KCNK5双孔钾通道蛋白在甲状腺乳头状癌中的表达及临床意义

doi:10.6040/j.issn.1673-3770.0.2021.004

摘要/Abstract

摘要： 目的检测KCNK5在甲状腺乳头状癌(PTC)组织中的表达,探讨其与临床病理特征及患者预后的相关性。方法应用免疫组织化学和Western bloting方法检测PTC组织及癌旁正常组织中KCNK5表达,分析其与PTC临床病理特征的关系,KM Plotter数据库分析KCNK5与PTC预后的关系。结果免疫组化结果显示KCNK5表达于PTC细胞的胞膜、核膜和胞质,癌旁正常组织阴性或弱阳性;Western blot和免疫组化半定量积分显示PTC组织中的KCNK5水平显著高于癌旁正常组织(P<0.05)。KCNK5表达与PTC患者的TNM分期、淋巴结转移密切相关(均P<0.05);多因素Logistic回归分析进一步证实KCNK5与淋巴结转移密切相关(P<0.05)。Kaplan-Meier分析显示KCNK5高表达患者生存率明显低于KCNK5低表达患者(P<0.01)。结论 KCNK5与PTC患者淋巴结转移和预后密切相关,有望成为PTC评估预后的指标。

关键词: 甲状腺乳头状癌, 双孔钾通道, KCNK5, 免疫组织化学, Western bloting方法, KM Plotter数据库

Abstract: Objective To detect the expression of KCNK5 in papillary thyroid carcinoma(PTC)tissues and investigate its correlation with clinicopathological characteristics and prognosis in patients with PTC. Methods Immunohistochemistry and western blotting were used to detect the expression of KCNK5 in PTC tissues and paraneoplastic normal tissues, and the relationship between KCNK5 and the clinicopathological characteristics of PTC was analyzed; moreover, the relationship between KCNK5 and the prognosis of PTC was analyzed using the KM Plotter database. Results Immunohistochemical results showed that KCNK5 was expressed in the cytosol, nuclear membrane, and cytoplasm of PTC cells, and KCNK5 was either not expressed or weakly positively expressed in paraneoplastic normal tissues. Western blotting and immunohistochemical semi-quantitative integration showed that the expression level of KCNK5 in PTC tissues was significantly higher than that in paraneoplastic normal tissues(P<0.05). KCNK5 expression was positively correlated with TNM stage and lymph node metastasis in PTC patients(both P<0.05); multivariate logistic regression analysis further indicated that KCNK5 expression was related to lymph node metastasis(P<0.05). Kaplan-Meier analysis showed that the survival rate of patients with a high KCNK5 expression was significantly lower than that of patients with a low KCNK5 expression(P<0.01). Conclusion KCNK5 is closely associated with lymph node metastasis and prognosis of PTC patients and has the potential to become an indicator of PTC prognosis.

Key words: Papillary thyroid carcinoma, Two pore domain K⁺ channel, KCNK5, Immunohistochemistry, Western bloting, KM Plotter

中图分类号:

R736.1

薛刚,孙新民,林旭,吴靖芳. KCNK5双孔钾通道蛋白在甲状腺乳头状癌中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 64-69.

XUE Gang, SUN Xinmin, LIN Xu, WU Jingfang. Expression and clinical significance of the KCNK5 double-pore potassium channel protein in papillary thyroid carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(4): 64-69.

参考文献

[1] James BC, Mitchell JM, Jeon HD, et al. An update in international trends in incidence rates of thyroid cancer, 1973-2007[J]. Cancer Causes Control, 2018, 29(4/5): 465-473. doi:10.1007/s10552-018-1023-2.
[2] Ullmann TM, Gray KD, Moore MD, et al. Current controversies and future directions in the diagnosis and management of differentiated thyroid cancers[J]. Gland Surg, 2018, 7(5): 473-486. doi:10.21037/gs.2017.09.08.
[3] Nesovic-Ostojic J, Markovic-Lipkovski J, Todorovic J, et al. Immunolocalization of the TASK2 potassium channel in frog kidney[J]. Folia Biol(Krakow), 2016, 64(3): 183-188. doi:10.3409/fb64_3.183.
[4] Sepúlveda FV, Pablo Cid L, Teulon J, et al. Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K⁺-transport channels[J]. Physiol Rev, 2015, 95(1): 179-217. doi:10.1152/physrev.00016.2014.
[5] Pardo LA, Stühmer W. The roles of K(+)channels in cancer[J]. Nat Rev Cancer, 2014, 14(1): 39-48. doi:10.1038/nrc3635.
[6] Li WC, Xiong ZY, Huang PZ, et al. KCNK levels are prognostic and diagnostic markers for hepatocellular carcinoma[J]. Aging(Albany NY), 2019, 11(19): 8169-8182. doi:10.18632/aging.102311.
[7] Alvarez-Baron CP, Jonsson P, Thomas C, et al. The two-pore domain potassium channel KCNK5: induction by estrogen receptor alpha and role in proliferation of breast cancer cells[J]. Mol Endocrinol, 2011, 25(8): 1326-1336. doi:10.1210/me.2011-0045.
[8] 殷文娟, 李灵敏, 王丽, 等. BRAP在喉鳞状细胞癌中的表达及其与预后的相关性[J]. 临床耳鼻咽喉头颈外科杂志, 2019,33(11): 1081-1084. doi:10.13201/j.issn.1001-1781.2019.11.018. YIN Wenjuan, LI Lingmin, WANG Li, et al. Correlation between BRAP expression and prognosis of patients with laryngeal squamous cell carcinoma[J]. J Clin Otorhinolaryngol Head Neck Surg, 2019,33(11): 1081-1084. doi:10.13201/j.issn.1001-1781.2019.11.018.
[9] Nagy á, Lánczky A, Menyhárt O, et al. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets[J]. Sci Rep, 2018, 8(1): 9227. doi:10.1038/s41598-018-27521-y.
[10] Zhou YY, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J]. Nat Commun, 2019, 10(1): 1523. doi:10.1038/s41467-019-09234-6.
[11] Reyes R, Duprat F, Lesage F, et al. Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney[J]. J Biol Chem, 1998, 273(47): 30863-30869. doi:10.1074/jbc.273.47.30863.
[12] Bustos D, Bedoya M, Ramírez D, et al. Elucidating the structural basis of the intracellular pH sensing mechanism of TASK-2 K2P channels[J]. Int J Mol Sci, 2020, 21(2): E532. doi:10.3390/ijms21020532.
[13] Zhang P, Yang X, Yin Q, et al. Inhibition of SK4 potassium channels suppresses cell proliferation, migration and the epithelial-mesenchymal transition in triple-negative breast cancer cells[J]. PLoS One, 2016, 11(4): e0154471. doi:10.1371/journal.pone.0154471.
[14] Lin X, Wu JF, Wang DM, et al. The correlation and role analysis of KCNK2/4/5/15 in Human Papillary Thyroid Carcinoma microenvironment[J]. J Cancer, 2020, 11(17): 5162-5176. doi:10.7150/jca.45604.
[15] Dookeran KA, Zhang W, Stayner L, et al. Associations of two-pore domain potassium channels and triple negative breast cancer subtype in The Cancer Genome Atlas: systematic evaluation of gene expression and methylation[J]. BMC Res Notes, 2017, 10(1): 475. doi:10.1186/s13104-017-2777-4.
[16] Lin JD, Hsueh C, Chao TC. Long-term follow-up of the therapeutic outcomes for papillary thyroid carcinoma with distant metastasis[J]. Medicine(Madr), 2015, 94(26): e1063. doi:10.1097/md.0000000000001063.
[17] O'Hare Doig RL, Chiha W, Giacci MK, et al. Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma[J]. BMC Neurosci, 2017, 18(1): 62. doi:10.1186/s12868-017-0380-1.
[18] 宋晓宇,宋西成.缺氧诱导因子-1α 在甲状腺癌中的调节机制[J]. 山东大学耳鼻喉眼学报,2019,33(2):136-138. doi:10.6040/j.issn.1673-3770.0.2018.317. SONG Xiaoyu, SONG Xicheng. Research progress on the regulation of HIF-1α expression in thyroid carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019,33(2):136-138. doi:10.6040/j.issn.1673-3770.0.2018.317.
[19] Shin DH, Lin H, Zheng H, et al. HIF-1α-mediated upregulation of TASK-2 K+ channels augments Ca2⁺ signaling in mouse B cells under hypoxia[J]. J Imunol, 2014,193(10): 4924-4933. doi:10.4049/jimmunol.1301829.
[20] Endo K, Kito H, Tanaka R, et al. Possible contribution of inflammation-associated hypoxia to increased K2P5.1 k+ channel expression in CD4+ T cells of the mouse model for inflammatory bowel disease[J]. Int J Mol Sci, 2019, 21(1): 38. doi:10.3390/ijms21010038.

相关文章 15

[1]	李静静,武欣欣,毛宁,郑桂彬,牟亚魁,初同朋,贾传亮,郑海涛,米佳,宋西成. 基于CT影像组学诺模图术前预测甲状腺乳头状癌颈部中央区淋巴结转移的研究[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 51-59.
[2]	夏同良, 魏东敏, 钱晔, 李文明, 季炜, 潘新良, 雷大鹏. 累及喉、气管的甲状腺乳头状癌临床治疗分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 46-51.
[3]	郑桂彬, 张国军, 马驰, 韦树建, 孙海清, 吴国长, 郭雅文, 郑海涛, 宋西成. 经口腔前庭入路腔镜甲状腺手术在甲状腺乳头状癌中的安全效用分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 58-63.
[4]	黄乃思, 马奔, 官青, 王蕴珺, 魏文俊, 卢忠武, 杨舒雯, 徐伟博, 向俊, 嵇庆海, 王宇. 侧颈部淋巴结示踪技术在甲状腺癌手术治疗中的应用[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 69-74.
[5]	宁玉东, 蔡永聪, 孙荣昊, 姜健, 周雨秋, 税春燕, 汪旭, 郑王虎, 何天琪, 李超. 甲状腺乳头状癌前上纵隔淋巴结转移临床病理特征初步分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 120-124.
[6]	蒋宁宁,王鹏来,袁长勇,黄晓峰,蒋常委,刘宗响,孙铁忠. 肿瘤转移抑制蛋白在舌鳞状细胞癌中的表达与临床意义[J]. 山东大学耳鼻喉眼学报, 2019, 33(6): 64-67.
[7]	李浩,李延忠,王岩. HIF-1α、VEGF在阻塞性睡眠呼吸暂停低通气综合征患者[J]. 山东大学耳鼻喉眼学报, 2018, 32(2): 43-47.
[8]	安永明,穆文利,田艳勋,李伟,吴彦桥. 喉鳞癌组织中抑癌基因Maspin和转录因子Ets1的表达及意义[J]. 山东大学耳鼻喉眼学报, 2017, 31(3): 91-94.
[9]	李富, 赵书佑. 肺癌肿瘤抑制因子-1在喉鳞癌组织中的表达及其意义[J]. 山东大学耳鼻喉眼学报, 2015, 29(6): 36-38.
[10]	魏希建1，阴瑞兰2，郭星3. 增殖诱导配体在喉鳞状细胞癌中的表达[J]. 山东大学耳鼻喉眼学报, 2014, 28(1): 14-16.
[11]	徐禛1，于海玲1，刘冰2. 水通道蛋白-4在人鼻息肉组织中的表达及意义[J]. 山东大学耳鼻喉眼学报, 2014, 28(1): 48-50.
[12]	周鹏，贺青卿，庄大勇，范子义，郑鲁明，朱见，于芳，岳涛，董学峰. 甲状腺乳头状癌颈部淋巴结转移规律的临床分析[J]. 山东大学耳鼻喉眼学报, 2013, 27(6): 12-15.
[13]	钱晔，雷大鹏，金童，刘大昱，许风雷，潘新良. Slit2在喉咽鳞癌中的表达及其与LVD关系的研究[J]. 山东大学耳鼻喉眼学报, 2012, 26(5): 12-15.
[14]	沈斌，董频，英信江，高尚，李大伟. ABCG2及NF-κB p65在下咽癌中的表达意义[J]. 山东大学耳鼻喉眼学报, 2012, 26(4): 17-20.
[15]	王欣如1，2，刘志艳3，李丽珍1，黄涛2，夏斌4，李芳邻1，2. TGF-β1G-800A、C-509T单核苷酸基因多态性与甲状腺乳头状癌易感性的关系[J]. 山东大学耳鼻喉眼学报, 2012, 26(3): 28-32.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed