本文選題：CEA + CA199　； 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景與目的:在全球范圍內(nèi)消化系統(tǒng)的惡性腫瘤中,結(jié)直腸癌的發(fā)病率極高,死亡率也居高不下。早期的研究確認(rèn)了 CEA在結(jié)直腸癌中預(yù)測預(yù)后、輔助分期及隨訪中的價值。CA199固然在結(jié)直腸癌中得到了普遍的臨床應(yīng)用,但其在結(jié)直腸癌中的輔助分期及展望預(yù)后等方面的價值存在分歧。近年來,國內(nèi)外研究發(fā)現(xiàn)炎癥在多種腫瘤的發(fā)生及轉(zhuǎn)移中發(fā)揮關(guān)鍵作用,而中性粒細(xì)胞與淋巴細(xì)胞比值(neutrophil-to-lymphocyteratio,NLR)被證實可以作為炎癥反應(yīng)的替代標(biāo)志物,已被多篇文獻(xiàn)報道與結(jié)直腸癌的診斷、分期及預(yù)后密切相關(guān)。本研究將對CEA、CA199及NLR和Ⅱ、Ⅲ期結(jié)直腸癌患者的關(guān)系進(jìn)行進(jìn)一步探討,以期為結(jié)直腸癌患者的精準(zhǔn)診治及隨訪監(jiān)測提供更為科學(xué)的臨床指導(dǎo)依據(jù)和理論基礎(chǔ)。方法:一.研究對象:對我院2001年11月20日-2011年11月20日期間行根治術(shù)并經(jīng)組織病理學(xué)證明為Ⅱ、Ⅲ期的結(jié)直腸癌患者共144例進(jìn)行回顧性分析,收集其完整的臨床病理學(xué)參數(shù)及隨訪資料,并進(jìn)行統(tǒng)計和分析。二.血清標(biāo)本收集1.收集患者術(shù)前1周內(nèi)及術(shù)后1個月內(nèi)化放療前的腫瘤標(biāo)記物指標(biāo)癌胚抗原(CEA)和糖鏈抗原199(CA199),同時收集血常規(guī)指標(biāo)中性粒細(xì)胞計數(shù)(N)及淋巴細(xì)胞計數(shù)(L),NLR的值通過中性粒細(xì)胞計數(shù)除以淋巴細(xì)胞計數(shù)獲得。所獲取的全部實驗室指標(biāo)均在術(shù)前1周內(nèi)及術(shù)后1個月內(nèi)未接受過化放療、未使用升白細(xì)胞藥物或其他免疫藥物下測得,所有患者均無急慢性炎癥、急性損傷、血液及免疫系統(tǒng)相關(guān)的疾病。2.根據(jù)我院的參考值范圍設(shè)定如下:CEA5.0ng/ml定義為正常;CA19927.0U/ml定義為正常;中性粒細(xì)胞計數(shù)正常值的參考范圍為(2.0-7.0)× 109/L、淋巴細(xì)胞計數(shù)正常值的參考范圍為(0.8-4.0)× 109/L。三.隨訪采取電子病歷或電話的方式對每個患者隨訪,隨訪時間截止到2016年11月20日。無病生存期(Disease-free survival,DFS)的定義是指從手術(shù)之日起至疾病局部復(fù)發(fā)、遠(yuǎn)處轉(zhuǎn)移或由于任何原因?qū)е滤劳龅臅r間�？偵嫫�(Overall survival,OS)的定義是指從手術(shù)之日起至任何原因引起的死亡或最后一次隨訪日期的時間。四.統(tǒng)計學(xué)方法使用SPSS20.0軟件版本對數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)分析,通過繪制受試者工作特征(Receiver operating characteristic,ROC)曲線來計算曲線下面積(Area under the curve,AUC),并通過計算約登指數(shù)(Youden index,YI)來確定NLR的最佳截斷值。使用Pearson x 2檢驗或Fishier精確概率法分析CEA、CA199及NLR與各臨床病理學(xué)參數(shù)之間的相關(guān)性。生存曲線的繪制和生存率的計算采取Kaplan-Meier方法,患者生存的單因素分析采取Log-rank檢驗,采用COX回歸模型對單因素分析中P0.05者進(jìn)行多因素分析評估獨立預(yù)后因子,以P0.05被認(rèn)為差異有統(tǒng)計學(xué)意義。結(jié)果:一.CEA、CA199及NLR與臨床病理學(xué)參數(shù)之間的關(guān)系術(shù)前CEA、CA199及NLR與年齡、性別、腫塊大小、腫瘤位置、分化程度、病理類型、TNM分期、T分期及N分期均無相關(guān)性,P0.05。但隨著TNM分期的增加,術(shù)前CEA的值有增加的趨勢(P=0.085),隨著N分期的增加,術(shù)前CEA的值也有增加的趨勢(P=0.090)。二.CEA、CA199及NLR對結(jié)直腸癌患者3年DFS率及5年OS率的影響(一)單因素分析顯示,手術(shù)前后CEA、CA199及NLR的水平均是影響結(jié)直腸癌患者3年DFS率及5年OS率的相關(guān)因素(p0.05),此外TNM分期及N分期也是影響結(jié)直腸癌患者3年DFS率及5年OS率的相關(guān)因素(p0.05)。而年齡、性別、腫塊大小、腫瘤位置、病理類型及T分期對結(jié)直腸癌患者3年DFS率及5年OS率均沒有影響(p0.05)。分化程度是影響結(jié)直腸癌患者5年OS率的相關(guān)因素(p=0.015),對3年DFS率沒有影響(p=0.085)。治療方式是影響結(jié)直腸癌患者3年DFS率的相關(guān)因素(p=0.019),對5年OS率沒有影響(p=0.194)。(二)多因素分析顯示,手術(shù)前后NLR是結(jié)直腸癌患者3年DFS率及5年OS率的獨立預(yù)后因素。此外,分化程度也是結(jié)直腸癌患者5年OS率的獨立預(yù)后因素。三.由TNM分期分層中CEA、CA199及NLR對結(jié)直腸癌患者3年DFS率及5年OS率的影響(一)Ⅱ期患者中,術(shù)前CEA高低對3年DFS率沒有影響,P0.05,組間比較無統(tǒng)計學(xué)差異;術(shù)前高CEA組對比低CEA組5年OS率明顯降低,P=0.024,組間比較有統(tǒng)計學(xué)差異。術(shù)后高CEA組對比低CEA組3年DFS率及5年OS率均明顯降低,P值分別為0.001和0.002,組間比較有統(tǒng)計學(xué)差異。手術(shù)前后CA199對3年DFS率及5年OS率均沒有影響,P0.05,組間比較無統(tǒng)計學(xué)差異。手術(shù)前后高NLR組對比低NLR組3年DFS率及5年OS率均明顯降低,P0.05,組間比較有統(tǒng)計學(xué)差異。(二)Ⅲ期患者中,手術(shù)前后高CEA組、高CA199組及高NLR組對比低CEA組、低CA199組及低NLR組3年DFS率及5年OS率均明顯降低,P0.05,組間比較有統(tǒng)計學(xué)差異。四.由CEA、CA199及NLR分層中治療方式對結(jié)直腸癌患者3年DFS率及5年OS率的影響(一)由CEA分層:無論術(shù)前CEA的高低,輔助化療對患者3年DFS率及5年OS率均無影響,P0.05,但術(shù)前高CEA的患者進(jìn)行輔助化療后3年DFS率有增加的趨勢,P=0.058。術(shù)后高CEA的患者進(jìn)行輔助化療后3年DFS率明顯增加,P=0.018,但并不影響患者5年OS率,P0.05,術(shù)后低CEA的患者進(jìn)行輔助化療后3年DFS率及5年OS率均無明顯改善,P0.05。(二)由CA199分層:術(shù)前高CA199的患者進(jìn)行輔助化療后3年DFS率明顯增加,P=0.028,但并不影響患者5年OS率,P0.05,術(shù)前低CA199的患者進(jìn)行輔助化療后3年DFS率及5年OS率均無明顯改善,P0.05。術(shù)后高CA199的患者進(jìn)行輔助化療后3年DFS率有增加的趨勢,P=0.071,但并不影響患者5年OS率,P0.05,術(shù)后低CA199的患者進(jìn)行輔助化療后3年DFS率及5年OS率均無明顯改善,P0.05。(三)由NLR分層:術(shù)前高NLR的患者進(jìn)行輔助化療后3年DFS率明顯增加,P=0.026,但并不影響患者5年OS率,P0.05,術(shù)前低NLR的患者進(jìn)行輔助化療后3年DFS率及5年OS率均無明顯改善,P0.05。術(shù)后高NLR的患者進(jìn)行輔助化療后3年DFS率及5年OS率明顯增加,P值分別為0.032和0.041,術(shù)后低NLR的患者進(jìn)行輔助化療后3年DFS率及5年OS率均無明顯改善,P0.05。五.CEA、CA199及NLR的動態(tài)變化對結(jié)直腸癌患者3年DFS率及5年OS率的影響50例術(shù)前CEA升高者在術(shù)后有24例恢復(fù)正常,其中26例仍然升高,術(shù)后低CEA組對比高CEA組3年DFS率從19.2%上升到41.7%,術(shù)后5年OS率從19.2%上升到45.8%,P值分別為0.256和0.052,組間比較無統(tǒng)計學(xué)差異。33例術(shù)前CA199升高者在術(shù)后有10例恢復(fù)正常,其中23例仍然升高,術(shù)后低CA199組對比高CA199組3年DFS率從26.1%上升到40.0%。,P=0.591,組間比較無統(tǒng)計學(xué)差異,而術(shù)后CA199的降低對5年OS率沒有影響,P0.05,組間比較無統(tǒng)計學(xué)差異。70例術(shù)前NLR升高者在術(shù)后有33例恢復(fù)正常,其中37例仍然升高,術(shù)后高NLR組對比低NLR組3年DFS率及5年OS率均明顯降低,P值均為0.000,組間比較有統(tǒng)計學(xué)差異。結(jié)論:一、了解CEA的水平有助于對結(jié)直腸癌患者進(jìn)行臨床分期以及判斷進(jìn)展情況。二、CEA、CA199及NLR均Ⅱ、Ⅲ期結(jié)直腸癌患者的預(yù)后標(biāo)記物,只有NLR是其獨立的預(yù)后因子。三、CEA及NLR均可預(yù)測Ⅱ期和Ⅲ期結(jié)直腸癌患者的預(yù)后,而CA199可能更好的預(yù)測Ⅲ期結(jié)直腸癌患者的預(yù)后。四、高CEA、高CA199及高NLR的結(jié)直腸癌患者可能對輔助化療更有效。五、對CEA、CA199及NLR進(jìn)行動態(tài)監(jiān)測可以更好的判斷結(jié)直腸癌患者的預(yù)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.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34

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