冯春草,李富娟

在全球范围内，女性生殖系统疾病严重威胁着女性健康，其中卵巢癌（Ovarian Cancer，OC）是一种发病率较高且死亡率较高的常见的妇科恶性肿瘤。由于缺少高效的筛查和确诊手段，卵巢癌在早期往往难以被发现，许多患者在被确诊时已经进入了局部或远处转移状态[1]。流行病学调查和对肿瘤发病机制的研究显示，卵巢癌的患病率随时间推移逐渐增加。随着社会发展和医疗水平提高，卵巢癌患者的年龄朝着年轻化发展，发病率也持续上升[2]。卵巢癌对女性的身心健康和生活质量构成了严重威胁，因此，探索并确立用于卵巢癌早期诊断的特异性生物标志物显得尤为迫切和必要。近年来，肿瘤干细胞学说在肿瘤学领域引发了广泛关注依据这一学说，肿瘤干细胞作为肿瘤恶性行为的关键来源，不但开启了肿瘤生长进程，而且对于放疗和化疗展现出较强的抗性，故而被视为肿瘤复发和转移的根源所在[3]。肿瘤干细胞与普通细胞存在诸多相似之处，像自我更新和多向分化能力便是二者共有的特性。在卵巢癌以及多种其他癌症中，肿瘤干细胞以具有干性特征的小群体细胞形式存在，发挥着重要作用。因此，针对肿瘤干细胞的靶向治疗已成为当前卵巢癌的研究的重要方向之一。

上皮性卵巢癌；SFRP2；DDX4

[1] Siegel,Miller,Fuchs,et al.Cancer statistics,2022[J].CA:A Cancer Journal for Clinicians,2022,72(1):7-33. [2] 周先荣.2014年WHO卵巢上皮性肿瘤分类解读[J].实用妇产科杂志,2017,33(11):801-803. [3] Clarke MF,Dick JE,Dirks PB,et al.Cancer stem cells--perspectives on current status and future directions:AACRWorkshop on cancer stem cells[J].Cancer Res,2006,66(19):9339. [4] 卢淮武,叶栋栋,吴斌等.《2023NCCN卵巢癌包括输卵管癌及原发性腹膜癌临床实践指南(第1版)》解读[J].中国实用妇科与产科杂志,2023,39(01):58-67. [5] Arora T,Mullangi S,Vadakekut ES,Lekkala MR.Epithelial Ovarian Cancer.2024 May 6.In:StatPearls[Internet].Treasure Island(FL): StatPearls Publishing;2025 Jan-.PMID:33620837. [6] 李永坤,王道荣.分泌型卷曲相关蛋白基因甲基化与大肠癌的研究进展[J].肿瘤研究与临床,2010(12):862-864. [7] 裴磊,叶丽平.Wnt抑制因子SFRP基因甲基化与白血病的关系[J].山东医药,2011,51(33):109-111. [8] 李永坤.外周血中SFRP2基因超甲基化改变与大肠癌发生､发展的初步研究[D].扬州:扬州大学,2012. [9] 肖灿.SFRP2基因甲基化促进口腔粘膜鳞癌发生的分子机制研究[D].苏州:苏州大学,2013. [10] FUKUI T,KONDO M,ITO G,et al.Transcriptional silencing of secreted frizzled related protein 1(SFRP 1)by promoter hypermeth- ylation in non-small-cell lung cancer[J].Oncogene,2005,24(41):6323-6327. [11] VINCENT K M,POSTOVIT L M.Matricellular proteins in cancer:A focus on secreted Frizzled-related proteins[J].J Cell Commun Signal,2018,12(1):103-112. [12] GARCÍA-TOBILLA P,SOLÓRZANO SR,SALIDO-GUADARRAMA I,et al.SFRP1 repression in prostate cancer is triggered by two different epigenetic mechanisms[J].Gene,2016,30;593(2):292-301. [13] HU H,WANG T,PANR,et al.Hypermethylated promoters of secreted frizzled-related protein genes are associated with colorectal cancer[J].Pathol OncolRes,2019,25(2):567-575. [14] Chang J T,Esumi N,Moore K,et al.Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium[J].Hum Mol Genet,1999,8(4):575-83. [15] Kawano Y,Kypta R.Secreted antagonists of the Wnt signalling pathway[J].J Cell Sci,2003,116(Pt 13):2627-2634. [16] Rattner A,Hsieh J C,Smallwood P M,et al.A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors[J].Proc Natl Acad Sci U S A,1997,94(7):2859-2863. [17] Lin K,Wang S,Julius M A,et al.The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling[J].Proc Natl Acad Sci U S A,1997,94(21):11196-200. [18] Li C,Chen H,Hu L,et al.Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2[J].BMC Mol Biol,2008,9:11. [19] Teng Y,Wang X,Wang Y,et al.Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells[J].Biochem Biophys Res Commun,2010,392(3):373-379. [20] Stewart D J.Wnt signaling pathway in non-small cell lung cancer[J].J Natl Cancer Inst,2014,106(1):djt356. [21] Mazieres J,He B,You L,et al.Wnt signaling in lung cancer[J].Cancer Lett,2005,222(1):1-10. [22] Xue Y,Chen C,Xu W,Xu H,Zheng J,Gu Y.Downregulation of Frizzled-7 induces the apoptosis of hepatocellular carcinoma cells through inhibition of NF-κB.Oncol Lett.2018 May;15(5):7693-7701. [23] M.Hsieh,M.A.Johnson,N.M.Greenberg,J.S.Richards Regulated expression of wnts and frizzleds at specific stages of follicular development in the rodent ovary Endocrinology,143(2002),pp.898-908 27 [24] A.Boyer,A.K.Goff,D.Boerboom WNT signaling in ovarian follicle biology and tumorigenesisTrends Endocrinol.Metab., 21(2010), pp.25-32. [25] D.Boerboom,M.Paquet,M.Hsieh,J.Liu,S.P.Jamin,R.R.Behringer,J.Sirois,M.M.Taketo,J.S.Richards Misregulated Wnt/β-catenin signa- ling leads to ovarian granulosa cell tumor development Cancer Res.,65(2005),pp.9206-9215. [26] Zhang X,Rong X,Chen Y,Su L.Methylation-mediated loss of SFRP2 enhances invasiveness of non-small cell lung cancer cells.Hum Exp Toxicol.2018 Feb;37(2):155-162. [27] Wen X,Zhang S,Zhang Y.[Research progress in DEAD-box family protein in cancer].Zhong Nan Da Xue Xue Bao Yi Xue Ban.2017 Nov 28;42(11):1311-1315.Chinese. [28]Yang Q,Huang T,Ye G,Wang B,Zhang X.Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis:a systematic meta-analysis.Sci Rep.2016 Sep 23;6:33339. [29] Lee AY,He B,You L,Dadfarmay S,Xu Z,Mazieres J,Mikami I,McCormick F,Jablons DM.Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma.Oncogene.2004 Aug 26;23(39):6672-6. [30] Yu J,Xie Y,Li M,Zhou F,Zhong Z,Liu Y,Wang F,Qi J.Association between SFRP promoter hypermethylation and different types of cancer:A systematic review and meta-analysis.Oncol Lett.2019 Oct;18(4):3481-3492. [31] Zhang T,Ma Z,Liu L,Sun J,Tang H,Zhang B,Zou Y,Li H.DDX39 promotes hepatocellular carcinoma growth and metastasis through activating Wnt/β-catenin pathway.Cell Death Dis.2018 Jun 4;9(6):675. [32] Raz E.The function and regulation of vasa-like genes in germ-cell development.Genome Biol.2000;1(3):REVIEWS1017. [33] Stimpfel M,Skutella T,Cvjeticanin B,Meznaric M,Dovc P,Novakovic S,Cerkovnik P,Vrtacnik-Bokal E,Virant-Klun I.Isolation, characterization and differentiation of cells expressing pluripotent/multipotent markers from adult human ovaries.Cell Tissue Res.2013 Nov;354(2):593-607. [34] White YA,Woods DC,Takai Y,Ishihara O,Seki H,Tilly JL.Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women.Nat Med.2012 Feb 26;18(3):413-21. [35] Dunlop CE,Telfer EE,Anderson RA.Ovarian stem cells--potential roles in infertility treatment and fertility preservation.Maturitas.2013 Nov;76(3):279-83.

点击下载PDF