CAJ | 학술논문

背景与目的：胸苷激酶1(thymidine kinase 1，TK1)在细胞分裂期的细胞质中表达，是将脱氧胸苷转换为胸苷酸的催化酶，是嘧啶补救途径的关键酶。本研究探讨TK1在乳腺肿瘤患者血清中的表达及其临床意义。方法：收集上海交通大学医学院附属瑞金医院乳腺疾病诊治中心145例乳腺癌患者(乳腺癌组)，55例乳腺纤维腺瘤患者(乳腺纤维腺瘤组)，采用化学发光斑点杂交法检测两组患者的血清TK1水平，并分析血清TK1水平与各个临床病理特征的关系。结果：乳腺癌组血清TK1水平为(2.749±0.122)pmol/L，乳腺纤维腺瘤组为(1.319±0.126)pmol/L，差异有统计学意义(P<0.0001)。在乳腺癌患者中，淋巴结晚期(P=0.049)、有远处转移(P=0.0031)、TNM分期晚期(P=0.01)的血清TK1水平明显升高。乳腺超声(P<0.001)，乳腺磁共振(P=0.005)，乳腺钼靶(P=0.032)BI-RADS分类为恶性(4C-6)的患者的TK1水平高于良性(0-4B)患者。雌激素受体高表达的乳腺癌患者的TK1水平高于低表达的患者(P=0.034)。在不同的年龄、分化程度、肿块大小及其他激素受体情况差异无统计学意义(P>0.05)。随访2年后未发现TK1水平与无进展生存期的相关性，差异无统计学意义(P=0.7061)。结论：血清TK1在乳腺癌的早期诊断，预测预后有重要价值，并可能成为新的分子靶向治疗的基础。
배경여목적：흉감격매1(thymidine kinase 1，TK1)재세포분렬기적세포질중표체，시장탈양흉감전환위흉감산적최화매，시밀정보구도경적관건매。본연구탐토TK1재유선종류환자혈청중적표체급기림상의의。방법：수집상해교통대학의학원부속서금의원유선질병진치중심145례유선암환자(유선암조)，55례유선섬유선류환자(유선섬유선류조)，채용화학발광반점잡교법검측량조환자적혈청TK1수평，병분석혈청TK1수평여각개림상병리특정적관계。결과：유선암조혈청TK1수평위(2.749±0.122)pmol/L，유선섬유선류조위(1.319±0.126)pmol/L，차이유통계학의의(P<0.0001)。재유선암환자중，림파결만기(P=0.049)、유원처전이(P=0.0031)、TNM분기만기(P=0.01)적혈청TK1수평명현승고。유선초성(P<0.001)，유선자공진(P=0.005)，유선목파(P=0.032)BI-RADS분류위악성(4C-6)적환자적TK1수평고우량성(0-4B)환자。자격소수체고표체적유선암환자적TK1수평고우저표체적환자(P=0.034)。재불동적년령、분화정도、종괴대소급기타격소수체정황차이무통계학의의(P>0.05)。수방2년후미발현TK1수평여무진전생존기적상관성，차이무통계학의의(P=0.7061)。결론：혈청TK1재유선암적조기진단，예측예후유중요개치，병가능성위신적분자파향치료적기출。
Background and purpose: The position of thymidine kinase 1 (TK1) expression during cell division is in the cytoplasm. It is a catalytic enzyme to convert deoxythymidine into thymidylate. It is the key enzyme of pyrimidine salvage pathway. The aim of this study was to analyze the serum expression level of TK1 in patients with breast cancer, and explore the application of serum TK1 test in clinical assessments of diagnosis, treatment and prognosis for breast cancer. Methods: Patient data were collected from the patients admitted in Comprehensive Breast Health Center at Rui Jin Hospital. Chemiluminesence dot blot assay was used to detect serum TK1 levels in 145 breast cancer patients and 55 patients with breast ifbroadenoma. The correlations of serum TK1 levels with breast tumor biological behavior was further studied. Results:Serum TK1 expression levels was signiifcantly increased in breast cancer patients [(2.749±0.122)pmol/L] when compared to breast fibroadenoma patients[(1.319±0.126)pmol/L, P<0.000 1]. Serum TK1 levels were statistically increased in patients with lymph node metastasis (P=0.049), distal metastasis (P=0.003 1), and late TNM stages (P=0.01). No serum TK1 level differences were found in patients with different ages (P>0.05), different tumor grades (P=0.453) and different tumor size (P=0.908). Preoperative imaging results including breast ultrasound, breast mammography and breast magnetic resonance were analyzed by assessments of BI-RADS category, and serum TK1 levels in patients with different BI-RADS categories were studied. Serum TK1 levels in patients with breast ultrasound BI-RADS categories 4C-6 were signiifcantly higher than those with category 0-4B (P<0.001). Consistently, the serum TK1 levels in patients with MR BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.005). The serum TK1 levels in patients with mammography BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.032). The serum TK1 levels were signiifcantly increased in patients with ER high expression in breast tumor tissues than those with low expression (P=0.034). Serum TK1 levels had no differences in patients with different expression levels of PR, HER-2 and MIB-1 (P>0.05). Most patients were followed up in our outpatient department for about 2 years. No progression-free survival differences were found in 2years. Conclusion:Serum TK1 test might be a potential tool for screening, prognosis determination and effect evaluations of targeted therapy in breast carcinoma.