血清肿瘤标志物在卵巢癌诊断中的研究进展

郭钰; 徐鹏; 王蓓蒂; 李栗扬; 高爽; 匡野

doi:10.16766/j.cnki.issn.1674-4152.002061

血清肿瘤标志物在卵巢癌诊断中的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.002061

哈尔滨医科大学附属第二医院妇产科，黑龙江哈尔滨 150086

基金项目:

吴阶平医学基金会临床科研课题项目 320675018061

详细信息

通讯作者:
匡野, E-mail: kuangye-blue@163.com

中图分类号: R737.31 R730.43
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- 文章访问数: 156
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- 被引次数: 0
出版历程
- 收稿日期: 2021-01-05
- 网络出版日期: 2022-02-16

The research progress of serum tumor markers in the diagnosis of ovarian cancer

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China

摘要

摘要: 卵巢癌(ovarian cancer，OC)是全球三大妇科恶性肿瘤之一，其早期症状隐匿，缺乏有效的临床筛查手段，病死率较高，预后较差。尽可能早期发现疾病已成为近年来临床和科研工作的焦点。经阴道超声联合生物标志物检测是现阶段临床最常见的癌症筛查策略。癌胚抗原125(cancer antigen 125，CA125)是一种高分子量、高度糖基化的跨膜黏蛋白糖蛋白，可通过免疫测定法直接测定血清浓度，是目前临床应用最广泛的传统蛋白质肿瘤标志物之一，但缺乏足够的灵敏度和特异性。目前，对新诊断靶标的探索十分迫切，包括循环肿瘤DNA(circulating tumor DNA，ctDNA)、微小RNA(microRNA，miRNA)和环状RNA(circular RNA，circRNA)等在内的诸多新兴肿瘤标志物正引起科研工作者的广泛关注，肿瘤标志物的联合检测具有重要的临床意义。对新兴肿瘤标志物的深入研究不仅有利于对疾病的早期诊断、早期治疗，还有助于推动对卵巢癌增殖、侵袭、转移、耐药等机制的进一步探索与思考。本文旨在综述近年来在卵巢癌诊断方面具有潜力的血清肿瘤标志物的研究进展，以期为卵巢癌早期诊断提供帮助，提高临床检出率，改善卵巢癌患者预后。
- 卵巢癌 /
- 诊断 /
- 肿瘤标志物
Abstract: Ovarian cancer (OC) is one of the three gynecological malignancies in the world. Due to the lack of obvious clinical symptoms and effective screening methods in early OC, the patients have a high fatality rate, and their prognosis is poor. In recent years, early detection of OC is the hot spot of research for the clinical and scientific research workers. Transvaginal ultrasound combined with biomarker detection is the most common screening strategy at now. Cancer antigen 125 (CA125) is a high molecular weight, highly glycosylated transmembrane mucin glycoprotein, which can be directly determined by immunoassay. It is currently the most widely used tumor protein marker, but the serology diagnosis for CA125 is lacking of sensitivity and specificity. At present, the exploration of new diagnostic targets is very urgent. Many serum tumor markers, including circulating tumor DNA (ctDNA), microRNA (miRNA) and circular RNA (circRNA), are attracting extensive attention of researchers. The combined detection of serum tumor markers has an important clinical significance. In-depth research on emerging tumor markers is not only conducive to early diagnosis and early treatment of OC, but help to promote the further exploration of mechanisms such as proliferation, invasion, metastasis, and drug resistance. This article aims to review the research progress of serum tumor markers with potential in the diagnosis of OC in recent years, in order to provide help for the early diagnosis of OC, increase the clinical detection rate, and improve the prognosis of patients.
- Ovarian cancer /
- Diagnosis /
- Tumor markers

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参考文献(47)

[1]	郎景和. 妇科恶性肿瘤筛查[J]. 中国实用妇科与产科杂志, 2016, 32(5): 385-389. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF201605001.htm
[2]	TORRE L A, TRABERT B, DESANTIS C E, et al. Ovarian cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(4): 284-296. doi: 10.3322/caac.21456
[3]	GUADAGNO E, PIGNATIELLO S, BORRELLI G, et al. Ovarian borderline tumors, a subtype of neoplasm with controversial behavior. Role of Ki67 as a prognostic factor[J]. Pathol Res Pract, 2019, 215(11): 152633. DOI: 10.1016/j.prp.2019.152633.
[4]	GIAMPAOLINO P, DELLA CORTE L, FORESTE V, et al. Unraveling a difficult diagnosis: The tricks for early recognition of ovarian cancer[J]. Minerva Med, 2019, 110(4): 279-291. http://www.researchgate.net/publication/333984344_Unraveling_a_difficult_diagnosis_the_tricks_for_early_recognition_of_ovarian_cancer
[5]	GUELI ALLETTI S, CAPOZZI V A, ROSATI A, et al. Laparoscopy vs. laparotomy for advanced ovarian cancer: A systematic review of the literature[J]. Minerva Med, 2019, 110(4): 341-357. http://www.researchgate.net/publication/334252526_Laparoscopy_vs_laparotomy_for_advanced_ovarian_cancer_a_systematic_review_of_the_literature
[6]	CHIOFALO B, BRUNI S, CERTELLI C, et al. Primary debulking surgery vs. interval debulking surgery for advanced ovarian cancer: Review of the literature and meta-analysis[J]. Minerva Med, 2019, 110(4): 330-340. http://www.researchgate.net/publication/334255809_Primary_debulking_surgery_vs_Interval_debulking_surgery_for_advanced_ovarian_cancer_Review_of_the_literature_and_meta-analysis
[7]	许艳, 徐灵, 索永刚, 等. 超声造影联合血清CA125、CA199、CEA对卵巢良恶性肿瘤的诊断价值[J]. 海南医学, 2020, 31(12): 1574-1576. doi: 10.3969/j.issn.1003-6350.2020.12.023
[8]	SHA R, BADHULIKA S. Recent advancements in fabrication of nanomaterial based biosensors for diagnosis of ovarian cancer: A comprehensive review[J]. Mikrochim Acta, 2020, 187(3): 181. doi: 10.1007/s00604-020-4152-8
[9]	JACOBS I J, MENON U, RYAN A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial[J]. Lancet, 2016, 387(10022): 945-956. doi: 10.1016/S0140-6736(15)01224-6
[10]	BLYUSS O, BURNELL M, RYAN A, et al. Comparison of Longitudinal CA125 algorithms as a first-line screen for ovarian cancer in the General Population[J]. Clin Cancer Res, 2018, 24(19): 4726-4733. doi: 10.1158/1078-0432.CCR-18-0208
[11]	TERRY K L, SCHOCK H, FORTNER R T, et al. A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort[J]. Clin Cancer Res, 2016, 22(18): 4664-4675. doi: 10.1158/1078-0432.CCR-16-0316
[12]	GRAYSON K, GREGORY E, KHAN G, et al. Urine Biomarkers for the early detection of ovarian cancer-are we there yet?[J]. Biomark Cancer, 2019, 11: 1179299X19830977. http://www.ncbi.nlm.nih.gov/pubmed/30833816
[13]	ASLAN K, ONAN M A, YILMAZ C, et al. Comparison of HE 4, CA 125, ROMA score and ultrasound score in the differential diagnosis of ovarian masses[J]. J Gynecol Obstet Hum Reprod, 2020, 49(5): 101713. doi: 10.1016/j.jogoh.2020.101713
[14]	LI B X, PU K, GE L, et al. Diagnostic significance assessment of the circulating cell-free DNA in ovarian cancer: An updated meta-analysis[J]. Gene, 2019, 714: 143993. doi: 10.1016/j.gene.2019.143993
[15]	刘毓, 刘斌, 倾丽梅, 等. 循环肿瘤DNA在卵巢癌的应用进展[J]. 国际妇产科学杂志, 2019, 46(6): 688-692. doi: 10.3969/j.issn.1674-1870.2019.06.021
[16]	王东营, 吴飞, 张炜旸, 等. 循环肿瘤DNA在上皮性卵巢癌诊断及预后评估中的应用[J]. 中华全科医师杂志, 2018, 17(12): 1033-1037. doi: 10.3760/cma.j.issn.1671-7368.2018.12.021
[17]	ARILDSEN N S, MARTIN DE LA FUENTE L, MÅSBÄCK A, et al. Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method[J]. Sci Rep, 2019, 9(1): 15506. doi: 10.1038/s41598-019-51697-6
[18]	TESTA U, PELOSI E, CASTELLI G. Colorectal cancer: Genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells[J]. Med Sci(Basel), 2018, 6(2): 31. http://www.mdpi.com/2076-3271/6/2/31/pdf
[19]	WEISS A S, SWISHER E, PENNINGTON K P, et al. Inherited mutations in fallopian tube, ovarian and primary peritoneal carcinoma: Changes in diagnoses and mutational frequency over 20 years[J]. Gynecol Oncol, 2020, 159(1): 214-220. doi: 10.1016/j.ygyno.2020.06.509
[20]	MORIKAWA A, HAYASHI T, SHIMIZU M, et al. PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma[J]. Oncotarget, 2018, 9(20): 15266-15274. doi: 10.18632/oncotarget.24555
[21]	OGASAWARA A, HIHARA T, YABUNO A, et al. Evaluation of circulating tumor DNA in patients with ovarian cancer harboring somatic PIK3CA or KRAS mutations[J]. Cancer Res Treat, 2020, 52(4): 1219-1228. http://www.researchgate.net/publication/341191336_Evaluation_of_Circulating_Tumor_DNA_in_Patients_with_Ovarian_Cancer_Harboring_Somatic_PIK3CA_or_KRAS_Mutations
[22]	WEIGELT B, COMINO-MÉNDEZ I, DE BRUIJN I, et al. Diverse BRCA1 and BRCA2 reversion mutations in circulating cell-free DNA of therapy-resistant breast or ovarian cancer[J]. Clin Cancer Res, 2017, 23(21): 6708-6720. doi: 10.1158/1078-0432.CCR-17-0544
[23]	KILLOCK D. Cancer SEEK and destroy a blood test for early cancer detection[J]. Nat Rev Clin Oncol, 2018, 15(6378): 133. http://smartsearch.nstl.gov.cn/paper_detail.html?id=eac87a40bd49dc089a0b2832682f49dd
[24]	HU Y B, ULRICH B C, SUPPLEE J, et al. False-positive plasma genotyping due to clonal hematopoiesis[J]. Clin Cancer Res, 2018, 24(18): 4437-4443. doi: 10.1158/1078-0432.CCR-18-0143
[25]	ABOUTALEBI H, BAHRAMI A, SOLEIMANI A, et al. The diagnostic, prognostic and therapeutic potential of circulating microRNAs in ovarian cancer[J]. Int J Biochem Cell Biol, 2020, 124: 105765. DOI: 10.1016/j.biocel.2020.105765.
[26]	FENG Y W, HANG W Z, SANG Z Y, et al. Identification of exosomal and non exosomal microRNAs associated with the drug resistance of ovarian cancer[J]. Mol Med Rep, 2019, 19(5): 3376-3392. http://www.onacademic.com/detail/journal_1000042324685099_c12b.html
[27]	CHEN M W, YANG S T, CHIEN M H, et al. The STAT3-miRNA-92-Wnt signaling pathway regulates spheroid formation and malignant progression in ovarian cancer[J]. Cancer Res, 2017, 77(8): 1955-1967. doi: 10.1158/0008-5472.CAN-16-1115
[28]	DUAN S F, DONG X C, HAI J, et al. MicroRNA-135a-3p is downregulated and serves as a tumour suppressor in ovarian cancer by targeting CCR2[J]. Biomed Pharmacother, 2018, 107: 712-720. doi: 10.1016/j.biopha.2018.08.044
[29]	DONG P X, XIONG Y, WATARI H, et al. MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells[J]. J Exp Clin Cancer Res, 2016, 35(1): 132. doi: 10.1186/s13046-016-0415-y
[30]	EOH K J, LEE S H, KIM H J, et al. MicroRNA-630 inhibitor sensitizes chemoresistant ovarian cancer to chemotherapy by enhancing apoptosis[J]. Biochem Biophys Res Commun, 2018, 497(2): 513-520. doi: 10.1016/j.bbrc.2018.02.062
[31]	YOKOI A, YOSHIOKA Y, HIRAKAWA A, et al. A combination of circulating miRNAs for the early detection of ovarian cancer[J]. Oncotarget, 2017, 8(52): 89811-89823. doi: 10.18632/oncotarget.20688
[32]	汪义泳, 管玉宇, 杜景云, 等. 生物分子标记物在卵巢癌早期诊断中的研究进展[J]. 河北医药, 2019, 41(18): 2855-2860, 2865. doi: 10.3969/j.issn.1002-7386.2019.18.035
[33]	PALIWAL N, VASHIST M, CHAUHAN M. Evaluation of miR-22 and miR-21 as diagnostic biomarkers in patients with epithelial ovarian cancer[J]. 3Biotech, 2020, 10(3): 142. doi: 10.1007/s13205-020-2124-7?utm_source=trendmd
[34]	MENG X D, MVLLER V, MILDE-LANGOSCH K, et al. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer[J]. Oncotarget, 2016, 7(13): 16923-16935. doi: 10.18632/oncotarget.7850
[35]	ELIAS K M, FENDLER W, STAWISKI K, et al. Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer[J]. ELife, 2017, 6: e28932. doi: 10.7554/eLife.28932
[36]	杨维娜, 徐燕颖. 长链非编码RNA在卵巢癌中的研究进展[J]. 山东医药, 2020, 60(29): 91-93. doi: 10.3969/j.issn.1002-266X.2020.29.027
[37]	郑媛媛, 李伟, 陈余清. 环状RNA与肿瘤相关性研究进展[J]. 中华全科医学, 2019, 17(7): 1181-1185. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201907035.htm
[38]	CUI X L, WANG J X, GUO Z J, et al. Emerging function and potential diagnostic value of circular RNAs in cancer[J]. Mol Cancer, 2018, 17(1): 123. doi: 10.1186/s12943-018-0877-y
[39]	SHENG J Q, LIU L, WANG M R, et al. Circular RNAs in digestive system cancer: Potential biomarkers and therapeutic targets[J]. Am J Cancer Res, 2018, 8(7): 1142-1156. http://www.ajcr.us/files/ajcr0080004.pdf
[40]	CHEN Q, ZHANG J, HE Y, et al. Hsa_circ_0061140 knockdown reverses FOXM1-mediated cell growth and metastasis in ovarian cancer through miR-370 sponge activity[J]. Mol Ther Nucleic Acids, 2018, 13: 55-63. doi: 10.1016/j.omtn.2018.08.010
[41]	CHEN H, MAO M, JIANG J, et al. Circular RNA CDR1as acts as a sponge of miR-135b-5p to suppress ovarian cancer progression[J]. Onco Targets Ther, 2019, 12: 3869-3879. doi: 10.2147/OTT.S207938
[42]	LIU H, HU Y, ZHUANG B, et al. Differential expression of circRNAs in embryonic heart tissue associated with ventricular septal defect[J]. Int J Med Sci, 2018, 15(7): 703-712. doi: 10.7150/ijms.21660
[43]	KAREDATH T, AHMED I, AL AMERI W, et al. Silencing of ANKRD12 circRNA induces molecular and functional changes associated with invasive phenotypes[J]. BMC Cancer, 2019, 19(1): 565. doi: 10.1186/s12885-019-5723-0
[44]	BAO L, ZHONG J, PANG L. Upregulation of circular RNA VPS13C-has-circ-001567 promotes ovarian cancer cell proliferation and invasion[J]. Cancer Biother Radiopharm, 2019, 34(2): 110-118. doi: 10.1089/cbr.2018.2641
[45]	QIU L, XU H, JI M, et al. Circular RNAs in hepatocellular carcinoma: Biomarkers, functions and mechanisms[J]. Life Sci, 2019, 231: 116660. doi: 10.1016/j.lfs.2019.116660
[46]	FAN C M, WANG J P, TANG Y Y, et al. CircMAN 1A2 could serve as a novel serum biomarker for malignant tumors[J]. Cancer Sci, 2019, 110(7): 2180-2188. doi: 10.1111/cas.14034
[47]	XIE J, WANG S F, LI G L, et al. CircEPSTI1 regulates ovarian cancer progression via decoying miR-942[J]. J Cell Mol Med, 2019, 23(5): 3597-3602. doi: 10.1111/jcmm.14260