CEA、CA199及中性粒细胞与淋巴细胞比值在Ⅱ、Ⅲ期结直肠癌患者中的临床意义

发布时间：2018-04-22 08:38

本文选题：CEA + CA199　；参考：《大连医科大学》2017年硕士论文

【摘要】：背景与目的:在全球范围内消化系统的恶性肿瘤中,结直肠癌的发病率极高,死亡率也居高不下。早期的研究确认了 CEA在结直肠癌中预测预后、辅助分期及随访中的价值。CA199固然在结直肠癌中得到了普遍的临床应用,但其在结直肠癌中的辅助分期及展望预后等方面的价值存在分歧。近年来,国内外研究发现炎症在多种肿瘤的发生及转移中发挥关键作用,而中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyteratio,NLR)被证实可以作为炎症反应的替代标志物,已被多篇文献报道与结直肠癌的诊断、分期及预后密切相关。本研究将对CEA、CA199及NLR和Ⅱ、Ⅲ期结直肠癌患者的关系进行进一步探讨,以期为结直肠癌患者的精准诊治及随访监测提供更为科学的临床指导依据和理论基础。方法:一.研究对象:对我院2001年11月20日-2011年11月20日期间行根治术并经组织病理学证明为Ⅱ、Ⅲ期的结直肠癌患者共144例进行回顾性分析,收集其完整的临床病理学参数及随访资料,并进行统计和分析。二.血清标本收集1.收集患者术前1周内及术后1个月内化放疗前的肿瘤标记物指标癌胚抗原(CEA)和糖链抗原199(CA199),同时收集血常规指标中性粒细胞计数(N)及淋巴细胞计数(L),NLR的值通过中性粒细胞计数除以淋巴细胞计数获得。所获取的全部实验室指标均在术前1周内及术后1个月内未接受过化放疗、未使用升白细胞药物或其他免疫药物下测得,所有患者均无急慢性炎症、急性损伤、血液及免疫系统相关的疾病。2.根据我院的参考值范围设定如下:CEA5.0ng/ml定义为正常;CA19927.0U/ml定义为正常;中性粒细胞计数正常值的参考范围为(2.0-7.0)× 109/L、淋巴细胞计数正常值的参考范围为(0.8-4.0)× 109/L。三.随访采取电子病历或电话的方式对每个患者随访,随访时间截止到2016年11月20日。无病生存期(Disease-free survival,DFS)的定义是指从手术之日起至疾病局部复发、远处转移或由于任何原因导致死亡的时间。总生存期(Overall survival,OS)的定义是指从手术之日起至任何原因引起的死亡或最后一次随访日期的时间。四.统计学方法使用SPSS20.0软件版本对数据进行统计学分析,通过绘制受试者工作特征(Receiver operating characteristic,ROC)曲线来计算曲线下面积(Area under the curve,AUC),并通过计算约登指数(Youden index,YI)来确定NLR的最佳截断值。使用Pearson x 2检验或Fishier精确概率法分析CEA、CA199及NLR与各临床病理学参数之间的相关性。生存曲线的绘制和生存率的计算采取Kaplan-Meier方法,患者生存的单因素分析采取Log-rank检验,采用COX回归模型对单因素分析中P0.05者进行多因素分析评估独立预后因子,以P0.05被认为差异有统计学意义。结果:一.CEA、CA199及NLR与临床病理学参数之间的关系术前CEA、CA199及NLR与年龄、性别、肿块大小、肿瘤位置、分化程度、病理类型、TNM分期、T分期及N分期均无相关性,P0.05。但随着TNM分期的增加,术前CEA的值有增加的趋势(P=0.085),随着N分期的增加,术前CEA的值也有增加的趋势(P=0.090)。二.CEA、CA199及NLR对结直肠癌患者3年DFS率及5年OS率的影响(一)单因素分析显示,手术前后CEA、CA199及NLR的水平均是影响结直肠癌患者3年DFS率及5年OS率的相关因素(p0.05),此外TNM分期及N分期也是影响结直肠癌患者3年DFS率及5年OS率的相关因素(p0.05)。而年龄、性别、肿块大小、肿瘤位置、病理类型及T分期对结直肠癌患者3年DFS率及5年OS率均没有影响(p0.05)。分化程度是影响结直肠癌患者5年OS率的相关因素(p=0.015),对3年DFS率没有影响(p=0.085)。治疗方式是影响结直肠癌患者3年DFS率的相关因素(p=0.019),对5年OS率没有影响(p=0.194)。(二)多因素分析显示,手术前后NLR是结直肠癌患者3年DFS率及5年OS率的独立预后因素。此外,分化程度也是结直肠癌患者5年OS率的独立预后因素。三.由TNM分期分层中CEA、CA199及NLR对结直肠癌患者3年DFS率及5年OS率的影响(一)Ⅱ期患者中,术前CEA高低对3年DFS率没有影响,P0.05,组间比较无统计学差异;术前高CEA组对比低CEA组5年OS率明显降低,P=0.024,组间比较有统计学差异。术后高CEA组对比低CEA组3年DFS率及5年OS率均明显降低,P值分别为0.001和0.002,组间比较有统计学差异。手术前后CA199对3年DFS率及5年OS率均没有影响,P0.05,组间比较无统计学差异。手术前后高NLR组对比低NLR组3年DFS率及5年OS率均明显降低,P0.05,组间比较有统计学差异。(二)Ⅲ期患者中,手术前后高CEA组、高CA199组及高NLR组对比低CEA组、低CA199组及低NLR组3年DFS率及5年OS率均明显降低,P0.05,组间比较有统计学差异。四.由CEA、CA199及NLR分层中治疗方式对结直肠癌患者3年DFS率及5年OS率的影响(一)由CEA分层:无论术前CEA的高低,辅助化疗对患者3年DFS率及5年OS率均无影响,P0.05,但术前高CEA的患者进行辅助化疗后3年DFS率有增加的趋势,P=0.058。术后高CEA的患者进行辅助化疗后3年DFS率明显增加,P=0.018,但并不影响患者5年OS率,P0.05,术后低CEA的患者进行辅助化疗后3年DFS率及5年OS率均无明显改善,P0.05。(二)由CA199分层:术前高CA199的患者进行辅助化疗后3年DFS率明显增加,P=0.028,但并不影响患者5年OS率,P0.05,术前低CA199的患者进行辅助化疗后3年DFS率及5年OS率均无明显改善,P0.05。术后高CA199的患者进行辅助化疗后3年DFS率有增加的趋势,P=0.071,但并不影响患者5年OS率,P0.05,术后低CA199的患者进行辅助化疗后3年DFS率及5年OS率均无明显改善,P0.05。(三)由NLR分层:术前高NLR的患者进行辅助化疗后3年DFS率明显增加,P=0.026,但并不影响患者5年OS率,P0.05,术前低NLR的患者进行辅助化疗后3年DFS率及5年OS率均无明显改善,P0.05。术后高NLR的患者进行辅助化疗后3年DFS率及5年OS率明显增加,P值分别为0.032和0.041,术后低NLR的患者进行辅助化疗后3年DFS率及5年OS率均无明显改善,P0.05。五.CEA、CA199及NLR的动态变化对结直肠癌患者3年DFS率及5年OS率的影响50例术前CEA升高者在术后有24例恢复正常,其中26例仍然升高,术后低CEA组对比高CEA组3年DFS率从19.2%上升到41.7%,术后5年OS率从19.2%上升到45.8%,P值分别为0.256和0.052,组间比较无统计学差异。33例术前CA199升高者在术后有10例恢复正常,其中23例仍然升高,术后低CA199组对比高CA199组3年DFS率从26.1%上升到40.0%。,P=0.591,组间比较无统计学差异,而术后CA199的降低对5年OS率没有影响,P0.05,组间比较无统计学差异。70例术前NLR升高者在术后有33例恢复正常,其中37例仍然升高,术后高NLR组对比低NLR组3年DFS率及5年OS率均明显降低,P值均为0.000,组间比较有统计学差异。结论:一、了解CEA的水平有助于对结直肠癌患者进行临床分期以及判断进展情况。二、CEA、CA199及NLR均Ⅱ、Ⅲ期结直肠癌患者的预后标记物,只有NLR是其独立的预后因子。三、CEA及NLR均可预测Ⅱ期和Ⅲ期结直肠癌患者的预后,而CA199可能更好的预测Ⅲ期结直肠癌患者的预后。四、高CEA、高CA199及高NLR的结直肠癌患者可能对辅助化疗更有效。五、对CEA、CA199及NLR进行动态监测可以更好的判断结直肠癌患者的预后。
[Abstract]:Background and purpose: the incidence of colorectal cancer is very high and the mortality is high in the malignant tumors of the digestive system around the world. Early studies confirmed the predictive prognosis of CEA in colorectal cancer, auxiliary staging and the value of.CA199 in the follow-up, although the general clinical application of colorectal cancer was found in colorectal cancer, but it was in colorectal cancer. In recent years, domestic and foreign studies have found that inflammation plays a key role in the occurrence and metastasis of various tumors, and the ratio of neutrophils to lymphocyte (neutrophil-to-lymphocyteratio, NLR) has been proved to be an alternative marker for inflammatory response and has been published in many literature. The report is closely related to the diagnosis, staging and prognosis of colorectal cancer. This study will further explore the relationship between CEA, CA199, NLR and stage II, stage III colorectal cancer patients, in order to provide a more scientific basis and theoretical basis for the accurate diagnosis and treatment of colorectal cancer patients and follow-up monitoring. Method: research object: 200 1 years November 20th -2011 November 20th during the period of radical mastectomy and histopathology proved to be II, stage III of the colorectal cancer patients in a total of 144 cases of retrospective analysis, collection of its complete clinicopathological parameters and follow-up data, and to carry out statistics and analysis. Two. Serum specimens collected in 1. collection of patients within 1 weeks before and after 1 months of postoperative radiotherapy Cancer markers (CEA) and sugar chain antigen 199 (CA199) were used for the anterior tumor markers, and the blood routine markers of neutrophils count (N) and lymphocyte count (L) were collected at the same time. The value of NLR was obtained by the neutrophils count divided by the lymphocyte count. All the test room indexes were not accepted within 1 weeks before and 1 months after the operation. Radiotherapy, without the use of leucocyte drugs or other immunomodulating drugs, all patients had no acute and chronic inflammation, acute injury, blood and immune system related diseases.2. according to our hospital reference range set as follows: CEA5.0ng/ml defined as normal; CA19927.0U/ml defined as normal; the reference range of normal neutrophils count ( 2.0-7.0) * 109/L, the reference range of the normal value of lymphocyte counts was (0.8-4.0) x 109/L. three. Follow up with an electronic medical record or telephone, followed up to November 20, 2016. The definition of the disease free survival (Disease-free survival, DFS) refers to the local recurrence, distant metastasis or distant metastasis from the day of the operation to the disease. The time of death for any reason. The definition of Overall survival (OS) is defined as the time from the day of the operation to any cause of death or the last follow-up date. Four. Statistical methods used the SPSS20.0 software version to make statistical analysis of the data by plotting the characteristics of the subjects (Receiver operati). Ng characteristic, ROC) curves are used to calculate the area under the curve (Area under the curve, AUC) and determine the best truncation value of the NLR by calculating the Jordan index (Youden index, YI). The Kaplan-Meier method was used for the calculation of the rate. The single factor analysis of the patient's survival was examined by Log-rank test. The COX regression model was used to evaluate the independent prognostic factors of the P0.05 in the single factor analysis, and P0.05 was considered to be statistically significant. The result: a.CEA, the relationship between CA199 and NLR and the clinicopathological parameters before the operation CE. A, CA199 and NLR were not related to age, sex, mass size, tumor location, differentiation, pathological type, TNM staging, T staging and N staging, but with the increase of TNM staging, the value of preoperative CEA increased (P=0.085). With the increase of N stage, the value of CEA was also increased. Two The 3 year DFS rate and the effect of 5 year OS rate (one) single factor analysis showed that the level of CEA, CA199 and NLR before and after operation were related factors (P0.05) affecting the 3 year DFS rate and 5 year OS rate of colorectal cancer patients (P0.05). Besides, TNM staging and N staging were also related to the 3 year DFS rate and 5 year OS rate of colorectal cancer patients. The size, tumor location, pathological type and T staging had no effect on the 3 year DFS rate and the 5 year OS rate of colorectal cancer patients (P0.05). The degree of differentiation was associated with the 5 year OS rate of colorectal cancer patients (p=0.015), and had no effect on the 3 year DFS rate (p=0.085). The treatment was related to the 3 year DFS rate of colorectal cancer patients (p=0.019). The 5 year OS rate did not affect (p=0.194). (two) multivariate analysis showed that NLR was an independent prognostic factor for the 3 year DFS rate and 5 year OS rate for colorectal cancer patients. In addition, the degree of differentiation was an independent prognostic factor for 5 year OS rates in colorectal cancer patients. Three. The 3 year DFS and 5 year OS rates of colorectal cancer patients were stratified by TNM stage. In phase II patients, the preoperative CEA level had no effect on the 3 year DFS rate, and there was no statistical difference between the groups. The 5 year OS rate in the high CEA group compared with the low CEA group was significantly lower than that in the low CEA group, and there was a statistical difference between the groups. The 3 year DFS rate and the 5 year OS rate in the high CEA group compared with the low CEA group were significantly reduced, and the P values were 0.001 and 0.002, respectively. The groups were 0.001 and 0.002 respectively. There was no statistical difference. There was no effect on the 3 year DFS rate and the OS rate of 5 years before and after operation, and there was no statistical difference between the groups. The DFS rate and the 5 year OS rate in the high NLR group before and after the operation were significantly lower than those in the low NLR group. (two) the high CEA group, the high CA199 group and the high NLR group before and after the operation were in the patients with stage III (two). Compared with the low CEA group, the 3 year DFS rate and the 5 year OS rate in the low CA199 group and the low NLR group were significantly decreased, and there was a statistical difference between the groups. Four. The effects of the treatment on the 3 year DFS rate and 5 year OS rate of the colorectal cancer patients were influenced by the CEA, CA199 and NLR stratification. There was no effect, P0.05, but the rate of DFS in 3 years after adjuvant chemotherapy for patients with high CEA was increased, and the rate of DFS increased significantly after adjuvant chemotherapy after P=0.058., P=0.018, but did not affect the 5 year OS rate of the patients, P0.05, and the 3 year DFS rate and 5 year OS rate of the patients with low CEA after adjuvant chemotherapy were not significantly improved. Two) CA199 stratification: 3 years after adjuvant chemotherapy, the rate of DFS in patients with high CA199 was significantly increased, P=0.028, but it did not affect the 5 year OS rate of the patients, P0.05. The DFS and 5 year OS rates of the patients with low CA199 before operation were not significantly improved after adjuvant chemotherapy, and the DFS rate of the patients with high CA199 after P0.05. had an increase in the 3 years after adjuvant chemotherapy. 071, but did not affect the patient's 5 year OS rate. P0.05, the DFS rate and OS rate of 5 years after adjuvant chemotherapy for patients with low CA199 after operation were not significantly improved. P0.05. (three) was stratified by NLR: the rate of DFS increased significantly in 3 years after adjuvant chemotherapy for patients with high NLR, P=0.026, but did not respond to the 5 year OS rate, P0.05, and low preoperative patients with adjuvant chemotherapy. There was no significant improvement in the DFS rate and the 5 year OS rate in the last 3 years. The DFS rate and the 5 year OS rate in the patients with high NLR after P0.05. were significantly increased, P values were 0.032 and 0.041 respectively. There was no significant improvement in the DFS rate and 5 year OS rate of the patients with low NLR after adjuvant chemotherapy, and P0.05. five.CEA, and 3 of colorectal cancer patients. The annual DFS rate and the 5 year OS rate influence 50 cases of preoperative CEA elevating in 24 cases restored to normal, of which 26 cases were still elevated, and the 3 year DFS rate in the lower CEA group increased from 19.2% to 41.7%, the OS rate increased from 19.2% to 45.8% after the operation, P value was 0.256 and 0.052 respectively, and there was no statistical difference in the group ratio before the operation in the operation of CA199 elevating in the operation. After that, 10 cases were restored to normal, of which 23 cases were still elevated, and the rate of DFS in the lower CA199 group after the operation was compared with the high CA199 group in 3 years from 26.1% to 40.0%., and there was no statistical difference between the groups, but the decrease of CA199 after the operation had no effect on the 5 year OS rate, and there was no statistical difference between the group and the group of.70 cases before the operation, and 33 cases were restored to normal after the operation. 37 cases still increased. The 3 year DFS rate and 5 year OS rate in the high NLR group were significantly lower than those in the low NLR group, and the P value was 0. There was a statistical difference between the groups. Conclusion: first, the understanding of the level of CEA is helpful to the clinical stages of colorectal cancer patients and the progress of judgement. Two, CEA, CA199 and NLR both, and the prognosis of stage III colorectal cancer patients Only NLR is an independent prognostic factor. Three, CEA and NLR can predict the prognosis of patients with stage II and stage III colorectal cancer, and CA199 may better predict the prognosis of patients with stage III colorectal cancer. Four, high CEA, high CA199 and high NLR colorectal cancer patients may be more effective for adjuvant chemotherapy. Five, CEA, CA199, and NLR are dynamically monitored. To better judge the prognosis of patients with colorectal cancer.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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