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CK7在浆液性卵巢癌中的研究进展
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Abstract:
卵巢癌(Ovarian Cancer, OC)是常见的妇科恶性肿瘤之一。上皮性卵巢癌(Epithelial Ovarian Cancer, EOC)在所有卵巢癌中大约占90%，其致死率在妇科肿瘤中居首位。浆液性卵巢癌(Serous Ovarian Cancer, SOC)约占上皮性卵巢癌75%，严重危害着女性身心健康。随着肿瘤基因研究不断深入，大多数学者认为浆液性卵巢癌的发生是多因素综合作用的结果，与基因改变密切相关，因此基因已成为其诊疗的新焦点。CK是由20个相关多肽链组成的多基因家族，是上皮组织中间纤维蛋白的重要组成成分。CK7是一种偏碱性的II型低分子蛋白，相对分子质量约为54 kda，其编码基因定位于人类的第12号染色体上。CK7在恶性疾病鉴别诊断、肿瘤细胞的转移、浸润及亚型确定等方面有着重要价值。研究CK7可以帮助了解卵巢癌的起源部位和致癌特性，使CK7蛋白可能成为治疗浆液性卵巢癌的期望药物靶标，从而有效抑制肿瘤细胞增殖、转移，改善患者的预后，延长其生存期。本综述主要从卵巢癌与各种免疫组化因子的关系以及CK7的生物学特征、CK7与浆液性卵巢癌的关系等方面进行介绍，为浆液性卵巢癌的临床诊断、预后评估以及指导个体化治疗提供理论依据。
Ovarian cancer (OC) is one of the most common gynecological malignancies. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian cancers and is the leading cause of death among gynecological tumors. Serous ovarian cancer (SOC) accounts for about 75% of epithelial ovarian cancers, and seriously harms women’s physical and mental health. With the deepening of tumor gene research, most scholars believe that the occurrence of serous ovarian cancer is the result of multi-factor synthesis and closely related to gene change, so gene has become a new focus of its diagnosis and treatment. CK is a multigene family composed of 20 related polypeptide chains and is an important component of intermediate fibrin in epithelial tissue. CK7 is an alkaline type II low molecular protein with a relative molecular mass of about 54 kda, and its coding gene is located on human chromosome 12. CK7 plays an important role in the differential diagnosis of malignant diseases, metastasis, invasion and subtype determination of tumor cells. The study of CK7 can help to understand the origin site and carcinogenic properties of ovarian cancer, so that CK7 protein may become a desired drug target for the treatment of serous ovarian cancer, so as to effectively inhibit the proliferation and metastasis of tumor cells, improve the prognosis of patients and prolong their survival. This review mainly introduces the relationship between ovarian cancer and various immunohistochemical factors, the biological characteristics of CK7, and the relationship between CK7 and serous ovarian cancer, providing theoretical basis for clinical diagnosis, prognosis assessment and individualized treatment of serous ovarian cancer.
| [1] | Kuroki, L. and Guntupalli, S.R. (2020) Treatment of Epithelial Ovarian Cancer. BMJ, 371, M3773. https://doi.org/10.1136/bmj.m3773 |
| [2] | Reid, B.M., Permuth, J.B. and Sellers, T.A. (2017) Epidemiology of Ovarian Cancer: A Review. Cancer Biology & Medicine, 14, 9-32. |
| [3] | H？gdall, E.V., Christensen, L., H？gdall, C.K., et al. (2007) Prognostic Value of Estrogen Receptor and Progesterone Receptor Tumor Expression in Danish Ovarian Cancer Patients: From the “MALOVA” Ovarian Cancer Study. Oncology Reports, 18, 1051-1059. |
| [4] | Wang, M., Zhang, J. and Wu, Y. (2023) Tumor Metabolism Rewiring in Epithelial Ovarian Cancer. Journal of Ovarian Research, 16, Article No. 108. https://doi.org/10.1186/s13048-023-01196-0 |
| [5] | Di Palma, T., Filippone, M.G., Pierantoni, G.M., et al. (2013) Pax8 Has a Critical Role in Epithelial Cell Survival and Proliferation. Cell Death & Disease, 4, e729. https://doi.org/10.1038/cddis.2013.262 |
| [6] | Siegel, R.L., Miller, K.D., Wagle, N.S., Wagle, N.S., et al. (2023) Cancer Statistics, 2023. CA: A Cancer Journal for Clinicians, 73, 17-48. https://doi.org/10.3322/caac.21763 |
| [7] | Eckert, M.A., Pan, S., Hernandez, K.M., et al. (2016) Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube. Cancer Discovery, 6, 1342-1351. https://doi.org/10.1158/2159-8290.CD-16-0607 |
| [8] | Ducie, J., Dao, F., Considine, M., et al. (2017) Molecular Analysis of High-Grade Serous Ovarian Carcinoma with and without Associated Serous Tubal Intra-Epithelial Carcinoma. Nature Communications, 8, Article No. 990. https://doi.org/10.1038/s41467-017-01217-9 |
| [9] | Karnezis, A.N., Cho, K.R., Gilks, C.B., et al. (2017) The Disparate Origins of Ovarian Cancers: Pathogenesis and Prevention Strategies. Nature Reviews Cancer, 17, 65-74. https://doi.org/10.1038/nrc.2016.113 |
| [10] | Dai, L., Song, Q., Li, L., et al. (2001) Expression of Cytokeratin 7 and 20 in Ovarian Metastatic Carcinomas. Chinese Journal of Pathology, 30, 114-117. |
| [11] | Schlüter, C., Duchrow, M., Wohlenberg, C., et al. (1993) The Cell Proliferation-Associated Antigen of Antibody Ki-67: A Very Large, Ubiquitous Nuclear Protein with Numerous Repeated Elements, Representing a New Kind of Cell Cycle-Maintaining Proteins. Journal of Cell Biology, 123, 513-522. https://doi.org/10.1083/jcb.123.3.513 |
| [12] | Libé, R., Pais, A., Violon, F., et al. (2023) Positive Correlation between 18F-FDG Uptake and Tumor-Proliferating Antigen Ki-67 Expression in Adrenocortical Carcinomas. Clinical Nuclear Medicine, 48, 381-386. https://doi.org/10.1097/RLU.0000000000004593 |
| [13] | Zhang, M., Meng, L., Zhang, Z., et al. (2022) The Relationships of OSBPL3 Expression with KI-67 Expression and KRAS Mutations in CRC: Implications for Diagnosis and Prognosis. BMC Med Genomics, 15, Article No. 259. https://doi.org/10.1186/s12920-022-01402-w |
| [14] | Qiu, D., Cai, W., Zhang, Z., Li, H. and Zhou, D. (2019) High Ki-67 Expression Is Significantly Associated with Poor Prognosis of Ovarian Cancer Patients: Evidence from a Meta-Analysis. Archives of Gynecology and Obstetrics, 299, 1415-1427. https://doi.org/10.1007/s00404-019-05082-3 |
| [15] | Levine, A.J. (2020) P53: 800 Million Years of Evolution and 40 Years of Discovery. Nature Reviews Cancer, 20, 471-480. https://doi.org/10.1038/s41568-020-0262-1 |
| [16] | Kastenhuber, E.R. and Lowe, S.W. (2017) Putting P53 in Context. Cell, 170, 1062-1078. https://doi.org/10.1016/j.cell.2017.08.028 |
| [17] | Schlomm, T. (2020) Ergebnisse des “ICGC/TCGA Pan-Cancer Analysis of the Whole Genomes” (PCWAG)-Konsortiums [Results of the CGC/TCGA Pan-Cancer Analysis of the Whole Genomes (PCAWG) Consortium]. Der Urologe, 59, 1552-1553. https://doi.org/10.1007/s00120-020-01373-9 |
| [18] | Bykov, V.J.N., Eriksson, S.E., Bianchi, J., et al. (2018) Targeting Mutant P53 for Efficient Cancer Therapy. Nature Reviews Cancer, 18, 89-102. https://doi.org/10.1038/nrc.2017.109 |
| [19] | Sullivan, K.D., Galbraith, M.D., Andrysik, Z., et al. (2018) Mechanisms of Transcriptional Regulation by P53. Cell Death & Differentiation, 25, 133-143. https://doi.org/10.1038/cdd.2017.174 |
| [20] | Wang, C.K., Chen, T.J., Tan, G.Y.T., et al. (2023) MEX3A Mediates P53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis. Cancer Research, 83, 251-263. https://doi.org/10.1158/0008-5472.CAN-22-1159 |
| [21] | Shi, H.R. and Zhang, R.T. (2009) Expression and Significance of P53, P21WAF1 and CDK1 Proteins in Epithelial Ovarian Cancer. Chinese Journal of Cancer, 28, 882-885. https://doi.org/10.5732/cjc.008.10417 |
| [22] | Okal, A., Cornillie, S., Matissek, S.J., et al. (2014) Re-Engineered P53 Chimera with Enhanced Homo-Oligomerization That Maintains Tumor Suppressor Activity. Molecular Pharmaceutics, 11, 2442-2452. https://doi.org/10.1021/mp500202p |
| [23] | Havrilesky, L.J., Alvarez, A.A., Whitaker, R.S., et al. (2001) Loss of Expression of the P16 Tumor Suppressor Gene Is More Frequent in Advanced Ovarian Cancers Lacking P53 Mutations. Gynecologic Oncology, 83, 491-500. https://doi.org/10.1006/gyno.2001.6464 |
| [24] | Němejcová, K., ？afanda, A., Bárt？, M.K., et al. (2023) A Comprehensive Immunohistochemical Analysis of 26 Markers in 250 Cases of Serous Ovarian Tumors. Diagnostic Pathology, 18, Article No. 32. https://doi.org/10.1186/s13000-023-01317-9 |
| [25] | Makarla, P.B., Saboorian, M.H., Ashfaq, R., et al. (2005) Promoter Hypermethylation Profile of Ovarian Epithelial Neoplasms. Clinical Cancer Research, 11, 5365-5369. https://doi.org/10.1158/1078-0432.CCR-04-2455 |
| [26] | Katsaros, D., Cho, W., Singal, R., et al. (2004) Methylation of Tumor Suppressor Gene P16 and Prognosis of Epithelial Ovarian Cancer. Gynecologic Oncology, 94, 685-692. https://doi.org/10.1016/j.ygyno.2004.06.018 |
| [27] | Gessler, M., Poustka, A., et al. (1990) Homozygous Deletion in Wilms Tumours of a Zinc-Finger Gene Identified by Chromosome Jumping. Nature, 343, 774-778. https://doi.org/10.1038/343774a0 |
| [28] | McCluggage, W.G. (2011) Morphological Subtypes of Ovarian Carcinoma: A Review with Emphasis on New Developments and Pathogenesis. Pathology, 43, 420-432. https://doi.org/10.1097/PAT.0b013e328348a6e7 |
| [29] | McCluggage, W.G. (2004) WT1 Is of Value in Ascertaining the Site of Origin of Serous Carcinomas within the Female Genital Tract. International Journal of Gynecological Pathology, 23, 97-99. https://doi.org/10.1097/00004347-200404000-00002 |
| [30] | Hohenstein, P. and Hastie, N.D. (2006) The Many Facets of the Wilms’ Tumour Gene, WT1. Human Molecular Genetics, 15, R196-R201. https://doi.org/10.1093/hmg/ddl196 |
| [31] | Rekhi, B., Deodhar, K.K., Menon, S., et al. (2018) Napsin A and WT 1 Are Useful Immunohistochemical Markers for Differentiating Clear Cell Carcinoma Ovary from High-Grade Serous Carcinoma. APMIS, 126, 45-55. https://doi.org/10.1111/apm.12784 |
| [32] | Zarychta, E., Lepinay, K., Szubert, S., et al. (2020) Wilms’ Tumor 1 Antigen Immunoreactivity in Epithelial Ovarian Cancer—Diagnostic and Prognostic Value. Folia Histochemica et Cytobiologica, 58, 198-207. https://doi.org/10.5603/FHC.a2020.0022 |
| [33] | Stigbrand, T. (2001) The Versatility of Cytokeratins as Tumor Markers. Tumor Biology, 22, 1-3. https://doi.org/10.1159/000030148 |
| [34] | Li, M., Shang, Y.-X., Wei, B. and Yang, Y.-G. (2011) The Effect of Substance P on Asthmatic Rat Airway Smooth Muscle Cell Proliferation, Migration, and Cytoplasmic Calcium Concentration in Vitro. Journal of Inflammation (London), 8, 18. |
| [35] | Dum, D., Menz, A., et al. (2022) Cytokeratin 7 and Cytokeratin 20 Expression in Cancer: A Tissue Microarray Study on 15,424 Cancers. Experimental and Molecular Pathology, 126, Article ID: 104762. https://doi.org/10.1016/j.yexmp.2022.104762 |
| [36] | Ascoli, V., Taccogna, S., et al. (1995) Utility of Cytokeratin 20 in Identifying the Origin of Metastatic Carcinomas in Effusions. Diagnostic Cytopathology, 12, 303-308. https://doi.org/10.1002/dc.2840120404 |
| [37] | Shin, J.H., Bae, J.H., Lee, A., et al. (2010) CK7, CK20, CDX2 and MUC2 Immunohistochemical Staining Used to Distinguish Metastatic Colorectal Carcinoma Involving Ovary from Primary Ovarian Mucinous Adenocarcinoma. Japanese Journal of Clinical Oncology, 40, 208-213. https://doi.org/10.1093/jjco/hyp150 |
| [38] | Pasternak, S., Carter, M.D., Ly, T.Y., et al. (2018) Immunohistochemical Profiles of Different Subsets of Merkel Cell Carcinoma. Human Pathology, 82, 232-238. https://doi.org/10.1016/j.humpath.2018.07.022 |
| [39] | Fei, F., Li, C., Cao, Y., et al. (2019) CK7 Expression Associates with the Location, Differentiation, Lymph Node Metastasis, and the Dukes’ Stage of Primary Colorectal Cancers. Journal of Cancer, 10, 2510-2519. https://doi.org/10.7150/jca.29397 |
| [40] | Kim, M.A., Lee, H.S., Yang, H.K., et al. (2004) Cytokeratin Expression Profile in Gastric Carcinomas. Human Pathology, 35, 576-581. https://doi.org/10.1016/j.humpath.2003.12.007 |
| [41] | Bai, S., Lindberg, J., Whalen, G., et al. (2021) Utility of HNF-1B and a Panel of Lineage-Specific Biomarkers to Optimize the Diagnosis of Pancreatic Ductal Adenocarcinoma. American Journal of Cancer Research, 11, 858-865. |
| [42] | Sree, U.D., Prayaga, A.K., Reddy, V.V., et al. (2022) Differential Expression of CK7, CK20, CDX2 in Intestinal and Pancreatobiliary Types of Preriampullary Carcinoma. Indian Journal of Pathology and Microbiology, 65, 42-48. |
| [43] | Ji, R., Li, Y., He, C., et al. (2020) Detection and Analysis of Multiple Biomarkers in Ovarian Cancer: Clinical Significance in Diagnosis, Treatment, and Prognosis Evaluation. Gland Surgery, 9, 2175-2186. https://doi.org/10.21037/gs-20-811 |
| [44] | 何娟, 黄林, 孙奇, 等. 检测原发性卵巢癌和转移性卵巢癌CDX2、CK7、CA_(125)表达的临床意义[J]. 实用妇产科杂志, 2017, 33(2): 141-144. |
| [45] | 孙凯旋, 陈曦, 陈说, 等. CK7和CA125在人卵巢癌的表达及意义[J]. 解剖科学进展, 2014, 20(3): 237-239 245. https://doi.org/10.16695/j.cnki.1006-2947.2014.03.017 |
| [46] | 潘秀芳, 郑志昂, 麦燕. 血清附睾蛋白4、糖类抗原125及19-9水平在老年卵巢癌诊断及病理类型鉴别中的临床价值[J]. 中国老年学杂志, 2015, 35(12): 3343-3344. |
