血清肿瘤标志物在晚期食管鳞状细胞癌疗效评价和预后判定中的作用

 目的　探讨血清肿瘤标志物在晚期食管鳞状细胞癌（简称：鳞癌）中的表达及其在化疗疗效评价和预后判断中的意义。方法　测定50例晚期食管鳞癌患者一线化疗前后血清标志物的水平。按照实体瘤的疗效评价标准（RECIST标准）评效。通过建立受试者工作特性曲线（ROC曲线）求最佳临界值。用Kaplan-Meier法行生存分析。结果　50例患者治疗前的血清肿瘤标志物阳性率以细胞角蛋白19片段（CYFRA21-1）最高（44.0 %,22／50）;癌胚抗原（CEA）最低（22.0 %,11／50）。配对样本Wilcoxon 秩和检验示部分缓解（PR）组化疗后CYFRA21-1、鳞状上皮细胞癌抗原（SCC-Ag）下降,差异有统计学意义（Z＝3.181、2.389,P＝0.001、0.017）,进展（PD）组化疗后CYFRA21-1、SCC-Ag升高,差异有统计学意义（Z＝2.701、2.250,P＝0.007、0.024）,稳定（SD）组化疗前后SCC-Ag、CYFRA21-1差异无统计学意义（Z＝0.414、1.114,P＝0.679、0.265）。提示SCC-Ag、CYFRA21-1与影像学疗效评价具有一致性。ROC曲线显示化疗后CYFRA21-1较化疗前升高32 %,SCC-Ag升高38 %,可作为预测化疗疗效的最佳临界值,并与影像学评效具有较好的一致性。化疗后CYFRA21-1较化疗前升高>32 %和SCC-Ag较化疗前升高＞38 %为晚期食管鳞癌预后不良因素。结论　CYFRA21-1和SCC-Ag对晚期食管鳞癌的诊断、预测化疗疗效和预后有重要意义。     

血清肿瘤标志物在晚期食管鳞状细胞癌疗效评价和预后判定中的作用

目的 探讨血清肿瘤标志物在晚期食管鳞状细胞癌(简称:鳞癌)中的表达及其在化疗疗效评价和预后判断中的意义.方法 测定50例晚期食管鳞癌患者一线化疗前后血清标志物的水平.按照实体瘤的疗效评价标准(RECIST标准)评效.通过建立受试者工作特性曲线(ROC曲线)求最佳临界值.用Kaplan-Meier法行生存分析.结果 50例患者治疗前的血清肿瘤标志物阳性率以细胞角蛋白19片段(CYFRA21-1)最高(44.0%,22/50);癌胚抗原(CEA)最低(22.0%,11/50).配对样本Wilcoxon秩和检验示部分缓解(PR)组化疗后CYFRA21-1、鳞状上皮细胞癌抗原(SCC-Ag)下降,差异有统计学意义(Z=3.181、2.389,P=0.001、0.017),进展(PD)组化疗后CYFRA21-1、SCC-Ag升高,差异有统计学意义(Z=2.701、2.250,P=0.007、0.024),稳定(SD)组化疗前后SCC-Ag、CYFRA21-1差异无统计学意义(Z=0.414、1.114,P=0.679、0.265).提示SCC-Ag、CYFRA21-1与影像学疗效评价具有一致性.ROC曲线显示化疗后CYFRA21-1较化疗前升高32%,SCC-Ag升高38%,可作为预测化疗疗效的最佳临界值,并与影像学评效具有较好的一致性.化疗后CYFRA21-1较化疗前升高＞32%和SCC-Ag较化疗前升高＞38%为晚期食管鳞癌预后不良因素.结论 CYFRA21-1和SCC-Ag对晚期食管鳞癌的诊断、预测化疗疗效和预后有重要意义.     

血清肿瘤标志物在晚期食管鳞状细胞癌疗效评价和预后判定中的作用

目的 探讨血清肿瘤标志物在晚期食管鳞状细胞癌(简称:鳞癌)中的表达及其在化疗疗效评价和预后判断中的意义.方法 测定50例晚期食管鳞癌患者一线化疗前后血清标志物的水平.按照实体瘤的疗效评价标准(RECIST标准)评效.通过建立受试者工作特性曲线(ROC曲线)求最佳临界值.用Kaplan-Meier法行生存分析.结果 50例患者治疗前的血清肿瘤标志物阳性率以细胞角蛋白19片段(CYFRA21-1)最高(44.0%,22/50);癌胚抗原(CEA)最低(22.0%,11/50).配对样本Wilcoxon秩和检验示部分缓解(PR)组化疗后CYFRA21-1、鳞状上皮细胞癌抗原(SCC-Ag)下降,差异有统计学意义(Z=3.181、2.389,P=0.001、0.017),进展(PD)组化疗后CYFRA21-1、SCC-Ag升高,差异有统计学意义(Z=2.701、2.250,P=0.007、0.024),稳定(SD)组化疗前后SCC-Ag、CYFRA21-1差异无统计学意义(Z=0.414、1.114,P=0.679、0.265).提示SCC-Ag、CYFRA21-1与影像学疗效评价具有一致性.ROC曲线显示化疗后CYFRA21-1较化疗前升高32%,SCC-Ag升高38%,可作为预测化疗疗效的最佳临界值,并与影像学评效具有较好的一致性.化疗后CYFRA21-1较化疗前升高＞32%和SCC-Ag较化疗前升高＞38%为晚期食管鳞癌预后不良因素.结论 CYFRA21-1和SCC-Ag对晚期食管鳞癌的诊断、预测化疗疗效和预后有重要意义.     

Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma

The purpose of this study was to investigate clinical–biological factors which could predict the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). One hundred eighty-one patients with stages I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), albumin (A) as well as hemoglobin (HB) concentration were measured before the initiation of chemoradiotherapy (CRT). The cutoff values of CYFRA21-1, CEA, and A were defined as 3.4 ng/ml, 3.3 ng/ml, 3.5 g/dl, respectively. HB was divided into three levels: <12.0, 12.0–14.0, and >14.0 g/dl. Clinical factors such as sex, age, tumor location, primary cancer length, and tumor–node–metastasis stage were also evaluated. The effective rate (complete response + partial response) of the primary tumor estimated by computed tomography was 60.71% (17 out of 28) in patients with CEA high group while 92.54% (62 out of 67) in patients with CEA low group (P = 0.000) and 62.50% (20 out of 32) in patients with CYFRA21-1 high group while 92.98% (53 out of 57) in patients with CYFRA21-1 low group (P = 0.000). HB levels before and during CRT were also associated with the effectiveness (P = 0.005, 0.033, respectively). HB levels before CRT at 12.0–14.0 g/dl were associated with the best effectiveness, followed by >14.0 and <12.0 g/dl (effective rates 88.89% vs. 83.75%, 62.07%, respectively, P = 0.005). HB levels during CRT also showed similar results (effective rates 87.80% vs. 85.41%, 70.59%, respectively, P = 0.033). Furthermore, according to numbers of the above risk factors, the sensitivity of CRT was higher in patients with zero to one risk factors than those with two to four risk factors (P = 0.023). CYFRA21-1 and CEA as well as HB and their combination may be helpful in predicting the sensitivity to CRT of ESCC. However, the results should be further confirmed in larger, more homogeneous studies.     

食管鳞状细胞癌118例肿瘤标志物HSP90α联合Cyfra21-1和CEA检测临床意义

目的目前食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)尚缺乏灵敏度高的诊断标志物,大多数患者确诊时已到中晚期且预后不良。本研究探讨热休克蛋白90α(heat shock protein 90α,HSP90α)、细胞角蛋白片段19抗原21-1(cytokeratin fragment 19antigen 21-1,Cyfra21-1)和癌胚抗原(carcinoembryonic antigen,CEA)联合检测对ESCC患者的诊断价值及其临床意义。方法选取2016-01-06-2018-12-10山东省肿瘤医院血液采集时未接受放化疗及手术治疗的118例ESCC患者为研究对象并采集血样,同期收集33名健康体检者血液标本。采用酶联免疫吸附测定法检测血浆HSP90α表达水平,采用电化学发光法检测血清Cyfra21-1和CEA表达水平。ROC曲线评估3个指标单独或联合检测对ESCC的诊断效能,各指标表达与食管癌患者临床病理因素的关联分析采用χ^2检验。结果 ESCC患者中HSP90α、Cyfra21-1和CEA中位数(四分位间距)分别为62.535(45.190~107.708)、3.365(2.038~4.633)和3.545(2.190~5.000)ng/mL,均高于对照组的48.882(36.190~64.033)、1.970(1.590~2.380)和1.990(1.990~2.635)ng/mL,差异有统计学意义,Z值分别为-3.566、-4.131和-4.829,均P=0。ESCC患者中HSP90α、Cyfra21-1和CEA阳性表达与患者的肿瘤大小、远端转移及TNM分期,差异均有统计学意义,P<0.05。ESCCⅣ期患者HSP90α、Cyfra21-1及CEA表达水平高于Ⅲ期患者,差异有统计学意义,P<0.05。ESCC患者中HSP90α与Cyfra21-1、CEA联合检测双阳性率分别为31.36%和34.75%,表达呈正相关(r=0.23,P=0.012;r=0.397,P=0)。HSP90α与Cyfra21-1、CEA联合检测对ESCC患者的诊断灵敏度为78.0%,特异性为72.8%,曲线下面积为0.862。结论肿瘤标志物HSP90α和Cyfra21-1、CEA在ESCC患者中呈现高表达状况,联合检测能够提高ESCC患者的诊断灵敏性和特异性,3种肿瘤标志物联合检测对于ESCC早期诊断与评估分期有一定价值。     

Serum Sialyl Lewis x and cytokeratin 19 fragment as predictive factors for recurrence in patients with stage I non-small cell lung cancer

This study aimed to establish the clinical significance of preoperative serum cytokeratin 19 fragment (CYFRA21-1) and Sialyl Lewis(x) (SLX) in patients with stage I non-small cell lung cancer (NSCLC). The study involved 137 patients (87 male, 50 female; median age 69 years) with completely resected stage I NSCLC. SLX, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA21-1 were examined. Receiver operator characteristic (ROC) curves were constructed to determine prognostic cut-off values. Among the 137 patients, we identified 30 with recurrence within 3 years. The 5-year survival rates in patients with (n=30) and without (n=107) recurrence were 14% and 81%, respectively. The serum concentrations of SLX, CEA, and CYFRA21-1 in the recurrence group were significantly higher than those in the non-recurrence group. The areas under the ROC curve (AUC) were 0.72, 0.65, 0.53, and 0.64 for SLX, CEA, SCC, and CYFRA21-1, respectively. The prognostic cut-off values were 36U/ml, 7.8ng/ml, 1.5ng/ml, and 3.2ng/ml for SLX, CEA, SCC, and CYFRA21-1, respectively. A log-rank test revealed that age, performance status, T factor, lymphatic invasion, vascular invasion, SLX, CEA, SCC, and CYFRA21-1 were all significantly associated with survival. By multivariate analysis, age, performance status, lymphatic invasion, SLX (risk ratio, 4.11) and CYFRA21-1 (risk ratio, 3.47) were independent prognostic factors. For patients positive for both CYFRA21-1 and SLX, the relative risk was 5.32 compared with patients who were negative for both markers. The 5-year survival rates were 80% in the group negative for both markers (n=86); 52% in the group positive for one of the markers (n=43); and 13% for the group positive for both markers (n=8) (p<0.001). We concluded that serum SLX and CYFRA21-1 were prognostic markers for stage I NSCLC. Their combination should contribute to the classification of stage I NSCLC patients. There is a need to consider adjuvant and neoadjuvant therapies to improve prognosis in patients positive for both tumor markers.     

食管癌放疗前后多种生物标志物联合检测的临床意义

目的通过检测食管癌放疗前后血清肿瘤标志物癌胚抗原（CEA）、鳞状上皮细胞癌相关抗原（SCC）和细胞角化素蛋白片段19（CYFRA21—1）水平的变化,探讨食管癌放疗前后多种生物标志物联合检测的临床意义。方法收集初治食管癌患者226例,采用酶联免疫吸附法检测放疗前后食管癌患者血清CEA、SCC和CYFRA21-1水平,通过SPSS13．0软件进行统计学处理。结果226例食管癌患者放疗前CEA、SCC和CYFRA21—1的阳性率分别为11．1％、16．8％、27．4％,联合检测阳性率39．8％。病变长度愈长,病期愈晚,肿瘤浸润愈深,CEA、SCC、CYFRA21—1血清总体平均水平愈高,早期患者水平较低。三者中CEA和CYFRA21—1的个体差异较大,CYFRA21—1与食管癌病理分期、放疗疗效相关性最好。90例阳性患者放疗后76．7％的患者标志物水平下降至正常值。结论血清CEA、SCC、CYFRA21—1联合检测可用于食管癌的辅助诊断,对疗效和预后判断有较好的临床应用价值。     

组织多肽抗原联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊治中的价值

目的 评估组织多肽抗原（TPA）联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊断与疗效监测中的应用价值。方法 用化学发光法和电化学发光法检测238例肺癌患者、25例肺部良性疾病患者及65名健康对照者血清中的TPA、ProGRP、NSE、SCC、CYFRA21-1和CEA水平,并对33例肺癌患者进行随访检测。同时用SPSS19.0统计软件及接受器工作性能曲线（ROC）分析,评价肿瘤标志物的临床应用价值。结果 肺癌患者血清TPA水平（中位数为130.45 U/L）明显高于肺部良性疾病患者（中位数为82.21 U/L）和健康对照组（中位数为70.96 U/L）（P=0.000, 0.002）。根据ROC曲线分析,TPA检测肺癌的临界值为130 U/L,敏感度为50%,特异性为88.9%,相比于其他肺癌标志物( ProGRP、NSE、SCC、CYFRA21-1、CEA）,敏感度较高,特异性稍低。肺癌患者血清TPA水平及阳性率随着肿瘤分期的升高而升高（P均<0.05）。TPA水平与疗效也密切相关,临床治疗有效时TPA下降,而病情恶化或出现转移时则升高。各种组合检测中,以六项组合诊断肺癌的敏感度和有效性最高。结论 TPA联合ProGRP、CEA、NSE、SCC、CYFRA21-1测定在肺癌的诊断、疗效及监测复发转移中,具有一定的临床价值。     

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer

BACKGROUND: The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS: One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (> or =20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS: CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC.     

常用血清肿瘤标志物在可手术肺癌患者预后中的价值

目的 探讨血清CEA、CA125、CA199、NSE、CYFRA21-1和SCC-Ag水平在评估非小细胞肺癌根治手术后的预后价值,以期合理选择术前的检验指标。方法 收集1 851例行肺癌根治手术的患者术前血清肿瘤标志物的检验值、临床病理和随访信息,进行差异及生存分析。结果 CEA、CA125、CA199、CYFRA21-1和SCC-Ag的阳性率在不同病理分期中差异有统计学意义（P<0.001）,Ⅱ和Ⅲ期的患者阳性率明显高于Ⅰ期患者,而NSE差异无统计学意义（P=0.743）。CEA、CA125、CA199、CYFRA21-1阴性组患者的生存率显著高于阳性组（P<0.05）。NSE阴性的患者远期生存率劣于阳性组患者（P=0.033）。SCC-Ag阳性与阴性患者的远期生存率差异无统计学意义（P=0.072）。Cox回归比例风险模型分析发现CEA（HR=1.572, 95%CI: 1.117~2.214, P=0.010）、CA125（HR=2.464, 95%CI:1.610~3.772, P<0.001）和CYFRA21-1（HR=1.445, 95%CI: 1.044~2.000, P=0.027）是评价非小细胞肺癌手术预后的独立危险因素。结论 CEA、CA125和CYFRA21-1在评价非小细胞肺癌手术预后方面有良好的应用价值,而CA199、NSE和SCC-Ag等指标价值有限。     

非小细胞肺癌患者血清多项肿瘤标志联合检测的临床意义

目的:评价癌胚抗原(CEA)、鳞状细胞癌相关抗原(SCC-Ag)、细胞角蛋白21-1片段(CYFRA21-1)、糖类抗原125(CA125)、糖类抗原153(CA153)和神经元特异性烯醇华酶(NSE)等6项标志联合检测,在非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床诊断、预后及评价疗效等方面的临床意义。方法:收集284例NSCLC患者的临床资料及肿瘤标志水平,评价标志水平与病情的关系。统计学分析采用SPSS10.0软件,用Kaplan-Merier法计算生存率和无肿瘤生存率,用Log-rank法进行差异检验,对单因素分析中P<0.3的预后因素使用Cox比例风险回归进行多因素分析。结果:肿瘤标志CEA的总阳性率为42.6%,CYFRA21-1为54.2%,SCC为12.6%,CA125为51.8%,CA153为39.4%,NSE为16.5%。6项标志联合检查的总阳性率为80.3%。CEA、CA153阳性患者的化疗疗效较差,而NSE阳性患者的化疗疗效较好。出现转移或病情进展的患者中,73.1%出现阴性标志和(或)经治疗已转为阴性的标志转为阳性。全组患者的中位无病生存期为12.98(2~22)个月,中位生存期为17.69(6~22)个月。结论:CEA、SCC-Ag、CYFRA21-1、CA125、CA153和NSE等6项标志在NSCLC患者中有较高的阳性率。多项标志联合检测的阳性率远高于任一标志单独检测的阳性率。     

Decline of serum CYFRA21-1 during chemoradiotherapy of NSCLC: a probable predictive factor for tumor response

We investigated the predictive value of decline in the serum levels of tumor markers on tumor response during the chemoradiotherapy (CRT) in patients with non-small cell lung cancer (NSCLC). The serum levels of cytokeratin 19 fragment antigen 21–1 (CYFRA21-1), neurone-specific enolase and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assays, while the tumor responses were assessed according to the World Health Organization response criteria. The relationship between the changes of serum level of tumor markers and the radiologic response were analyzed. The effective rates (CR + PR) in CYFRA21-1 (pretreatment serum level) high and low groups were 45.8% (33/72) and 66.7% (24/36), respectively (p = 0.032). Independent sample t test showed that the relationship between the response of CYFRA21-1 and the radiologic objective response are significantly different (p = 0.008). The best cutoff value of the decline ratio of CYFRA21-1 was established as 18.48% by ROC curve. CYFRA 21–1 responses appeared to be reliable surrogate markers to predict chemoradiotherapy efficacy in patients with NSCLC, an average drop of 18.48% in serum CYFRA21-1 appears to provide the predictive information for the sensitivity of CRT.     

食管鳞癌新辅助放化疗后复发风险分层分析

目的 探讨胸段食管鳞癌新辅助放化疗联合手术治疗后的复发风险模式,并分析术后病理分期与复发风险之间的关系。方法 回顾分析2002-2015年郑州大学附属肿瘤医院及中山大学肿瘤防治中心收治的174例局部晚期胸段食管鳞癌患者的病历资料。全组患者均采用术前同期放化疗联合手术治疗,化疗采用以铂类为基础的化疗方案,放疗剂量为40.0~50.4 Gy,常规分割。采用Kaplan-Meier法计算生存率,Logrank检验差异,Cox模型多因素分析。结果 中位随访时间为53.9个月,新辅助放化疗后病理完全缓解率为44.8%,其中59例(33.9%)患者复发。术后病理分期为0/Ⅰ、Ⅱ、Ⅲ期患者复发率分别为22.2%、38.7%、68.2%(P=0.000),疗后5年无复发生存率分别为74.7%、61.4%、20.9%(P=0.000)。20.5%的0/Ⅰ期或Ⅱ期患者的复发时间在术后3年以上,而Ⅲ期患者的复发时间均在2年以内。多因素分析结果显示年龄、临床分期、化疗方案、放化疗相关病理反应是影响无复发生存的因素(P=0.027、0.047、0.010、0.005)。结论 胸段食管鳞癌新辅助放化疗后的病理分期与复发风险密切相关,临床医生可根据不同的病理分期制定个体化的随访监测策略。     

Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma

BACKGROUND: The search for new tumor markers for breast carcinoma has been an area of vigorous study; nonetheless, to the authors' knowledge little new information has emerged beyond the clinical usefulness of CA 15-3. The authors studied serum CYFRA 21-1 in breast carcinoma based on evidence that breast carcinoma expresses cytokeratin 19 fragments and that CYFRA 21-1 is a specific antigen for cytokeratin 19 fragments. METHODS: The serum samples of 86 patients with primary breast carcinoma, 14 patients with recurrent breast carcinoma, 22 patients with benign mammary disease, and 25 healthy controls were provided for measurements of CYFRA 21-1, carcinoembryonic antigen (CEA), and CA 15-3. The relation between clinicopathologic features, prognosis, and disease free survival with serum CYFRA 21-1 titers was studied. RESULTS: There was no difference between the serum CYFRA 21-1 titers from patients with benign mammary disease and those from healthy controls. The sensitivities of CYFRA 21-1 for patients with International Union Against Cancer Stage IV and recurrent tumors were 60% and 64.2%, respectively, which were as high as those for CA 15-3 and superior to those for CEA. The hematogenous recurrence showed a very high sensitivity of 89%. According to the increments of T, N, and M factor numbers, the serum CYFRA 21-1 titers were elevated. No correlation between CYFRA 21-1 and CEA was observed and the correlation between CYFRA 21-1 and CA 15-3 was weak. The univariate and multivariate analyses for survival revealed that serum CYFRA 21-1 levels were an independent indicator of prognosis. CONCLUSIONS: The measurement of the serum CYFRA 21-1 titer in patients with breast carcinoma may be useful in monitoring for recurrence and evaluating the therapeutic effect in patients with advanced disease.     

肺癌患者血清肿瘤标志物与凝血功能变化相关性研究

目的:探讨肺癌患者血清肿瘤标志物和血浆凝血功能变化的相关性及其临床意义。方法:对157例肺癌患者、56例良性肺疾病患者和40例健康人进行回顾性研究,检测血清癌胚抗原（CEA）、神经元特异烯醇化酶（NSE）、细胞角蛋白19片段（CYFRA21-1)以及血浆纤维蛋白原（FIB）、D-二聚体（D-D）、血小板（PLT）,并对检测结果进行统计学分析。结果:肺癌组CEA、NSE、CYFRA21-1、FIB、D-D、PLT水平分别与良性肺疾病组和健康对照组比较差异均有统计学意义(P＜0.05)。肺癌组各指标水平在高分期（III/IV）组中均高于低分期(I+II)组(P＜0.05),除了PLT水平在肺癌高分期（III/IV）组与低分期(I+II)组比较差异无统计学意义（P＞0.05）。CYFRA21-1水平在IVb期肺癌组中高于IVa期组,差异有统计学意义（P＜0.05）;FIB水平与CYFRA21-1以及D-D分别与CEA、NSE、CYFRA21-1呈正相关;CEA对于肺癌诊断敏感性和特异性均最高,六项指标联合检测对肺癌诊断的敏感性(89.2%)和阴性预测值（64.6%）及对于非小细胞肺癌（NSCLC）诊断的曲线下面积（0.832）,均高于任一单项指标检测。结论:联合检测肿瘤标志物和凝血功能变化对肺癌早期诊断和治疗有重要价值,以及有助于预测肺癌患者血栓形成风险,给予早期预防有重要的指导意义。     

肺腺癌患者表皮生长因子受体基因突变与肿瘤标志物关系研究

目的  探讨肺腺癌患者表皮生长因子受体（EGFR）基因突变与血清肿瘤标志物之间的关系。 方法  选择2015年1月至2017年12月,中国医科大学附属第四医院胸外科肺腺癌患者资料97例。采用化学发光免疫法检测患者血清各肿瘤标志物水平,并对检测结果进行统计学分析。 结果  女性患者EGFR基因突变率高于男性患者,非吸烟患者高于吸烟患者,差异有统计学意义（均P＜0001）。而年龄、肿瘤分期对EGFR基因突变率无影响,差异无统计学意义（P＞005）。血清癌胚抗原（CEA）水平异常组EGFR基因突变率高于正常组,差异有统计学意义（P＜005）;当50 μg／L＜CEA＜100 μg／L时,EGFR基因突变率最高（77％）。血清细胞角蛋白19片段（CYFRA21 1）浓度,正常组患者EGFR基因突变发生率高于异常组,差异有统计学意义（P＜005）,而神经元特异性烯醇化酶（NSE）、CA125、CA153和CA19 9正常组与对应的异常组EGFR基因突变率差异无统计学意义（P＞005）。ROC曲线显示,血清CEA、CYFRA21 1水平预测EGFR基因突变的曲线下面积分别为0740、0609。 结论  肺腺癌患者女性、非吸烟患者更容易发生EGFR基因突变,血清肿瘤标志物CEA 、CYFRA21 1水平对预测EGFR基因突变有一定价值。     

血清肿瘤标志物在肺癌诊断中的应用价值*

目的:探讨SCC 、NSE、CEA 、CYFRA21-1 四项肿瘤标志物联合检测对肺癌的诊断价值。方法:采用化学发光法对肺癌组132 例、肺良性疾病组48例和正常对照组92例的血清SCC 、NSE 、CEA 、CYFRA21-1 四项肿瘤标志物进行检测及统计学分析。结果:NSE 、CEA 、CYFRA21-1 在肺癌组显著高于肺良性疾病组和正常对照组,SCC 肺癌组高于正常对照组,CEA 和CYFRA21-1肺良性疾病组显著高于正常对照组。CEA 在肺腺癌中的水平较高,NSE 在小细胞肺癌中的水平较高,而SCC 、CYFRA21-1 在肺鳞癌中的水平较高。单项肿瘤标志物在肺癌诊断中敏感性:NSE>CEA>CYFRA 21-1>SCC;在腺癌中CEA 敏感性最高（58.8%）,鳞癌中CYFRA21-1 敏感性最高（71.4%）,小细胞肺癌中NSE 敏感性最高（50.0%）。 NSE 、CEA 、CYFRA21-1 的ROC 曲线下面积分别为0.928 ± 0.034、0.957 ± 0.026、0.964 ± 0.023,显示诊断准确性较高。SCC 曲线下面积虽然大于0.5,但差异无统计学意义。肿瘤标志物联合检测,可以提高诊断试验的敏感性,在肺癌诊断中NSE 、CEA 、CYFRA21-1 组合敏感性最高（75.6%）,特异性也较好（90.7%）;腺癌诊断中SCC 、NSE 、CEA 组合敏感性最高（73.5%）,鳞癌诊断中NSE 、CEA 、CYFRA21-1 组合敏感性最高（75.8%）,小细胞肺癌中SCC 、NSE 、CYFRA21-1 组合敏感性最高（75.0%）。 结论:SCC 、NSE 、CEA 、CYFRA21-1 对肺癌的诊断均有一定意义,不同病理类型各有特点,选择合适的组合有利于对肺癌的鉴别诊断。      

Expression and Clinical Significance of miR-152 and CYFRA21-1 in Ovarian Cancer Tissues

To investigate the expression and clinical significance of miR-152 and CYFRA21-1 in ovarian cancer (OC) tissues. Seventy-four OC patients diagnosed in our hospital from March 2016 to April 2019 (research group, RG) and 30 patients with benign ovarian tumor at the same time (control group, CG) were collected as research objects in this experiment. qRT-PCR and ELISA were used to detect and observe the expression levels of miR-152 in patient tissues and CYFRA21-1 in serum. ROC curves were drawn to analyze the diagnostic value of miR-152 and CYFRA21-1 in OC. The clinicopathological correlation analysis was observed, Pearson was used to examine the correlation between the expression levels of miR- 152 and CYFRA21-1 and carcinoembryonic antigen (CEA), and the 3-year survival rate of patients was observed according to the high and low expression of miR-152 and CYFRA21-1. qRT-PCR and ELISA showed that the miR-152 expression in the RG was dramatically lower than that in the CG, while CYFRA21-1 (μg/L) was remarkably higher than that in the CG (p < 0.05). ROC was drawn based on the miR- 152 and CYFRA21-1 expression levels. The area under miR-152 curve was 0.724 (p < 0.05), and the area under CYFRA21-1 curve was 0.714 (p < 0.05). The expression levels of miR-152 and CYFRA21-1 were relevant to lymph metastasis, differentiation degree and pathological stage of OC patients (p < 0.05). Pearson test analysis identified that miR-152 and CYFRA21-1 were positively correlated with CEA (p < 0.001). The 3-year overall survival rate of miR-152 Low Expression Group (LEG) was 61.54%, that of high expression group (HEG) was 84.85%, that of CYFRA21-1 LEG was 83.75%, and that of HEG was 60.54%. miR-152 shows low expression in the tissues of patients and CYFRA21-1 shows high expression in serum, and both indexes have good diagnostic efficacy. The higher the miR-152 expression is, the higher the survival rate is, while the higher the CYFRA21-1 expression is, the lower the survival rate is.     

Preliminary Evaluation of Clinical Utility of CYFRA 21-1, CA 72-4, NSE,CA19-9 and CEA in Stomach Cancer

Background: Although various tumor markers have been utilized in management of stomach cancer (SC), only a few reports have described relevance of examples such as CYFRA 21-1 and neuron-specific enolase (NSE). The purpose of this study was to evaluate the potential diagnostic performance of  carcinoembryonic antigen (CEA), CA 19-9, CA72-4, CYFRA 21-1 and NSE in patients with SC. Materials and Methods: Ninety-six SC patients with pathologic confirmation between 2012 and 2013 were enrolled. Serum levels of five tumor markers were analyzed using a solid-phase immunoradiometric assay. Receiver operating characteristic (ROC) curves were plotted for the five tumor markers to investigate their diagnostic powers and adjusted cutoff values derived from analysis of ROC curves were evaluated to calculate the sensitivity of each for SC with recommended cutoff values. Results: Based on two different cutoff values (recommended and adjusted), CYFRA 21-1 (≥2.0 and 1.2 ng/ml) had a respective sensitivity of 50% and 78.1%, compared with 8.3% and 18.8% for CEA (≥7.0 and 3.9ng/ml), 15.6% and 18.8% for CA 19-9 (≥37 and 26.7 ng/ml), 28.1% and 9.6% for CA 72-4 (≥4.0 and 13 ng/ml) and 7.3% and 7.3% for NSE (≥14.7 and 15.0 ng/ml) in the initial staging of primary SC. The area under the curve (AUC) for CYFRA 21-1, with a value of 0.978 (95% confidence interval, 0.964-0.991) was comparativelythe highest. Univariate analysis revealed significant relationships between tumor marker level and lymph node involvement, metastasis and staging with CYFRA 21-1, CA 72-4 and NSE. Conclusions: CYFRA 21-1 was the most sensitive tumor marker and showed the most powerful diagnostic performance among the five SC tumor markers. NSE and CA 72-4 are significantly related to lymph node involvement, metastasis or stage. Further evaluations are warranted to clarify the clinical usefulness and prognostic prediction of these markers in SC.     

5种肿瘤标志物联合检测在口腔鳞状细胞癌中的诊断价值

目的:通过检测血清肿瘤标志物（SCC-Ag、CYFRA21-1、CEA、CA125、NSE）探讨联合检测对口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的临床诊断意义及诊断效能。方法:收集2015年1月至2018年1月就诊于新疆维吾尔自治区人民医院口腔颌面外科的OSCC患者60例,非OSCC恶性肿瘤患者60例,同期健康体检者60例作为正常组,均抽取空腹外周血2 ml,检测SCC-Ag、CYFRA21-1、CEA、CA125、NSE浓度。结果:OSCC患者的5种血清肿瘤标志物水平与非OSCC恶性肿瘤组、正常组比较差异具有统计学意义(P<0.05)。将CEA、CA125、SCC-Ag、CYFRA21-1、NSE联合检测后敏感性、特异性、准确性、阳性预测值均显著提高。结论:SCC-Ag、CYFRA21-1、CEA、CA125、NSE 5种肿瘤标志物在OSCC中联合检测可以显著提高诊断效能;5种肿瘤标志物的血清表达量在OSCC的临床诊断中具有一定的价值。