山东大学耳鼻喉眼学报 ›› 2024, Vol. 38 ›› Issue (3): 12-17.doi: 10.6040/j.issn.1673-3770.0.2023.097
• 论著 • 上一篇
王靖淞1,余灿1,张西1,邓启成1,谢卓良1,赵锐1,温蓓2,刘海1
WANG Jingsong1, YU Can1, ZHANG Xi1, DENG Qicheng1, XIE Zhuoliang1, ZHAO Rui1, WEN Bei2, LIU Hai1
摘要: 目的 探讨角蛋白4(keratin 4,KRT4)在喉癌患者中的表达水平与临床病理特征及预后之间的关系。 方法 收集喉癌组织标本70例、对应癌旁正常黏膜组织标本70例和声带息肉组织标本40例,采用免疫组化SP法和统计学分析KRT4表达与喉癌的临床病理特征及预后之间的关系。 结果 免疫组化SP法显示,KRT4在喉癌组织的表达水平明显低于癌旁正常黏膜组织、声带息肉组织,差异具有统计学意义(χ2=51.511,P<0.001)。KRT4的表达水平与患者的临床分期(χ2=5.741,P=0.017)、分化程度(χ2=6.713,P=0.010)以及颈部淋巴结转移(χ2=4.639,P=0.031)之间存在显著的相关性。单因素Log-rank检验分析显示,KRT4表达(χ2=23.962,P<0.001)、临床分期(χ2=4.621,P=0.032)、颈部淋巴结转移(χ2=7.549,P=0.006)与喉癌预后相关,Kaplan-Meier生存曲线提示KRT4阳性表达组的存活率明显高于KRT4阴性表达组。Cox回归模型研究发现KRT4表达是影响喉癌预后的独立危险因素。 结论 KRT4在喉癌组织中的表达水平明显低于癌旁正常黏膜组织、声带息肉组织,且KRT4表达与患者的临床分期、分化程度及颈部淋巴结的转移有关,KRT4阳性表达的喉癌患者预后更好。因此,KRT4有望成为一种重要的生物学指标,用以指导喉癌的诊断、治疗以及预后评估。
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[1] Baird BJ, Sung CK, Beadle BM, et al. Treatment of early-stage laryngeal cancer: a comparison of treatment options[J]. Oral Oncol, 2018, 87: 8-16. doi:10.1016/j.oraloncology.2018.09.012 [2] Obid R, Redlich M, Tomeh C. The treatment of laryngeal cancer[J]. Oral Maxillofac Surg Clin North Am, 2019, 31(1): 1-11. doi:10.1016/j.coms.2018.09.001 [3] 曾晶, 陈东妮, 徐进. 角蛋白与肿瘤[J]. 中国细胞生物学学报, 2012, 34(5): 485-492 [4] Moll R, Divo M, Langbein L. The human keratins: biology and pathology[J]. Histochem Cell Biol, 2008, 129(6): 705-733. doi:10.1007/s00418-008-0435-6 [5] Pan XO, Hobbs RP, Coulombe PA. The expanding significance of keratin intermediate filaments in normal and diseased epithelia[J]. Curr Opin Cell Biol, 2013, 25(1): 47-56. doi:10.1016/j.ceb.2012.10.018 [6] Toivola DM, Strnad P, Habtezion A, et al. Intermediate filaments take the heat as stress proteins[J]. Trends Cell Biol, 2010, 20(2): 79-91. doi:10.1016/j.tcb.2009.11.004 [7] Takikita M, Hu N, Shou JZ, et al. Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma[J]. Anticancer Res, 2011, 31(3): 945-952 [8] Sakamoto K, Aragaki T, Morita KI, et al. Down-regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis[J]. Histopathology, 2011, 58(4): 531-542. doi:10.1111/j.1365-2559.2011.03759.x [9] 黄沂传, 李鹏, 徐艳丽, 等. CK4与CK13在喉咽鳞状细胞癌中的表达及其临床意义[J]. 临床耳鼻咽喉头颈外科杂志, 2014(12): 874-877. doi: 10.13201/j.issn.1001-1781.2014.12.012 HUANG Yichuan, LI Peng, XU Yanli, et al. The expression of CK4, CK13in hypopharyngeal squamous cell carcinomas and its clinical significance[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2014(12): 874-877. doi: 10.13201/j.issn.1001-1781.2014.12.012 [10] 尹文华, 刘素琴, 陈志凌, 等. 细胞角蛋白4和细胞角蛋白13在鼻腔-鼻窦鳞状细胞癌中的表达及临床意义[J]. 中国耳鼻咽喉头颈外科, 2016, 23(2): 98-101. doi: 10.16066/j.1672-7002.2016.02.010 YIN Wenhua, LIU Suqin, CHEN Zhiling, et al. Expression and clinical significance of CK4, CK13 in sinonasal squamous cell carcinoma[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2016, 23(2): 98-101. doi: 10.16066/j.1672-7002.2016.02.010 [11] Escobar-Hoyos LF, Yang J, Zhu JW, et al. Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker[J]. Mod Pathol, 2014, 27(4): 621-630. doi:10.1038/modpathol.2013.166 [12] Micci F, Panagopoulos I, Haugom L, et al. Genomic aberration patterns and expression profiles of squamous cell carcinomas of the vulva[J]. Genes Chromosomes Cancer, 2013, 52(6): 551-563. doi:10.1002/gcc.22053 [13] Zahra A, Dong QD, Hall M, et al. Identification of potential bisphenol A(BPA)exposure biomarkers in ovarian cancer[J]. J Clin Med, 2021, 10(9): 1979. doi:10.3390/jcm10091979 [14] Wang N, Huang XY, Cheng JS. BIRC5 promotes cancer progression and predicts prognosis in laryngeal squamous cell carcinoma[J]. PeerJ, 2022, 10: e12871. doi:10.7717/peerj.12871 [15] Steuer CE, El-Deiry M, Parks JR, et al. An update on larynx cancer[J]. CA Cancer J Clin, 2017, 67(1): 31-50. doi:10.3322/caac.21386 [16] Gao W, Zhang YL, Niu M, et al. Identification of miR-145-5p-centered competing endogenous RNA network in laryngeal squamous cell carcinoma[J]. Proteomics, 2019, 19(21/22): e1900020. doi:10.1002/pmic.201900020 [17] 王媚, 李志海. 喉癌干细胞:克服多药耐药性的潜在治疗靶点[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 120-128. doi: 10.6040/j.issn.1673-3770.0.2021.388 WANG Mei, LI Zhihai. Laryngeal cancer stem cells: potential therapeutic targets for overcoming multidrug resistance[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 120-128. doi: 10.6040/j.issn.1673-3770.0.2021.388 [18] Karantza V. Keratins in health and cancer: more than mere epithelial cell markers[J]. Oncogene, 2011, 30(2): 127-138. doi:10.1038/onc.2010.456 [19] Bragulla HH, Homberger DG. Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia[J]. J Anat, 2009, 214(4): 516-559. doi:10.1111/j.1469-7580.2009.01066.x [20] Toivola DM, Boor P, Alam C, et al. Keratins in health and disease[J]. Curr Opin Cell Biol, 2015, 32: 73-81. doi:10.1016/j.ceb.2014.12.008 [21] Sharma P, Alsharif S, Fallatah A, et al. Intermediate filaments as effectors of cancer development and metastasis: a focus on keratins, vimentin, and nestin[J]. Cells, 2019, 8(5): 497. doi:10.3390/cells8050497 [22] Zhang JM, Quan JJ, Ren YY, et al. Keratin 4 regulates the development of human white sponge nevus[J]. J Oral Pathol Med, 2018, 47(6): 598-605. doi:10.1111/jop.12728 [23] Chung JY, Braunschweig T, Hu N, et al. A multiplex tissue immunoblotting assay for proteomic profiling: a pilot study of the normal to tumor transition of esophageal squamous cell carcinoma[J]. Cancer Epidemiol Biomarkers Prev, 2006, 15(7): 1403-1408. doi:10.1158/1055-9965.EPI-05-0651 [24] Xue LY, Hu N, Song YM, et al. Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma[J]. BMC Cancer, 2006, 6: 296. doi:10.1186/1471-2407-6-296 [25] Ye H, Yu TW, Temam S, et al. Transcriptomic dissection of tongue squamous cell carcinoma[J]. BMC Genomics, 2008, 9: 69. doi:10.1186/1471-2164-9-69 [26] Wang L, Ma X, Yu J, et al. Negative regulation of miR-1288-3p/KRT4 axis through a circular RNA in oral cancer[J]. J Biochem Mol Toxicol, 2022, 36(8): e23118. doi:10.1002/jbt.23118 |
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