MET基因及其表达在卵巢癌中的研究进展与临床意义

doi:10.3760/cma.j.cn371439-20250727-00018

摘要/Abstract

摘要：

卵巢癌是女性生殖系统常见的恶性肿瘤，治疗难度大，预后较差。间质上皮转化因子（MET）基因及其编码的受体酪氨酸激酶c-MET在卵巢癌的发生、发展、转移和耐药过程中起着关键作用。研究表明，MET在卵巢癌中存在异常高表达或基因扩增，其表达水平与肿瘤亚型、分期、患者预后及治疗反应密切相关。c-MET及其下游信号通路的过度激活不仅促进肿瘤细胞的增殖、侵袭与转移，还参与化疗耐药机制。随着分子检测技术及分子靶向治疗的不断发展，MET已成为卵巢癌潜在的重要预后生物标志物和治疗靶点。系统阐述MET基因在卵巢癌中的表达特征、分型差异、功能机制及其临床意义，对其未来研究方向和临床应用前景具有重要的指导意义。

关键词: 卵巢肿瘤, 原癌基因蛋白质c-met, 基因扩增, 基因表达

Abstract:

Ovarian cancer is a common malignant tumor of the female reproductive system， which is difficult to treat and has a poor prognosis. The mesenchymal-epithelial transition factor （MET） gene and its encoded receptor tyrosine kinase c-MET play a critical role in the occurrence， development， metastasis and drug resistance of ovarian cancer. Studies have shown that MET is abnormally overexpressed or amplified in ovarian cancer， and its expression level is closely related to tumor subtype， stage， prognosis and treatment response. Overactivation of c-MET and its downstream signaling pathways not only promote tumor cell proliferation， invasion and metastasis， but also participate in the mechanisms of chemoresistance. As molecular detection technologies and targeted therapies continue to advance， MET is emerging as a significant prognostic biomarker and therapeutic target in ovarian cancer. Systematically expounding the expression characteristics， classification differences， functional mechanisms and clinical significance of the MET gene in ovarian cancer has important guiding significance for its future research directions and clinical application prospects.

Key words: Ovarian neoplasms, Proto-oncogene proteins c-met, Gene amplification, Gene expression

崔菲菲, 黄文亭. MET基因及其表达在卵巢癌中的研究进展与临床意义[J]. 国际肿瘤学杂志, 2026, 53(2): 115-119.

Cui Feifei, Huang Wenting. Research progress and clinical significance of MET gene and its expression in ovarian cancer[J]. Journal of International Oncology, 2026, 53(2): 115-119.

参考文献 40

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.
[2]	Zhang R, Shi H, Ren F, et al. Down-regulation of miR-338-3p and up-regulation of MACC1 indicated poor prognosis of epithelial ovarian cancer patients[J]. J Cancer, 2019, 10(6): 1385-1392. DOI: 10.7150/jca.29502. pmid: 31031848
[3]	郭斌生, 徐寒梅, 欧瑜. 靶向HGF/c-Met信号通路的抗体类抗肿瘤药物研究进展[J]. 药物生物技术, 2017, 24(6): 534-540. DOI: 10.19526/j.cnki.1005-8915.20170615.
[4]	Kim WY, Shim SH, Jung HY, et al. The gene copy number of c-MET has a significant impact on progression-free survival in Korean patients with ovarian carcinoma[J]. Hum Pathol, 2017, 64: 98-105. DOI: 10.1016/j.humpath.2017.04.002. pmid: 28428108
[5]	Wang J, Cheng JX. c-Met inhibition enhances chemosensitivity of human ovarian cancer cells[J]. Clin Exp Pharmacol Physiol, 2017, 44(1): 79-87. DOI: 10.1111/1440-1681.12672.
[6]	Kwon JE, Jang Y, Yun BS, et al. Met overexpression in ovarian cancer via CD24-induced downregulation of miR-181a: a signalling for cellular quiescence-like state and chemoresistance in ovarian CSCs[J]. Cell Prolif, 2024, 57(5): e13582. DOI: 10.1111/cpr.13582.
[7]	Bååth M, Jönsson JM, Westbom Fremer S, et al. MET expression and cancer stem cell networks impact outcome in high-grade serous ovarian cancer[J]. Genes (Basel), 2021, 12(5): 742. DOI: 10.3390/genes12050742.
[8]	Pan X, Chen Y, Gao S. Four genes relevant to pathological grade and prognosis in ovarian cancer[J]. Cancer Biomark, 2020, 29(2): 169-178. DOI: 10.3233/cbm-191162.
[9]	Lim L, Wu CC, Hsu YT, et al. Clinical significance of c-Met and phospho-c-Met (Tyr1234/1235) in ovarian cancer[J]. Taiwan J Obstet Gynecol, 2019, 58(1): 105-110. DOI: 10.1016/j.tjog.2018.11.020. pmid: 30638462
[10]	Kim HS, Chon HJ, Kim H, et al. MET in gastric cancer with liver metastasis: the relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis[J]. J Surg Oncol, 2018, 117(8): 1679-1686. DOI: 10.1002/jso.25097. pmid: 29790169
[11]	Liu XW, Chen XR, Rong YM, et al. MET exon 14 skipping mutation, amplification and overexpression in pulmonary sarcomatoid carcinoma: a multi-center study[J]. Transl Oncol, 2020, 13(12): 100868. DOI: 10.1016/j.tranon.2020.100868.
[12]	Kim JH, Jang HJ, Kim HS, et al. Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis[J]. J Cancer, 2018, 9(19): 3427-3434. DOI: 10.7150/jca.26071. pmid: 30310499
[13]	Zhou HY, Pon YL, Wong AS. HGF/MET signaling in ovarian cancer[J]. Curr Mol Med, 2008, 8(6): 469-480. DOI: 10.2174/15665 2408785747933. doi: 10.2174/156652408785747933 pmid: 18781954
[14]	Wang H, Tan M, Zhang S, et al. Expression and significance of CD44, CD47 and c-met in ovarian clear cell carcinoma[J]. Int J Mol Sci, 2015, 16(2): 3391-3404. DOI: 10.3390/ijms16023391. pmid: 25658794
[15]	Orian-Rousseau V, Morrison H, Matzke A, et al. Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin[J]. Mol Biol Cell, 2007, 18(1): 76-83. DOI: 10.1091/mbc.e06-08-0674. pmid: 17065554
[16]	Kenda Suster N, Virant-Klun I. Presence and role of stem cells in ovarian cancer[J]. World J Stem Cells, 2019, 11(7): 383-397. DOI: 10.4252/wjsc.v11.i7.383. pmid: 31396367
[17]	张瑞涛, 任芳, 史惠蓉. 不同期别卵巢上皮性癌组织中结肠癌转移相关基因1表达[J]. 中国医学科学院学报, 2014, 36(1): 47-51. DOI: 10.3881/j.issn.1000-503X.2014.01.009.
[18]	Li H, Zhang H, Zhao S, et al. Overexpression of MACC1 and the association with hepatocyte growth factor/c-Met in epithelial ovarian cancer[J]. Oncol Lett, 2015, 9(5): 1989-1996. DOI: 10.3892/ol.2015.2984. pmid: 26137000
[19]	Yang S, Li Z, Luo R. miR-34c targets MET to improve the anti-tumor effect of cisplatin on ovarian cancer[J]. Onco Targets Ther, 2020, 13: 2887-2897. DOI: 10.2147/ott.S239425.
[20]	Xu F, Ni M, Li J, et al. Circ0004390 promotes cell proliferation through sponging miR-198 in ovarian cancer[J]. Biochem Biophys Res Commun, 2020, 526(1): 14-20. DOI: 10.1016/j.bbrc.2020.03.024.
[21]	Zhang J, Wang Z, Zhang S, et al. Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER[J]. Cell Signal, 2018, 50: 100-110. DOI: 10.1016/j.cellsig.2018.06.006. pmid: 29920310
[22]	Morgan RD, Ferreras C, Peset I, et al. c-MET/VEGFR-2 co-localisa-tion impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial[J]. BMC Med, 2022, 20(1): 59. DOI: 10.1186/s12916-022-02270-y.
[23]	Wong AS, Pelech SL, Woo MM, et al. Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis?[J]. Onco-gene, 2001, 20(11): 1318-1328. DOI: 10.1038/sj.onc.1204253.
[24]	Sawada K, Radjabi AR, Shinomiya N, et al. c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion[J]. Cancer Res, 2007, 67(4): 1670-1679. DOI: 10.1158/0008-5472.CAN-06-1147. pmid: 17308108
[25]	Wong AST, Roskelley CD, Pelech S, et al. Progressive changes in Met-dependent signaling in a human ovarian surface epithelial model of malignant transformation[J]. Exp Cell Res, 2004, 299(1): 248-256. DOI: 10.1016/j.yexcr.2004.06.002. pmid: 15302591
[26]	Li QJ, Wu ZL, Wang J, et al. An EMT-based gene signature enhances the clinical understanding and prognostic prediction of patients with ovarian cancers[J]. J Ovarian Res, 2023, 16(1): 51. DOI: 10.1186/s13048-023-01132-2.
[27]	Dai C, Xie Y, Zhuang X, et al. MiR-206 inhibits epithelial ovarian cancer cells growth and invasion via blocking c-Met/AKT/mTOR signaling pathway[J]. Biomed Pharmacother, 2018, 104: 763-770. DOI: 10.1016/j.biopha.2018.05.077. pmid: 29807226
[28]	Yin B, Ding J, Liu J, et al. Exosomal CMTM4 induces immunosuppressive macrophages to promote ovarian cancer progression and attenuate anti-PD-1 immunotherapy[J]. Adv Sci (Weinh), 2025, 12(30): e04436. DOI: 10.1002/advs.202504436.
[29]	Sun H, Huo X, Bi X, et al. Exosome transmit the ability of migration and invasion in heterogeneous ovarian cancer cells by regulating autophagy via targeting hsa-miR-328[J]. Gynecol Oncol, 2025, 194: 60-70. DOI: 10.1016/j.ygyno.2025.02.011. pmid: 39970632
[30]	Nwani NG, Sima LE, Nieves-Neira W, et al. Targeting the microenvironment in high grade serous ovarian cancer[J]. Cancers (Basel), 2018, 10(8): 266. DOI: 10.3390/cancers10080266.
[31]	Nakatani M, Watari H, Mitamura T, et al. The anti-tumor effect of cabozantinib on ovarian clear cell carcinoma in vitro and in vivo[J]. Anticancer Res, 2017, 37(11): 6125-6132. DOI: 10.21873/anticanres.12061. pmid: 29061793
[32]	Xu XB, Li NS, Wang H, et al. Expression and prognostic significance of the DNA damage response pathway and autophagy markers in gastric cancer[J]. Neoplasma, 2021, 68(6): 1310-1319. DOI: 10.4149/neo_2021_210515N667.
[33]	郑建华, 罗虹, 曲丹妮, 等. 卵巢肿瘤组织中c-met蛋白表达的意义[J]. 中国实用妇科与产科杂志, 2002, 18(11): 681-682. DOI: 10.3969/j.issn.1005-2216.2002.11.020.
[34]	Yamamoto S, Tsuda H, Miyai K, et al. Gene amplification and protein overexpression of Met are common events in ovarian clear-cell adenocarcinoma: their roles in tumor progression and prognostication of the patient[J]. Mod Pathol, 2011, 24(8): 1146-1155. DOI: 10.1038/modpathol.2011.70.
[35]	王慧敏, 谭明子, 张嵩, 等. CD44、CD47和c-met在卵巢透明细胞癌中的表达及意义[J]. 中国医学科学院学报, 2016, 38(6): 720-725. DOI: 10.3881/j.issn.1000-503X.2016.06.016.
[36]	Puvanenthiran S, Essapen S, Haagsma B, et al. Co-expression and prognostic significance of the HER family members, EGFRvⅢ, c-MET, CD44 in patients with ovarian cancer[J]. Oncotarget, 2018, 9(28): 19662-19674. DOI: 10.18632/oncotarget.24791. pmid: 29731973
[37]	Zhang L, Zhang X, Fan S, et al. Identification of modules and hub genes associated with platinum-based chemotherapy resistance and treatment response in ovarian cancer by weighted gene co-expression network analysis[J]. Medicine (Baltimore), 2019, 98(44): e17803. DOI: 10.1097/md.0000000000017803.
[38]	Gu Y, Zhang S. A five-gene expression signature predicts ovarian cancer metastasis[J]. Crit Rev Eukaryot Gene Expr, 2021, 31(5): 41-50. DOI: 10.1615/CritRevEukaryotGeneExpr.2021039014.
[39]	Zhao B, Pei L. A macrophage related signature for predicting prognosis and drug sensitivity in ovarian cancer based on integrative machine learning[J]. BMC Med Genomics, 2023, 16(1): 230. DOI: 10.1186/s12920-023-01671-z.
[40]	Zhang L, Sun W, Ren W, et al. Predicting panel of metabolism and immune-related genes for the prognosis of human ovarian cancer[J]. Front Cell Dev Biol, 2021, 9: 690542. DOI: 10.3389/fcell.2021.690542.