Research progress on molecular mechanism and treatment of liver metastasis in gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Xian , NI Yongjun ,  LÜ Chengyu

1. Department of General Surgery, Nanjing First Hospital, Nanjing 210001, P. R. China;

Corresponding author：

LÜ Chengyu, Email: lcy_1234@aliyun.com

Keywords：

gastric cancer with liver metastasis; non-coding RNA; circulating tumor cell; exosome; tumor microenvironment; signal pathway; treatment

DOI：

10.7507/1007-9424.202308064

Video：

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Objective To summarize the molecular mechanisms and clinical treatment of gastric cancer with liver metastasis (GCLM), in order to provide new ideas for future treatment. Method The literatures about mechanism and treatment strategy of GCLM in recent years were searched and reviewed. Results Most patients with gastric cancer were in advanced stage or had developed distant metastases when they were first diagnosed, among which liver was the common site of metastasis. The complex molecular mechanisms of GCLM had not been fully clarified. Molecular mechanisms at different levels, including non-coding RNA, circulating tumor cells, exosomes, tumor microenvironment and signaling pathways, were relatively independent and interacted with each other, providing potential biomarkers and therapeutic targets for GCLM. At present, the best treatment method for patients with GCLM was mainly divided into local and systemic treatment. The local treatment included surgical treatment, radiofrequency ablation and proton beam therapy, while the systemic treatment included systemic chemotherapy, targeted therapy and immunotherapy, among which the targeted therapy and immunotherapy were the focus of recent research. Conclusions The mechanism of GCLM is the result of the interaction between tumor cells and the microenvironment at the site of metastasis. Understanding them is of great significance to guide clinical treatment and prognosis. At present, there is no unified treatment standard for GCLM. To achieve the ideal treatment effect, we should not only rely on single therapy, but also adopt multi-disciplinary and individual therapy according to the specific disease status of patients and the nature of tumors.

Citation： LI Xian, NI Yongjun, LÜ Chengyu. Research progress on molecular mechanism and treatment of liver metastasis in gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(1): 115-122. doi: 10.7507/1007-9424.202308064 Copy

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9. Gialeli C, Gungor B, Blom AM. Novel potential inhibitors of complement system and their roles in complement regulation and beyond. Mol Immunol, 2018, 102: 73-83.
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11. Xie T, Wu D, Li S, et al. microRNA-582 potentiates liver and lung metastasis of gastric carcinoma cells through the FOXO3-Mediated PI3K/Akt/Snail pathway. Cancer Manag Res, 2020, 12: 5201-5212.
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13. Yao J, Deng B, Zheng L, et al. miR-27b is upregulated in cervical carcinogenesis and promotes cell growth and invasion by regulating CDH11 and epithelial-mesenchymal transition. Oncol Rep, 2016, 35(3): 1645-1651.
14. Feng Q, Wu X, Li F, et al. miR-27b inhibits gastric cancer metastasis by targeting NR2F2. Protein Cell, 2017, 8(2): 114-122.
15. Nishida N, Mimori K, Fabbri M, et al. MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res, 2011, 17(9): 2725-2733.
16. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376(9742): 687-697.
17. Hashiguchi Y, Nishida N, Mimori K, et al. Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance. Int J Oncol, 2012, 40(5): 1477-1482.
18. Wang Z, Yao L, Li Y, et al. miR-337-3p inhibits gastric tumor metastasis by targeting ARHGAP10. Mol Med Rep, 2020, 21(2): 705-719.
19. Tam C, Wong JH, Tsui SKW, et al. LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years. Appl Microbiol Biotechnol, 2019, 103(12): 4649-4677.
20. Zhuo W, Liu Y, Li S, et al. Long noncoding RNA GMAN, up-regulated in gastric cancer tissues, is associated with metastasis in patients and promotes translation of Ephrin A1 by competitively binding GMAN-AS. Gastroenterology, 2019, 156(3): 676-691. e11. doi: 10.1053/j.gastro.2018.10.054.
21. Ba MC, Ba Z, Long H, et al. LncRNA AC0938181. Accelerates gastric cancer metastasis by epigenetically promoting PDK1 expression. Cell Death Dis, 2020, 11(1): 64.
22. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol, 2015, 12(4): 381-388.
23. Chen B, Huang S. Circular RNA: an emerging non-coding RNA as a regulator and biomarker in cancer. Cancer Lett, 2018, 418: 41-50.
24. Zhang J, Hou L, Liang R, et al. CircDLST promotes the tumorigenesis and metastasis of gastric cancer by sponging miR-502-5p and activating the NRAS/MEK1/ERK1/2 signaling. Mol Cancer, 2019, 18(1): 80. doi: 10.1186/s12943-019-1015-1.
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26. Lee MW, Kim GH, Jeon HK, et al. Clinical application of circulating tumor cells in gastric cancer. Gut Liver, 2019, 13(4): 394-401.
27. Huang X, Gao P, Sun J, et al. Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: a meta-analysis. Int J Cancer, 2015, 136(1): 21-33.
28. Hüsemann Y, Geigl JB, Schubert F, et al. Systemic spread is an early step in breast cancer. Cancer Cell, 2008, 13(1): 58-68.
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31. Zhang Y, Liu D, Chen X, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell, 2010, 39(1): 133-144.
32. Zhang H, Deng T, Liu R, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun, 2017, 8: 15016. doi: 10.1038/ncomms15016.
33. Alderton GK. Metastasis. Exosomes drive premetastatic niche formation. Nat Rev Cancer, 2012, 12(7): 447. doi: 10.1038/nrc3304.
34. Qiu S, Xie L, Lu C, et al. Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis. J Exp Clin Cancer Res, 2022, 41(1): 296. doi: 10.1186/s13046-022-02499-8.
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36. Zhang Y, Han T, Feng D, et al. Screening of non-invasive miRNA biomarker candidates for metastasis of gastric cancer by small RNA sequencing of plasma exosomes. Carcinogenesis, 2020, 41(5): 582-590.
37. Kwa MQ, Herum KM, Brakebusch C. Cancer-associated fibroblasts: how do they contribute to metastasis? Clin Exp Metastasis, 2019, 36(2): 71-86.
38. Curtis M, Kenny HA, Ashcroft B, et al. Fibroblasts mobilize tumor cell glycogen to promote proliferation and metastasis. Cell Metab, 2019, 29(1): 141-155. e9.
39. Luo Q, Wang CQ, Yang LY, et al. FOXQ1/NDRG1 axis exacerbates hepatocellular carcinoma initiation via enhancing crosstalk between fibroblasts and tumor cells. Cancer Lett, 2018, 417: 21-34.
40. Li Q, Zhu CC, Ni B, et al. Lysyl oxidase promotes liver metastasis of gastric cancer via facilitating the reciprocal interactions between tumor cells and cancer associated fibroblasts. EBioMedicine, 2019, 49: 157-171.
41. Zhao Z, Zhang Y, Guo E, et al. Periostin secreted from podoplanin-positive cancer-associated fibroblasts promotes metastasis of gastric cancer by regulating cancer stem cells via AKT and YAP signaling pathway. Mol Carcinog, 2023, 62(5): 685-699.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on molecular mechanism and treatment of liver metastasis in gastric cancer

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