Progress in understanding of role of MUC16/CA125 in diagnosis and treatment of benign and malignant tumors

doi:10.3877/cma.j.issn.1674-0785.2023.05.016

Abstract

Abstract:

MUC16/CA125 is a kind of glycoprotein tumor marker that can originate from mesothelial cells, Miller duct epithelium in benign tissue, and their derivatives in malignant diseases. MUC16/CA125 has different roles in benign and malignant tumors. On the one hand, it participates in the occurrence and development of malignant tumors through signaling pathways such as MUC16-siglec-9, MUC16-galectin-1/3, MUC16-mesothelin, MUC16-selectin, and MUC16-JAK2. On the other hand, it mainly has the functions of local buffering, lubrication, anti-inflammation, and maintaining homeostasis in non-malignant tumors. In this paper, we discuss the identification of diseases related to elevated serum CA125 and its role in the diagnosis and treatment of benign and malignant tumors. Further research is needed to explore MUC16/CA125 as a new specific tumor marker and target for new drugs.

Key words: MUC16/CA125, Benign and malignant tumors, Role, Research progress

Yihan Wu, Zhang Lei, Hongda Lu. Progress in understanding of role of MUC16/CA125 in diagnosis and treatment of benign and malignant tumors[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(05): 591-595.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhlcyszz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0785.2023.05.016

https://zhlcyszz.cma-cmc.com.cn/EN/Y2023/V17/I05/591

References 60

1	Tang Y, Cui Y, Zhang S, et al. The sensitivity and specificity of serum glycan-based biomarkers for cancer detection [J]. Prog Mol Biol Transl Sci, 2019, 162: 121-140.
2	Bast RC, Feeney M, Lazarus H, et al. Reactivity of a monoclonal antibody with human ovarian carcinoma [J]. J Clin Invest, 1981, 68(5): 1331-1337.
3	O'brien T, Beard J, Underwood L, et al. The CA125 gene: an extracellular superstructure dominated by repeat sequences [J]. Tumor Biol, 2001, 22(6): 348-366.
4	Tolman CJ, Vaid T, Schreuder HWR. Extremely elevated CA125 in benign ovarian disease due to stretch of the peritoneum [J]. BMJ, 2012, 2012: bcr2012006664.
5	Kabawat SE, Bast RC, Bhan AK, et al. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125 [J]. Int J Gynecol Pathol, 1983, 2(3): 275-285.
6	Das S, Batra S. Understanding the unique attributes of MUC16 (CA125): potential implications in targeted therapy [J]. Cancer Res, 2015, 75(22): 4669-4674.
7	范艳佳, 陈美红, 颜林林. 化学发光免疫法在肿瘤生物标志物检测中的应用价值 [J]. 实用预防医学, 2021, 28(11): 1397-1400.
8	Li J, Wang X, Qu W, et al. Comparison of serum human epididymis protein 4 and CA125 on endometrial cancer detection: a meta-analysis [J]. Clin Chim Acta, 2019, 488: 215-220.
9	Rao TD, Tian H, Ma X, et al. Expression of the carboxy-terminal portion of MUC16/CA125 induces transformation and tumor invasion [J]. PLoS One, 2015, 10(5): e0126633.
10	Das S, Majhi PD, Al-Mugotir MH, et al. Membrane proximal ectodomain cleavage of MUC16 occurs in the acidifyingGolgi/post-Golgi compartments [J]. Sci Rep, 2015, 5(1): 1-11.
11	Lee DH, Choi S, Park Y, et al. Mucin1 and mucin16: The rapeutic targets for cancer therapy [J]. Pharmaceuticals, 2021, 14(10): 1053.
12	Akita K, Tanaka M, Tanida S, et al. CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion [J]. Eur J Cell Biol, 2013, 92(8-9): 257-263.
13	Nomoto M, Konopaske GT, Yamashita N, et al. Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia [J]. Proc Natl Acad Sci U S A, 2021, 118(31): e2100032118.
14	Schummer M, Ng WV, Bumgarner RE, et al. Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas [J]. Gene, 1999, 238(2): 375-385.
15	黄可, 徐娟, 贾雪梅. 卵巢癌相关糖蛋白分子标志物及其促癌机制的研究进展 [J]. 肿瘤学杂志, 2020, 26(9): 833-837.
16	王兰兰, 焦凤琴. 人附睾分泌蛋白4联合血清CA125检测诊断卵巢癌的价值 [J]. 中国妇幼保健, 2018, 33(6): 1237-1238.
17	Dochez V, Caillon H, Vaucel E, et al. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE₄, RMI and ROMA, a review [J]. J Ovarian Res, 2019, 12(1): 28.
18	Jacobs I, Oram D, Fairbanks J, et al. A risk of malignancy index incorporating CA125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer [J]. BJOG, 1990, 97(10): 922-929.
19	Moore RG, Mcmeekin DS, Brown AK, et al. A novel multiple marker bioassay utilizing HE₄ and CA125 for the prediction of ovarian cancer in patients with a pelvic mass [J]. Gynecol Oncol, 2009, 112(1): 40-46.
20	Karlsen MA, Høgdall EVS, Christensen IJ, et al. A novel diagnostic index combining HE₄, CA125 and age may improve triage of women with suspected ovarian cancer - An international multicenter study in women with an ovarian mass [J]. Gynecol Oncol, 2015, 138(3): 640-646.
21	Moore RG, Brown A K, Miller MC, et al. Utility of a novel serum tumor biomarker HE₄ in patients with endometrioid adenocarcinoma of the uterus [J]. Gynecol Oncol, 2008, 110 (2): 196-201.
22	孙艳艳, 井水, 杨大平, 等. 子宫内膜癌患者血清CA125、CA199、SCC-Ag表达水平及其临床意义 [J]. 医学综述, 2022, (3): 615-618, 624.
23	尹利娟, 陈龙梅. CA125在呼吸科疾病中的诊断价值 [J]. 医学信息, 2020, 33(19): 165-167, 170.
24	张波, 李明东, 单立群. 非小细胞肺癌患者血清可溶性B₇-H₄的表达及其与临床病理特征的关系 [J]. 中国基层医药, 2017, 24(13): 1965-1969.
25	Hatzakis KD, Froudarakis ME, Bouros D, et al. Prognostic value of serum tumor markers in patients with lung cancer [J]. Respiration, 2002, 69(1): 25-29.
26	李标, 张有为. CRP、CEA及CA125表达水平与非小细胞肺癌患者行VATS术后疗效及预后的相关性 [J]. 临床肺科杂志, 2020, 25(5): 724-729.
27	Li Z, Zhao J. Clinical efficacy and safety of crizotinib and alectinib in ALK-positive non-small cell lung cancer treatment and predictive value of CEA and CA125 for treatment efficacy [J]. Am J Transl Res, 2021, 13(11): 13108-13116.
28	Wang J, Chu Y, Li J, et al. Development of a prediction model with serum tumor markers to assess tumor metastasis in lung cancer [J]. Cancer Med, 2020, 9(15): 5436-5445.
29	Ma S, Shen L, Qian N, et al. The prognostic values of CA125, CA199, NSE, AND SCC for stage I NSCLC are limited [J]. Cancer Biomark, 2011, 10(3-4): 155-162.
30	Chu L, Peng Y, Weng X, et al. Blood-based biomarkers for early detection of esophageal squamous cell carcinoma [J]. World J Gastroenterol, 2020, 26(15): 1708-1725.
31	李田田, 薛文华, 秦迁, 等. 糖类抗原125、癌胚抗原和神经特异性烯醇酶联合检测在食管鳞癌诊断中的应用价值 [J]. 肿瘤基础与临床, 2021, 34(4): 311-313.
32	亢晓春, 张清琴, 陆志红, 等. CA125、CA50、CEA在贲门癌患者体内变化意义研究 [J]. 齐齐哈尔医学院学报, 2021, 42(10): 838-840.
33	翁艳, 褚云香, 王东盛, 等. CEA、CA125、CA19-9对胃癌的诊断价值及与TNM分期、淋巴结转移的关系 [J]. 癌症进展, 2019, 17(5): 582-584.
34	王章奇, 杨俊, 彭享, 等. 血清HIF-1α、CA125、CEA、CA19-9联合检测对结直肠癌患者术后早期复发转移的预测价值 [J]. 中国医药科学, 2019, 9(6): 7-10.
35	Kwanpeemai P, Andrew D. Diagnostic and prognostic role of peritoneal CA125 in peritoneal dialysis patients presenting with acute peritonitis [J]. BMC Nephrol, 2014, 15: 149.
36	袁昌丽, 段秀清, 喻昆林. 以CA125升高的结核性腹膜炎一例 [J]. 云南医药, 2021, 42(05): 507-508, 496.
37	黎增辉. 血清AFP-L3%、CA125、CA199和IL-6变化与乙肝后肝硬化和癌变的相关性研究 [J]. 临床输血与检验, 2019, 21(5): 535-539.
38	聂荣慧, 刘元元. 肿瘤标志物AFP、CA125、CA199和CEA检测在肝炎、肝硬化患者诊断和治疗中的应用 [J]. 吉林大学学报(医学版), 2012, 38(1): 119-122.
39	Kayadibi H, Sertoglu E, Uyanik M. Evaluation of relationship between CA125 levels and ascites in patients with liver cirrhosis [J]. J Coll Physicians Surg Pak, 2014, 24(11): 873.
40	朱壹澎, 卢高峰, 孙趁意, 等. 肝硬化患者血清CA125水平升高的相关因素分析 [J]. 中国全科医学, 2019, 22(21): 2577-2581.
41	王雯, 徐婷, 孙甜甜, 等. 类风湿关节炎合并活动性肺结核病的临床特征及相关因素分析 [J]. 中国感染与化疗杂志, 2021, 21(2): 158-164.
42	高见, 纪青. 不典型与典型肺结核痰抗酸杆菌、糖类抗原125、D-二聚体、腺苷脱氨酶检测结果对比 [J]. 中国现代医药杂志, 2021, 23(12): 26-29.
43	杨建和, 张蔚华. CA125在恶性及结核性胸水中鉴别诊断价值的探讨 [J]. 医师进修杂志, 2000, (7): 27-28.
44	何彦侠, 薛兵, 赵淑敏. 癌抗原125在常见非恶性呼吸疾病中的应用研究进展 [J]. 2015, 50(10): 48-50.
45	王颖颖. 冠心病患者血清CA125、CysC、OPG中的水平变化及意义 [J]. 中国卫生工程学, 2021, 20(5): 839-840.
46	胡欣, 李月芳, 赵红, 等. 高龄慢性心力衰竭患者血清CA125、尿酸水平与心功能的相关性 [J]. 心血管康复医学杂志, 2018, 27(1): 12-15.
47	Hamdy NM. Relationship between pro-anti-inflammatory cytokines, T-cell activation and CA125 in obese patients with heart failure [J]. Med Sci Monit, 2011, 17(3): CR173.
48	Huang F, Chen J, Liu Y, et al. New mechanism of elevated CA125 in heart failure: the mechanical stress and inflammatory stimuli initiate CA125 synthesis [J]. Med Hypotheses, 2012, 79(3): 381-383.
49	Núñez J, Minana G, Núñez E, et al. Clinical utility of antigen carbohydrate 125 in heart failure [J]. Heart Fail Rev, 2014, 19(5): 575-584.
50	戈程, 李佳月, 刘博罕, 等. 心肌淀粉样变性临床特点及远期预后的影响因素 [J]. 中华老年多器官疾病杂志, 2020, 19(6): 405-409.
51	古晓燕, 龚德华. 慢性肾脏病患者血清肿瘤标志物检测的意义 [J]. 中国血液净化, 2020, 19(10): 699-702.
52	齐娟飞, 朱海燕. 月经周期对CA125的影响 [J]. 母婴世界, 2015, 1(2): 125.
53	Kafali H, Artunc H, Erdem M. Evaluation of factors that may be responsible for cyclic change of CA125 levels during menstrual cycle [J]. Arch Gynecol Obstet, 2007, 3(275): 175-177.
54	Spitzer M, Kaushal N, Benjamin F. Maternal CA125 levels in pregnancy and the puerperium [J]. J Reprod Med, 1998, 43(4): 387-392.
55	邹晓静, 朱诗呈, 李春梅. 温州地区孕妇CA125参考区间的建立及应用 [J]. 放射免疫学杂志, 2012, 25(4): 474-475.
56	王宜生. CA125升高患者的良恶性鉴别方法研究 [博士学位论文]. 上海: 复旦大学, 2012.
57	White B, Patterson M, Karnwal S, et al. Crystal structure of a human MUC16 SEA domain reveals insight into the nature of the CA125 tumor marker [J]. Proteins, 2022, 90(5): 1210-1218.
58	Brewer M, Angioli R, Scambia G, et al. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study [J]. Gynecol Oncol, 2020, 156(3): 523-529.
59	Reinartz S, Köhler S, Schlebusch H, et al. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II) [J]. Clin Cancer Res, 2004, 10(5): 1580-1587.
60	Liu JF, Moore KN, Birrer MJ, et al. Phase I study of safety and pharmacokinetics of the anti-MUC16 antibody-drug conjugate DMUC5754A in patients with platinum-resistant ovarian cancer or unresectable pancreatic cancer [J]. Ann Oncol, 2016, 27(11): 2124-2130.

[1]	Yongbo Zhang, Liang Zhang, Liuyang Chen, Rui Dai, Hua Sun, Sheng Yang, Bo Meng, Qing Peng. Mitochondrial and intervertebral disc degeneration [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(03): 265-269.
[2]	Yijun Fan, Feng Yang, Wei Wang, Heying Yin, Jun Liu. Research progress in the diagnostic and therapeutic value of Delphian lymph node metastasis in papillary thyroid carcinoma [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(04): 306-310.
[3]	Binru Zhang, Hua Chen, Bei Sun. Status and prospect of pancreaticojejunostomy in pancreaticoduodenectomy [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2022, 16(04): 465-468.
[4]	Ni Yan, Junkang Dong, Mingzhou Zhang, Binfeng He, Yu Liu, Zhenghua Wei, Zhan Gao, Guansong Wang. Effect of anxiety and depression on quality of life in patients with chronic obstructive pulmonary disease and mediating effect of medication compliance [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(06): 771-775.
[5]	Fuhao Qin, Zheng Zheng, Bin Jiang. Research progress of mesenchymal stem cells in the treatment of perianal fifistulizing Crohn's disease [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(03): 172-177.
[6]	Junjie Huang, Lie Wang, Hu Zhao, Yin Xia, Zaizhong Zhang. Progress in the mechanism of lncRNA as ceRNA involved in the pathogenesis and progression of infantile hemangioma [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(06): 360-366.
[7]	Bing Lan, Huaiming Wang, Hui Wang, Bo Ma. Research progress on locally advanced colon cancer with bladder invasion [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2023, 12(06): 505-511.
[8]	Xiaoyu Liang, Jie Mi. Research progress on phospholipase A2 receptor-related idiopathic membranous nephropathy [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(01): 52-56.
[9]	Hengyu Luan, Xiaoyong Sai. Treatment status and research progress of post-traumatic stress disorder [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2023, 09(02): 112-118.
[10]	Wenpeng Huang, Yongkang Qiu, Qi Yang, Lele Song, Zhao Chen, Yan Fan, Lei Kang. Research progress of PET related radiomics in tumor prognosis [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(02): 104-110.
[11]	Ying Xu, Feng Ye, Xinming Zhao. Research progress of application of dual-energy computed tomography in radiological diagnosis of liver diseases [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2022, 12(04): 241-245.
[12]	Ying Xu, Xiaohong Ma, Xinming Zhao. Research progress of nonalcoholic fatty pancreas disease [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2022, 12(01): 46-51.
[13]	Yang Gou, Qing Jiang. Clinical application of percutaneous nephrolithotomy for kidney stones and risk factors for postoperative urogenic sepsis [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(02): 183-186.
[14]	Kai She, Danmei Ma, Jun He. Clinical advances in auricular therapy [J]. Chinese Journal of Acupuncture and Moxibustion(Electronic Edition), 2022, 11(03): 111-112,122.
[15]	Ze Wang, Baojun Wang, Weize Zhang. Research progress in stroke rehabilitation [J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2022, 16(04): 221-224.

Please choose a citation manager

Content to export