首页|钙激活钾通道蛋白4在甲状腺乳头状癌组织的表达及临床意义

钙激活钾通道蛋白4在甲状腺乳头状癌组织的表达及临床意义

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目的 探讨钙激活钾通道蛋白4(KCNN4)在甲状腺乳头状癌(PTC)中的表达情况、其与患者临床病例特征及预后的关系.方法 收集2021年1月至2021年6月在华中科技大学同济医学院附属同济医院甲状腺乳腺外科手术切除的PTC及癌旁甲状腺组织共116例,通过免疫组织化学实验检测KCNN4的表达水平,并分析不同KCNN4表达水平的患者之间的临床病例特征及预后的差异;通过细胞计数试剂盒(CCK-8)实验和划痕愈合实验检测KCNN4对PTC细胞增殖和迁移能力的影响.组间比较采用非配对t检验;KCNN4与患者临床病理特征的关系采用x2 检验或Fisher精确检验,生存分析采用Kalpan-Meier法.结果 KCNN4在PTC中的表达显著高于癌旁组织(免疫组织化学评分:8.17±2.46比3.26±0.72,t=8.44,P<0.05);KCNN4的表达与肿瘤多灶性情况[低表达比高表达(下同),单灶为31比50,多灶为6比29,x2=2.24,P<0.05]、肿瘤TNM分期(Ⅰ~Ⅱ期为35比60,Ⅲ~Ⅳ期为2比19,x2=2.43,P<0.05)及甲状腺外侵犯显著相关(无腺外侵犯为34比59,有腺外侵犯为3比20,x2=2.17,P<0.05),而与患者年龄(≤55岁为12比28,>55岁为25比51,x2=0.32,P>0.05)、性别(男为5比16,女为32比63,x2=0.88,P>0.05)、是否合并有桥本甲状腺炎无关(无桥本甲状腺为23比56,有桥本甲状腺炎为14比23,x2=0.94,P>0.05).KCNN4高表达患者的无复发生存率低于低表达组患者(复发率:8.86%比0%,HR=2.42,P<0.05);CCK-8实验表明,敲减KCNN4后的KTC-1和BCPAP细胞的增殖能力低于对照组细胞[KTC-1对照组比短发卡 RNA(shRNA)转染组,72 h:1.28±0.11 比 0.47±0.06,t=8.28,P<0.05;96 h:1.82±0.24 比0.61±0.10,t=10.45,P<0.05;BCPAP 对照组 比 shRNA 转染组,72 h:1.37±0.19 比 0.51±0.07,t=6.14,P<0.05;96 h:2.03±0.47 比 0.84±0.20,t=3.99,P<0.05].划痕愈合实验显示,敲降 KCNN4后的KTC-1和BCPAP细胞划痕愈合能力低于对照组细胞[KTC-1对照组比shRNA转染组24 h划痕愈合百分比:(66.47±7.60)%比(33.41±3.76)%,t=6.28,P<0.05;BCPAP 对照组 比 shRNA转染组24 h 划痕愈合百分比:(71.25±9.06)%比(43.32±5.83)%,t=12.10,P<0.05].结论 KCNN4与PTC发生、发展密切相关.
Expression and clinical significance of potassium calcium-activated channel subfamily N member 4 in papillary thyroid carcinoma
Objective To investigate the expression of potassium calcium-activated channel sub-family N member 4(KCNN4)in papillary thyroid carcinoma(PTC)and its association with clinical charac-teristics and prognosis.Methods Immunohistochemistry was performed to determine the expression level of KCNN64 in 116 cases of PTC and adjacent normal thyroid tissues collected from the Department of Thy-roid and Breast Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2021 to June 2021.The clinical characteristics and prognosis were analyzed a-mong patients with different levels of KCNN4 expression.Additionally,the impact of KCNN4 on PTC cell proliferation and migration was assessed using CCK-8 assay and wound healing assay.Unpaired t test was used for comparison between groups.The relationship between KCNN4 and clinicopathological characteris-tics of patients was analyzed by X2 test or Fisher exact test.Survival analysis was performed by Kalpan-Meier method.Results The expression of KCNN4 in PTC was significantly higher than that in adjacent tissues(immunohistochemical score:8.17±2.46 vs.3.26±0.72,t=8.44,P<0.05).The expression of KCNN4 was significantly correlated with tumor multifocality[low expression group vs.high expression group(the same below),31 vs.50 in single lesion,6 vs.29 in multiple lesions,x2=2.24,P<0.05],tumor TNM stage(Ⅰ-Ⅱ stage:35 vs.60,Ⅲ-Ⅳ stage:2 vs.19,x2=2.43,P<0.05)and extrathyroi-dal extension(without extrathyroidal extension:34 vs.59,with extrathyroidal extension:3 vs.20,x2=2.17,P<0.05),while irrelevantly correlated with age(≤ 55 years old:12 vs.28,>55 years old:25 vs.51,x2=0.32,P>0.05),gender(male:5 vs.16,female:32 vs.63,x2=0.88,P>0.05)and Hashimoto's thyroiditis(without Hashimoto's thyroiditis:23 vs.56,with Hashimoto's thyroiditis:x2=0.94,P>0.05).The recurrence-free survival rate of patients with high KCNN4 expression was lower than that of patients with low KCNN4 expression(recurrence rate:8.86%vs.0%,HR=2.42,P<0.05).CCK-8 assay showed the proliferation ability of KTC-1 and BCPAP cells after KCNN4 knockdown was lower than that of control cells[KTC-1 control group vs.short hairpin RNA(shRNA)transfection group,72 h:1.28±0.11 vs.0.47±0.06,t=8.28,P<0.05;96 h:1.82±0.24 vs.0.61±0.10,t=10.45,P<0.05;BCPAP control group vs.shRNA transfection group,72 h:1.37±0.19 vs.0.51±0.07,t=6.14,P<0.05;96h:2.03±0.47 vs.0.84±0.20,t=3.99,P<0.05].Wound healing assay showed the wound healing ability of KTC-1 and BCPAP cells after KCNN4 knockdown was lower than that of the control group[the percentage of wound healing at 24 h in KTC-1 control group vs.shRNA transfection group:(66.47±7.60)%vs.(33.41±3.76)%,t=6.28,P<0.05;the percentage of wound healing at 24 h in BCPAP control group vs.shRNA transfection group:(71.25±9.06)%vs.(43.32±5.83)%,t=12.10,P<0.05].Conclusion These findings suggested that KCNN4 plays a crucial role in the occur-rence and progression of PTC.

Potassium calcium-activated channel subfamily N member 4Papillary thyroid car-cinomaClinical characteristicsPrognosis

姜斌、李汉宁、逯超

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华中科技大学同济医学院附属同济医院甲状腺乳腺外科,武汉 430030

钙激活钾通道蛋白4 甲状腺乳头状癌 临床病例特征 预后

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(6)