CD44和MMP-9在RCC中的表达和CTC分类呈正相关
The Expression of CD44 and MMP-9 in RCC Is Positively Correlated with CTC Classification
DOI: 10.12677/ACM.2024.141053, PDF,   
作者: 朱延杰*:空军军医大学基础医学院,陕西 西安;贺少菲:陕西中医药大学医学技术学院,陕西 咸阳;柴 佳, 彭 阳#:陕西省空军军医大学西京医院病理科,陕西 西安;刘一雄, 马 静#:陕西省空军军医大学基础医学院病理学教研室,陕西 西安
关键词: 肾细胞癌CD44MMP-9CTC预后Renal Cell Carcinoma CD44 MMP-9 CTC Prognosis
摘要: 肾细胞癌(RCC)是所有泌尿生殖系统癌中最常见的恶性肿瘤类型,其发病率迅速上升。在此,我们研究了CD44和MMP-9在肾细胞癌(RCC)中的表达与患者的临床病理特征以及循环肿瘤细胞(CTC)之间的关系。共鉴定出114例肿瘤和非癌性肾组织样本。我们回顾了现有的临床记录。采用免疫组化方法检测104例RCC标本和10例非癌性肾组织标本中CD44和MMP-9的表达。采用阳性富集法进行CTC试验和分类。我们发现MMP-9和CD44的阳性表达率分别为69.2%和65%。肾细胞癌患者的发病率分别高于正常肾组织患者(P < 0.05)。MMP-9和CD44的表达与WHO/ISUP核仁分级相关(P < 0.05)。CTC阳性患者中MMP-9和CD44阳性的阳性表达率(分别为60.6%和57.7%)显著高于CTC阴性患者(8.7%和7.7%;P < 0.05)。间充质型CTC患者RCC中MMP-9和CD44的阳性表达率高于混合型和上皮型CTC患者。综上所述,MMP-9和CD44过表达与肾细胞癌的病理分级、CTC数量和分类相关,提示它们可能是潜在的预后因素,成为RCC患者新的潜在治疗靶点。
Abstract: Renal cell carcinoma (RCC) is the most common malignant tumor type of all genitourinary cancers, and morbidity increases rapidly. Herein, we investigated the relationship between the expression of CD44 and MMP-9 in renal cell carcinoma (RCC) and the clinicopathological features of patients as well as circulating tumor cells (CTC). A total of 114 tumors and non-cancerous kidney tissue samples were identified. Available clinical records were reviewed. The expression of CD44 and MMP-9 in 104 RCC samples and 10 non-cancerous kidney tissue samples were detected by immunohistochemistry. Positive enrichment method was used for CTC test and classification. We found the positive expres-sion rates of MMP-9 (69.2%) and CD44 (65.4%) were higher in RCC than those in normal kidney tissues (P < 0.05). The expression of MMP-9 and CD44 is associated with WHO/ISUP nucleolar grades (P < 0.05). The positive expression rates of MMP-9 and CD44 in patients with positive CTC test results (60.6% and 57.7%, respectively) are significantly higher than those with negative CTC test results (8.7% and 7.7%, respectively; P < 0.05). The positive expression rates of MMP-9 and CD44 in the RCC of patients with mesenchymal-type CTC are higher than those in patients with mixed and epithelial-type CTC. In conclusions, MMP-9 and CD44 overexpression is associated with RCC pathological grade, CTC quantity and classification, indicating that they could be potential prognostic factors and serve as new potential therapeutic targets for RCC patients.
文章引用:朱延杰, 贺少菲, 柴佳, 刘一雄, 彭阳, 马静. CD44和MMP-9在RCC中的表达和CTC分类呈正相关[J]. 临床医学进展, 2024, 14(1): 363-372. https://doi.org/10.12677/ACM.2024.141053

参考文献

[1] Siegel, R.L., Miller, K.D. and Jemal, A. (2019) Cancer Statistics, 2019. CA: A Cancer Journal for Clinicians, 69, 7-34. [Google Scholar] [CrossRef] [PubMed]
[2] Fan, L., Li, P., Yin, Z., et al. (2013) Ribosomal s6 Protein Kinase 4: A Prognostic Factor for Renal Cell Carcinoma. British Journal of Cancer, 109, 1137-1146. [Google Scholar] [CrossRef] [PubMed]
[3] Zhang, W.W., Rong, Y., Liu, Q., et al. (2018) Integrative Diagnosis of Cancer by Combining CTCs and Associated Peripheral Blood Cells in Liquid Biopsy. Clinical & Translational Oncology, 21, 828-835. [Google Scholar] [CrossRef] [PubMed]
[4] Erdoğan, F., Demirel, A. and Polat, O. (2004) Prognostic Sig-nificance of Morphologic Parameters in Renal Cell Carcinoma. International Journal of Clinical Practice, 58, 333-336. [Google Scholar] [CrossRef] [PubMed]
[5] Takenoue, T., Kitayama, J., Takei, Y., et al. (2000) Charac-terization of Dihydropyrimidine Dehydrogenase on Immunohistochemistry in Colon Carcinoma, and Correlation between Immunohistochemical Score and Protein Level or Messenger RNA Expression. Annals of Oncology, 11, 273-279. [Google Scholar] [CrossRef
[6] Zhong, G.X., Feng, S.D., Shen, R., Wu, Z.Y., Chen, F. and Zhu, X. (2017) The Clinical Significance of the Ezrin Gene and Circulating Tumor Cells in Osteosarcoma. OncoTargets and Therapy, 10, 527-533. [Google Scholar] [CrossRef
[7] Wu, S., Liu, S., Liu, Z., et al. (2015) Classification of Circulating Tu-mor Cells by Epithelial-Mesenchymal Transition Markers. PLOS ONE, 10, e0123976. [Google Scholar] [CrossRef] [PubMed]
[8] Zhang, S., Wu, T., Peng, X., et al. (2017) Mesenchymal Phe-notype of Circulating Tumor Cells Is Associated with Distant Metastasis in Breast Cancer Patients. Cancer Management and Research, 9, 691-700. [Google Scholar] [CrossRef
[9] Patricia, G.S., Gema, M.B., Francisco, P. and Amparo, C. (2017) Present and Future in Clinical Oncology. Molecular Oncology, 11, 718-738. [Google Scholar] [CrossRef] [PubMed]
[10] Chambers, A.F. and Matrisian, L.M. (1997) Changing Views of the Role of Matrix Metalloproteinases in Metastasis. Journal of the National Cancer Institute, 89, 1260-1270. [Google Scholar] [CrossRef] [PubMed]
[11] Samira, K., Mohammadhossein, H., Alireza, H., Yaser, P., Su, Y.W. and Cory, J.X. (2019) Opioids and Matrix Metalloproteinases: The Influence of Morphine on MMP-9 Production and Cancer Progression. Naunyn-Schmiedeberg’s Archives of Pharmacology, 392, 123-133.
[12] Aruna, and Li, L.M. (2018) Overexpression of Golgi Membrane Protein 1 Promotes Non-Small-Cell Carcinoma Aggressiveness by Regulating the Matrix Metallopeptidase 13. American Journal of Cancer Research, 8, 551-565.
[13] Okamoto, I., Kawano, Y., Mura-kami, D., et al. (2001) Proteolytic Release of CD44 Intracellular Domain and Its Role in the CD44 Signaling Pathway. The Journal of Cell Biology, 155, 755-762. [Google Scholar] [CrossRef] [PubMed]
[14] Liang, Y., Yang, N., Pan, G., Jin, B., Wang, S. and Ji, W. (2018) Elevated IL-33 Promotes Expression of MMP2 and MMP9 via Activating STAT3 in Alveolar Macrophages during LPS-Induced Acute Lung Injury. Cellular & Molecular Biology Letters, 23, Article No. 52. [Google Scholar] [CrossRef] [PubMed]
[15] Mimeault, M. and Batra, S.K. (2014) Molecular Biomarkers of Cancer Stem/Progenitor Cells Associated with Progression, Metastases, and Treatment Resistance of Ag-gressive Cancers. Cancer Epidemiology, Biomarkers & Prevention, 23, 234-254. [Google Scholar] [CrossRef
[16] Moon, D.H., Lindsay, D.P., Hong, S. and Wang, A.Z. (2018) Clinical Indications for, and the Future of, Circulating Tumor Cells. Advanced Drug Delivery Reviews, 125, 143-150. [Google Scholar] [CrossRef] [PubMed]
[17] Hench, I.B., Hench, J. and Tolnay, M. (2018) Liquid Biopsy in Clinical Management of Breast, Lung, and Colorectal Cancer. Frontiers in Medicine, 5, Article 9. [Google Scholar] [CrossRef] [PubMed]
[18] Vasudha, M., Rishindra, M.R., Shamileh, F., et al. (2017) Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers. Cancer Research, 77, 5194-5206. [Google Scholar] [CrossRef
[19] Mikami, S., Oya, M., Mizuno, R., Kosaka, T., Katsube, K. and Okada, Y. (2014) Invasion and Metastasis of Renal Cell Carcinoma. Medical Molecular Morphology, 47, 63-67. [Google Scholar] [CrossRef] [PubMed]
[20] Praharaj, P.P., Bhutia, S.K., Nagrath, S., Bitting, R.L. and Deep, G. (2018) Current Challenges and Promises in Medical Research and Precision Medicine. Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, 1869, 117-127. [Google Scholar] [CrossRef] [PubMed]
[21] Škovierová, H., Okajčeková, T., Strnádel, J., Vidomanová, E. and Halašová, E. (2018) Molecular Regulation of Epithelial-to-Mesenchymal Transition in Tumorigenesis (Review). Interna-tional Journal of Molecular Medicine, 41, 1187-1200.