Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2021, Vol. 35 ›› Issue (4): 64-69.doi: 10.6040/j.issn.1673-3770.0.2021.004

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Expression and clinical significance of the KCNK5 double-pore potassium channel protein in papillary thyroid carcinoma

XUE Gang1, SUN Xinmin1, LIN Xu2, WU Jingfang2   

  1. 1. Department of Otorhinolaryngology & Head and Neck Surgery, Hebei North University, Zhangjiakou 075000, Hebei, China;
    2. Department of Histology and Embryology, Hebei North University, Zhangjiakou 075000, Hebei, China
  • Published:2021-08-05

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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

CLC Number: 

  • R736.1
[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.
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