血清胸苷激酶1对小细胞肺癌的诊断和疗效

发布时间：2018-11-20 12:05

【摘要】：背景:肺癌在临床上可分为非小细胞肺癌及小细胞肺癌。其中小细胞肺癌(SCLC)大约为肺癌总数的25%左右,其主要特点是恶性程度较高,临床上易转移,且早期转移比例较高并且呈广泛转移趋势,手术治疗效果差,但对化疗较敏感。目前临床上小细胞肺癌主要的化疗方案为顺铂或卡铂联合依托泊苷进行治疗,为业内公认的标准治疗模式。但是因其恶性程度高,增殖速度偏快,临床上易早期转移,很多患者临床发现时已经属于肺癌晚期,失去了最佳治疗时期,预后不良,生存率较低。因此临床上亟需一种能够早期筛查、监测疗效、预后判断的生物标志物。目前主要通过肿瘤标志物的筛查来提高早期肺癌的阳性诊断率,临床上广泛应用的检测指标主要有神经元特异性烯醇化酶(NES)、癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)、糖类抗原125(CA125)、胃泌素释放肽前体(Pro-GRP)等。尽管临床上对肺癌的早期诊断做了大量研究工作,早期阳性诊断率仍偏低。近年来,科学家及相关学者发现了一种新型的肿瘤标志物——细胞质胸苷激酶1(thymidine kinasel,TK1)。TK1与细胞增殖速度相关,对恶性肿瘤的诊断及疗效监测方面有着广泛的作用,具有非常重要的临床价值。目的:探讨血清TK1在小细胞肺癌早期诊断及化疗后疗效评估中价值。方法:选取2014年1月至2016年6月这段期间,安徽医科大学第一附院老年呼吸科的小细胞肺癌患者57例。病例中吸烟者为39例,不吸烟患者占18例,男性患者45例,女性患者12例。年龄在41至71岁之间,中位年龄在62岁。本次研究中广泛期患者占37例,局限期患者为20例。广泛期常指病灶扩散至上述区域以外;局限期定义为能被一个放射野所包围的病灶,常局限于一侧胸腔和局部淋巴结。所有患者临床上都确诊为小细胞肺癌,都采取依托泊苷+顺铂标准治疗方案,且所有患者不合并其他恶性肿瘤。临床上至少予以4个周期或以上的含铂类治疗方案,不能耐受顺铂的患者予以应用卡铂。同时收集同期住院患者57例为对照组,均为肺部良性疾病,不患有恶性肿瘤,其中男性22例,女性患者35例,年龄在17岁至75岁之间。上述所有患者都采用免疫印迹增强化学发光法对血清中胸苷激酶1的浓度予以测定,阳性结果的判定为TK12pmol/L。结果:TK1检测诊断小细胞肺癌的ROC曲线下面积为0.837,其灵敏度高于NSE;患者TK1的表达与小细胞肺癌临床分期(P=0.019)及化疗后疗效(P=0.000)有关,与性别、年龄、是否吸烟无显著相关(P0.05);TK1在治疗前小细胞肺癌中的水平明显高于对照组(P0.05),在化疗2个周期、4个周期的患者中其水平逐渐降低,组间差异有统计学意义(P0.05)。结论:TK1可作为小细胞肺癌患者的早期诊断及化疗疗效评估指标,在指导临床分期及预后判断上具有重要参考价值。
[Abstract]:Background: lung cancer can be divided into non-small cell lung cancer and small cell lung cancer clinically. The (SCLC) of small cell lung cancer is about 25% of the total number of lung cancer. Its main characteristics are high degree of malignancy, easy metastasis in clinic, high proportion of early metastasis and widespread metastasis trend, and the effect of surgical treatment is poor. But more sensitive to chemotherapy. At present, the main chemotherapy regimen for small cell lung cancer is cisplatin or carboplatin combined with etoposide. However, due to its high malignant degree, rapid proliferation, clinical easy to early metastasis, many patients have been found in the late stage of lung cancer, lost the best treatment period, poor prognosis, low survival rate. Therefore, a biomarker for early screening, monitoring of efficacy and prognosis is urgently needed. At present, the screening of tumor markers is mainly used to improve the positive diagnosis rate of early lung cancer. The commonly used markers in clinic are neuron-specific enolase (NES), carcinoembryonic antigen (CEA),). Cytokeratin 19 fragment (CYFRA21-1), carbohydrate antigen 125 (CA125), gastrin releasing peptide precursor (Pro-GRP) and so on. Although a great deal of research has been done on the early diagnosis of lung cancer, the early positive diagnosis rate is still low. In recent years, scientists and related scholars have discovered a new tumor marker, Cytoplasmic thymidine Kinase 1 (thymidine kinasel,TK1). TK1 is associated with cell proliferation speed, and has a wide range of roles in the diagnosis and monitoring of the curative effect of malignant tumors. It has very important clinical value. Objective: to evaluate the value of serum TK1 in early diagnosis of small cell lung cancer (SCLC). Methods: from January 2014 to June 2016, 57 patients with small cell lung cancer (SCLC) from the Department of Geriatrics and Respiratory Medicine of the first affiliated Hospital of Anhui Medical University were selected. There were 39 smokers, 18 non-smokers, 45 males and 12 females. The age ranged from 41 to 71, with a median age of 62. In this study, 37 patients with extensive stage, 20 patients with partial duration. The extensive stage usually refers to the lesion spreading beyond the above area, and the local term is defined as the lesion that can be surrounded by a radiation field, usually confined to one side of the thoracic cavity and local lymph nodes. All patients were diagnosed with small cell lung cancer (SCLC) and were treated with standard etoposide cisplatin regimen, and all patients were not associated with other malignant tumors. Patients who are not able to tolerate cisplatin are treated with carboplatin for at least 4 cycles or more. At the same time, 57 inpatients in the same period were collected as control group, all of them were benign pulmonary diseases without malignant tumor, including 22 males and 35 females, aged from 17 to 75 years old. All of the above patients were detected by Western blotting enhanced chemiluminescence assay for the concentration of thymidine kinase 1 in serum. The positive result was determined as TK12pmol/L.. Results: the area under the ROC curve of TK1 was 0.837, and its sensitivity was higher than that of NSE;. The expression of TK1 was related to the clinical stage of small cell lung cancer (P0. 019) and the curative effect after chemotherapy (P0. 000), but not to sex, age, smoking or not (P0.05). The level of TK1 in the small cell lung cancer before treatment was significantly higher than that in the control group (P0.05), in 2 cycles of chemotherapy, 4 cycles of patients their level gradually decreased, the difference between groups was statistically significant (P0.05). Conclusion: TK1 can be used as early diagnosis and evaluation index of chemotherapeutic effect in patients with small cell lung cancer, and it has important reference value in guiding clinical stage and prognosis.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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