Pulmonary metastasis of hepatocellular carcinoma: pathogenesis and therapeutic advances

doi:10.16139/j.1007-9610.2022.02.018

Abstract

Abstract:

In recent years, the survival of patients increased with development of treatment modalities for hepatocellular carcinoma(HCC). However, the incidence of distant metastasis was gradually increasing to make the prognosis of patients with HCC worse. Lungs are the most common distant metastatic organs from HCC. Therapy of pulmonary metastasis from HCC was still disappointing with the median overall survival less than 1 year for individual differences in patients and tumor heterogeneity. Currently, there was without standard treatment for pulmonary metastases from HCC, and the patients were treated according to the treatment guidelines of advanced HCC combined with lung cancer. Although studies on invasion and metastasis of HCC emerged in a few decades, the detail pathogenesis of lung metastasis remains unclear. This article will summarize the pathogenesis and therapeutic advances of pulmonary metastasis from HCC and emphasize the importance of intrahepatic lesion control and management of pulmonary metastases.

Key words: Hepatocellular carcinoma, pulmonary metastasis, Tumor microenvironment

CLC Number:

GUAN Tao, ZHANG Ti, WANG Lu. Pulmonary metastasis of hepatocellular carcinoma: pathogenesis and therapeutic advances[J]. Journal of Surgery Concepts & Practice, 2022, 27(02): 180-184.

References 39

[1]	Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression[J]. Cancer Res, 2019, 79(18):4557-4566.
[2]	Lu LC, Hsu CH, Hsu C, et al. Tumor heterogeneity in hepatocellular carcinoma: facing the challenges[J]. Liver Cancer, 2016, 5(2):128-138. doi: 10.1159/000367754 pmid: 27386431
[3]	Martins-Filho SN, Alves VAF, Wakamatsu A, et al. A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites[J]. Histopathology, 2019, 74(5):718-730. doi: 10.1111/his.13809 pmid: 30636011
[4]	Ouyang L, Lee J, Park CK, et al. Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas[J]. BMC Med Genomics, 2014, 7:2. doi: 10.1186/1755-8794-7-2 pmid: 24405831
[5]	Bykov VJN, Eriksson SE, Bianchi J, et al. Targeting mutant p53 for efficient cancer therapy[J]. Nat Rev Cancer, 2018, 18(2):89-102. doi: 10.1038/nrc.2017.109 URL
[6]	Zheng Y, Lv P, Wang S, et al. LncRNA PLAC2 upregulates p53 to induce hepatocellular carcinoma cell apoptosis[J]. Gene, 2019, 712:143944.
[7]	Gross-Goupil M, Riou P, Emile JF, et al. Analysis of chromosomal instability in pulmonary or liver metastases and matched primary hepatocellular carcinoma after orthotopic liver transplantation[J]. Int J Cancer, 2003, 104(6):745-751. pmid: 12640682
[8]	Luo YD, Fang L, Yu HQ, et al. p53 haploinsufficiency and increased mTOR signalling define a subset of aggressive hepatocellular carcinoma[J]. J Hepatol, 2021, 74(1):96-108. doi: 10.1016/j.jhep.2020.07.036 URL
[9]	Wu Q, Zhou L, Lv D, et al. Exosome-mediated communication in the tumor microenvironment contributes to he-patocellular carcinoma development and progression[J]. J Hematol Oncol, 2019, 12(1):53. doi: 10.1186/s13045-019-0739-0 URL
[10]	Ge Y, Mu W, Ba Q, et al. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application[J]. Cancer Lett, 2020, 477:41-48. doi: 10.1016/j.canlet.2020.02.003 URL
[11]	Ye L, Zhang Q, Cheng Y, et al. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1⁺ regulatory B cell expansion[J]. J Immunother Cancer, 2018, 6(1):145. doi: 10.1186/s40425-018-0451-6 URL
[12]	Fang T, Lv H, Lv G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J]. Nat Commun, 2018, 9(1):191. doi: 10.1038/s41467-017-02583-0 URL
[13]	Sun YF, Guo W, Xu Y, et al. Circulating tumor cells from different vascular sites exhibit spatial heterogeneity in epithelial and mesenchymal composition and distinct clinical significance in hepatocellular carcinoma[J]. Clin Cancer Res, 2018, 24(3):547-559. doi: 10.1158/1078-0432.CCR-17-1063 URL
[14]	Li J, King MR. Adhesion receptors as therapeutic targets for circulating tumor cells[J]. Front Oncol, 2012, 2:79.
[15]	Sprouse ML, Welte T, Boral D, et al. PMN-MDSCs enhance CTC metastatic properties through reciprocal in-teractions via ROS/Notch/Nodal signaling[J]. Int J Mol Sci, 2019, 20(8):1916. doi: 10.3390/ijms20081916 URL
[16]	RenT, Zhang H, Wang J, et al. MCU-dependent mitochondrial Ca²⁺ inhibits NAD+/SIRT3/SOD2 pathway to promote ROS production and metastasis of HCC cells[J]. Oncogene, 2017, 36(42):5897-5909. doi: 10.1038/onc.2017.167 pmid: 28650465
[17]	Fu Q, Zhang Q, Lou Y, et al. Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer[J]. Oncogene, 2018, 37(47):6105-6118. doi: 10.1038/s41388-018-0391-0 URL
[18]	Zhou D, Luan J, Huang C, et al. Tumor-associated macrophages in hepatocellular carcinoma: friend or foe?[J]. Gut Liver, 2021, 15(4):500-516. doi: 10.5009/gnl20223 URL
[19]	Wang LP, Lin J, Ma XQ, et al. Exosomal DLX6-AS1 from hepatocellular carcinoma cells induces M2 macrophage polarization to promote migration and invasion in hepatocellular carcinoma through microRNA-15a-5p/CXCL17 axis[J]. J Exp Clin Cancer Res, 2021, 40(1):177. doi: 10.1186/s13046-021-01973-z URL
[20]	Halvorsen EC, Mahmoud SM, Bennewith KL. Emerging roles of regulatory T cells in tumour progression and metastasis[J]. Cancer Metastasis Rev, 2014, 33(4):1025-1041. doi: 10.1007/s10555-014-9529-x URL
[21]	Yang HD, Eun JW, Lee KB, et al. T-cell immune regulator 1 enhances metastasis in hepatocellular carcinoma[J]. Exp Mol Med, 2018, 50(1):e420. doi: 10.1038/emm.2017.166 URL
[22]	Chen S, Dong Z, Yang P, et al. Hepatitis B virus X protein stimulates high mobility group box 1 secretion and enhances hepatocellular carcinoma metastasis[J]. Cancer Lett, 2017, 394:22-32. doi: 10.1016/j.canlet.2017.02.011 URL
[23]	Duan L, Wu R, Zhang X, et al. HBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells[J]. Cell Death Dis, 2018, 9(6):629. doi: 10.1038/s41419-018-0512-2 URL
[24]	Liu LZ, Zhang Z, Zheng BH, et al. CCL15 recruits suppressive monocytes to facilitate immune escape and di-sease progression in hepatocellular carcinoma[J]. Hepato-logy, 2019, 69(1):143-159.
[25]	Wu S, Zheng Q, Xing X, et al. Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation[J]. J Exp Clin Cancer Res, 2018, 37(1):99. doi: 10.1186/s13046-018-0761-z URL
[26]	Liu Z, Mo H, Liu R, et al. Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression[J]. Cell Death Dis, 2021, 12(12):1134. doi: 10.1038/s41419-021-04418-9 URL
[27]	Peng JM, Lin SH, Yu MC, et al. CLIC1 recruits PIP5K1A/C to induce cell-matrix adhesions for tumor metastasis[J]. J Clin Invest, 2021, 131(1):e133525.
[28]	Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20):1894-1905. doi: 10.1056/NEJMoa1915745 URL
[29]	Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(26):2960-2970. doi: 10.1200/JCO.20.00808 URL
[30]	Hsu CY, Liu PH, Ho SY, et al. Metastasis in patients with hepatocellular carcinoma: prevalence, determinants, prognostic impact and ability to improve the barcelona clinic liver cancer system[J]. Liver Int, 2018, 38(10):1803-1811. doi: 10.1111/liv.13748 URL
[31]	Lee JI, Kim JK, Kim DY, et al. Prognosis of hepatocellular carcinoma patients with extrahepatic metastasis and the controllability of intrahepatic lesions[J]. Clin Exp Metastasis, 2014, 31(4):475-482. doi: 10.1007/s10585-014-9641-x URL
[32]	Jin YJ, Lee HC, Lee D, et al. Role of the routine use of chest computed tomography and bone scan in staging workup of hepatocellular carcinoma[J]. J Hepatol, 2012, 56(6):1324-1329. doi: 10.1016/j.jhep.2011.12.027 URL
[33]	Chu KKW, Chan ACY, Ma KW, et al. Role of C11-FDG dual-tracer PET-CT scan in metastatic screening of hepatocellular carcinoma-a cost-effectiveness analysis[J]. Hepatobiliary Surg Nutr, 2021, 10(3):301-307. doi: 10.21037/hbsn.2019.11.09 URL
[34]	MacMahon H, Naidich DP, Goo JM, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner society 2017[J]. Radiology, 2017, 284(1):228-243. doi: 10.1148/radiol.2017161659 pmid: 28240562
[35]	Kuo TM, Chang KM, Cheng TI, et al. Clinical factors predicting better survival outcome for pulmonary metastasectomy of hepatocellular carcinoma[J]. Liver Cancer, 2017, 6(4):297-306. doi: 10.1159/000477134 URL
[36]	Invenizzi F, Iavarone M, Donato MF, et al. Pulmonary resection for metastasis of hepatocellular carcinoma recurring after liver transplant: an Italian multicenter experience[J]. Front Oncol, 2020, 10:381. doi: 10.3389/fonc.2020.00381 pmid: 32351877
[37]	Hori A, Ohira R, Nakamura T, et al. Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma[J]. Br J Radiol, 2020, 93(1110):20190407.
[38]	Zuo T, Lin W, Liu F, et al. Artificial pneumothorax improves radiofrequency ablation of pulmonary metastases of hepatocellular carcinoma close to mediastinum[J]. BMC Cancer, 2021, 21(1):505. doi: 10.1186/s12885-021-08223-7 URL
[39]	Jiang W, Zeng ZC, Zhang JY, et al. Palliative radiation therapy for pulmonary metastases from hepatocellular carcinoma[J]. Clin Exp Metastasis, 2012, 29(3):197-205. doi: 10.1007/s10585-011-9442-4 URL