8):e1331806.CrossRef
13.
go back to reference Kuroe T, Watanabe R, Kojima M, Morisue R, Sugano M, Kuwata T, et al. Evaluation of the morphological features and unfavorable prognostic impact of dirty necrosis in renal cell carcinoma. J Cancer Res Clin Oncol. 2021;147(4):1089–100.CrossRef Kuroe T, Watanabe R, Kojima M, Morisue R, Sugano M, Kuwata T, et al. Evaluation of the morphological features and unfavorable prognostic impact of dirty necrosis in renal cell carcinoma. J Cancer Res Clin Oncol. 2021;147(4):1089–100.CrossRef
14.
go back to reference Tata A, Woolman M, Ventura M, Bernards N, Ganguly M, Gribble A, et al. Rapid detection of necrosis in breast Cancer with desorption electrospray ionization mass spectrometry. Sci Rep. 2016;6:35374.CrossRef Tata A, Woolman M, Ventura M, Bernards N, Ganguly M, Gribble A, et al. Rapid detection of necrosis in breast Cancer with desorption electrospray ionization mass spectrometry. Sci Rep. 2016;6:35374.CrossRef
15.
go back to reference Wei T, Zhang XF, Bagante F, Ratti F, Marques HP, Silva S, et al. Tumor necrosis impacts prognosis of patients undergoing curative-intent hepatocellular carcinoma. Ann Surg Oncol. 2021;28(2):797–805.CrossRef Wei T, Zhang XF, Bagante F, Ratti F, Marques HP, Silva S, et al. Tumor necrosis impacts prognosis of patients undergoing curative-intent hepatocellular carcinoma. Ann Surg Oncol. 2021;28(2):797–805.CrossRef
16.
go back to reference Ye Q, Zhang Q, Tian Y, Zhou T, Ge H, Wu J, et al. Method of tumor pathological micronecrosis quantification via deep learning from label fuzzy proportions. IEEE J Biomed Health Inform. 2021;25(9):3288–99.CrossRef Ye Q, Zhang Q, Tian Y, Zhou T, Ge H, Wu J, et al. Method of tumor pathological micronecrosis quantification via deep learning from label fuzzy proportions. IEEE J Biomed Health Inform. 2021;25(9):3288–99.CrossRef
17.
go back to reference Wang Y, Ge H, Hu M, Pan C, Ye M, Yadav DK, et al. Histological tumor micronecrosis in resected specimens after R0 hepatectomy for hepatocellular carcinomas is a factor in determining adjuvant TACE: a retrospective propensity score-matched study. Int J Surg. 2022;105:106852.CrossRef Wang Y, Ge H, Hu M, Pan C, Ye M, Yadav DK, et al. Histological tumor micronecrosis in resected specimens after R0 hepatectomy for hepatocellular carcinomas is a factor in determining adjuvant TACE: a retrospective propensity score-matched study. Int J Surg. 2022;105:106852.CrossRef
18.
go back to reference Cong WM, Bu H, Chen J, Dong H, Zhu YY, Feng LH, et al. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol. 2016;22(42):9279–87.CrossRef Cong WM, Bu H, Chen J, Dong H, Zhu YY, Feng LH, et al. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol. 2016;22(42):9279–87.CrossRef
19.
go back to reference Le NQK, Do DT, Nguyen TT, Le QA. A sequence-based prediction of Kruppel-like factors proteins using XGBoost and optimized features. Gene. 2021;787:145643.CrossRef Le NQK, Do DT, Nguyen TT, Le QA. A sequence-based prediction of Kruppel-like factors proteins using XGBoost and optimized features. Gene. 2021;787:145643.CrossRef
20.
go back to reference Le NQK, Kha QH, Nguyen VH, Chen YC, Cheng SJ, Chen CY. Machine learning-based Radiomics signatures for EGFR and KRAS mutations prediction in non-small-cell lung Cancer. Int J Mol Sci. 2021;22(17):9254.CrossRef Le NQK, Kha QH, Nguyen VH, Chen YC, Cheng SJ, Chen CY. Machine learning-based Radiomics signatures for EGFR and KRAS mutations prediction in non-small-cell lung Cancer. Int J Mol Sci. 2021;22(17):9254.CrossRef
21.
go back to reference Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010;5(9):1315–6.CrossRef Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010;5(9):1315–6.CrossRef
22.
go back to reference Richards CH, Mohammed Z, Qayyum T, Horgan PG, McMillan DC. The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review. Future Oncol. 2011;7(10):1223–35.CrossRef Richards CH, Mohammed Z, Qayyum T, Horgan PG, McMillan DC. The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review. Future Oncol. 2011;7(10):1223–35.CrossRef
23.
go back to reference Atanasov G, Schierle K, Hau HM, Dietel C, Krenzien F, Brandl A, et al. Prognostic significance of tumor necrosis in hilar Cholangiocarcinoma. Ann Surg Oncol. 2017;24(2):518–25.CrossRef Atanasov G, Schierle K, Hau HM, Dietel C, Krenzien F, Brandl A, et al. Prognostic significance of tumor necrosis in hilar Cholangiocarcinoma. Ann Surg Oncol. 2017;24(2):518–25.CrossRef
24.
go back to reference Kollmann D, Selzner N, Selzner M. Bridging to liver transplantation in HCC patients. Langenbeck's Arch Surg. 2017;402(6):863–71.CrossRef Kollmann D, Selzner N, Selzner M. Bridging to liver transplantation in HCC patients. Langenbeck's Arch Surg. 2017;402(6):863–71.CrossRef
25.
go back to reference Lee SW, Yen CL, Cheng YC, Shun Yang S, Lee TY. The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma. Medicine (Baltimore). 2022;101(41):e30875.CrossRef Lee SW, Yen CL, Cheng YC, Shun Yang S, Lee TY. The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma. Medicine (Baltimore). 2022;101(41):e30875.CrossRef
26.
go back to reference Kardashian A, Florman SS, Haydel B, Ruiz RM, Klintmalm GB, Lee DD, Taner CB, Aucejo F, Tevar AD, Humar A, Verna EC, Halazun KJ, Chapman WC, Vachharajani N, Hoteit M, Levine MH, Nguyen MH, Melcher ML, Langnas AN, Carney CA, Mobley C, Ghobrial M, Amundsen B, Markmann JF, Sudan DL, Jones CM, Berumen J, Hemming AW, Hong JC, Kim J, Zimmerman MA, Nydam TL, Rana A, Kueht ML, Fishbein TM, Markovic D, Busuttil RW, Agopian VG. Liver transplantation outcomes in a U.S. multicenter cohort of 789 patients with hepatocellular carcinoma presenting beyond Milan criteria. Hepatology 2020, 72(6):2014–2028. Kardashian A, Florman SS, Haydel B, Ruiz RM, Klintmalm GB, Lee DD, Taner CB, Aucejo F, Tevar AD, Humar A, Verna EC, Halazun KJ, Chapman WC, Vachharajani N, Hoteit M, Levine MH, Nguyen MH, Melcher ML, Langnas AN, Carney CA, Mobley C, Ghobrial M, Amundsen B, Markmann JF, Sudan DL, Jones CM, Berumen J, Hemming AW, Hong JC, Kim J, Zimmerman MA, Nydam TL, Rana A, Kueht ML, Fishbein TM, Markovic D, Busuttil RW, Agopian VG. Liver transplantation outcomes in a U.S. multicenter cohort of 789 patients with hepatocellular carcinoma presenting beyond Milan criteria. Hepatology 2020, 72(6):2014–2028.
27.
go back to reference Najmi Varzaneh F, Pandey A, Aliyari Ghasabeh M, Shao N, Khoshpouri P, Pandey P, et al. Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation. Eur Radiol. 2018;28(7):3032–40.CrossRef Najmi Varzaneh F, Pandey A, Aliyari Ghasabeh M, Shao N, Khoshpouri P, Pandey P, et al. Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation. Eur Radiol. 2018;28(7):3032–40.CrossRef
28.
go back to reference Yao FY, Kerlan RK Jr, Hirose R, Davern TJ 3rd, Bass NM, Feng S, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48(3):819–27.CrossRef Yao FY, Kerlan RK Jr, Hirose R, Davern TJ 3rd, Bass NM, Feng S, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48(3):819–27.CrossRef
29.
go back to reference Gyori GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg. 2017;49(5):236–43.CrossRef Gyori GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg. 2017;49(5):236–43.CrossRef
30.
go back to reference Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, Group OLTfHC. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13(1):e11–22.CrossRef Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, Group OLTfHC. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13(1):e11–22.CrossRef
31.
go back to reference Chaiteerakij R, Zhang X, Addissie BD, Mohamed EA, Harmsen WS, Theobald PJ, et al. Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl. 2015;21(5):599–606.CrossRef Chaiteerakij R, Zhang X, Addissie BD, Mohamed EA, Harmsen WS, Theobald PJ, et al. Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl. 2015;21(5):599–606.CrossRef
32.
go back to reference Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRef Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRef
33.
go back to reference Lee S, Kim KW, Jeong WK, Kim MJ, Choi GH, Choi JS, et al. Gadoxetic acid-enhanced MRI as a predictor of recurrence of HCC after liver transplantation. Eur Radiol. 2020;30(2):987–95.CrossRef Lee S, Kim KW, Jeong WK, Kim MJ, Choi GH, Choi JS, et al. Gadoxetic acid-enhanced MRI as a predictor of recurrence of HCC after liver transplantation. Eur Radiol. 2020;30(2):987–95.CrossRef
34.
go back to reference Luo X, Leanza J, Massie AB, Garonzik-Wang JM, Haugen CE, Gentry SE, et al. MELD as a metric for survival benefit of liver transplantation. Am J Transplant. 2018;18(5):1231–7.CrossRef Luo X, Leanza J, Massie AB, Garonzik-Wang JM, Haugen CE, Gentry SE, et al. MELD as a metric for survival benefit of liver transplantation. Am J Transplant. 2018;18(5):1231–7.CrossRef
35.
go back to reference Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, Fan J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology. 2018;154(1):128–39.CrossRef Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, Fan J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology. 2018;154(1):128–39.CrossRef
36.
go back to reference Agopian VG, Harlander-Locke M, Zarrinpar A, Kaldas FM, Farmer DG, Yersiz H, et al. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg. 2015;220(4):416–27.CrossRef Agopian VG, Harlander-Locke M, Zarrinpar A, Kaldas FM, Farmer DG, Yersiz H, et al. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg. 2015;220(4):416–27.CrossRef
37.
go back to reference Huang D, Shen Y, Zhang W, Guo C, Liang T, Bai X. A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study. BMC Cancer. 2021;21(1):280.CrossRef Huang D, Shen Y, Zhang W, Guo C, Liang T, Bai X. A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study. BMC Cancer. 2021;21(1):280.CrossRef
38.
go back to reference Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.CrossRef Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.CrossRef
39.
go back to reference Ehling J, Bartneck M, Wei X, Gremse F, Fech V, Mockel D, et al. CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis. Gut. 2014;63(12):1960–71.CrossRef Ehling J, Bartneck M, Wei X, Gremse F, Fech V, Mockel D, et al. CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis. Gut. 2014;63(12):1960–71.CrossRef
40.
go back to reference Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, et al. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50(1):261–74.CrossRef Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, et al. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50(1):261–74.CrossRef
41.
go back to reference Liu H, Ling CC, Yeung WHO, Pang L, Liu J, Zhou J, et al. Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling. Cell Death Dis. 2021;12(5):489.CrossRef Liu H, Ling CC, Yeung WHO, Pang L, Liu J, Zhou J, et al. Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling. Cell Death Dis. 2021;12(5):489.CrossRef
42.
go back to reference Ouzounova M, Lee E, Piranlioglu R, El Andaloussi A, Kolhe R, Demirci MF, et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun. 2017;8:14979.CrossRef Ouzounova M, Lee E, Piranlioglu R, El Andaloussi A, Kolhe R, Demirci MF, et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun. 2017;8:14979.CrossRef
43.
go back to reference Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008;8(12):967–75.CrossRef Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008;8(12):967–75.CrossRef
44.
go back to reference Chen J, Chen J, Huang J, Li Z, Gong Y, Zou B, et al. HIF-2alpha upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Aging (Albany NY). 2019;11(23):10839–60.CrossRef Chen J, Chen J, Huang J, Li Z, Gong Y, Zou B, et al. HIF-2alpha upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Aging (Albany NY). 2019;11(23):10839–60.CrossRef
45.
go back to reference Kim I, Choi S, Yoo S, Lee M, Kim IS. Cancer-associated fibroblasts in the hypoxic tumor microenvironment. Cancers (Basel). 2022;14(14):3321.CrossRef Kim I, Choi S, Yoo S, Lee M, Kim IS. Cancer-associated fibroblasts in the hypoxic tumor microenvironment. Cancers (Basel). 2022;14(14):3321.CrossRef
46.
go back to reference Joshi S, Singh AR, Zulcic M, Durden DL. A macrophage-dominant PI3K isoform controls hypoxia-induced HIF1alpha and HIF2alpha stability and tumor growth, angiogenesis, and metastasis. Mol Cancer Res. 2014;12(10):1520–31.CrossRef Joshi S, Singh AR, Zulcic M, Durden DL. A macrophage-dominant PI3K isoform controls hypoxia-induced HIF1alpha and HIF2alpha stability and tumor growth, angiogenesis, and metastasis. Mol Cancer Res. 2014;12(10):1520–31.CrossRef
Metadata
Title
Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation
Authors
Yangyang Wang
Wei Zhang
Hongbin Ge
Xu Han
Jiangchao Wu
Xuqi Sun
Ke Sun
Wanyue Cao
Chao Huang
Jingsong Li
Qi Zhang
Tingbo Liang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10550-w

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