术前血液中未结合胆红素水平与食管鳞癌预后的相关性分析
发布时间：2019-06-14 05:59
【摘要】：研究背景:在世界范围内,目前食管癌的发病率排在第6位,发展中国家的食管癌患者大约占80%。在中国,食管癌发病率目前已经排在恶性肿瘤中的第3位。食管鳞状细胞癌(Esophageal squamous celllcarcinoma,ESCC)是较常见的组织学类型,在发展中国家发病率较高。远处转移是导致ESCC患者治疗失败以及死亡的重要原因。因此,研究ESCC远处转移的机制和找出可靠的预后因子对于临床工作非常重要。活性氧是指生物体内存在的参与氧代谢过程的含有氧元素的自由基以及非自由基活性分子,其可诱导细胞内的氧化应激过程。已有大量的研究表明活性氧和其参与的氧化应激过程可以促进肿瘤的很多生物学行为,比如增殖、存活、癌变、辐射抵抗、耐药、血管生成和转移等。因此,活性氧的抑制剂在肿瘤的化学预防中起到至关重要的作用。间接胆红素(Unconjugatedbilirubin,UCB)是机体代谢产生的一种代谢废物。目前,已经有越来越多的研究证明胆红素在氧化应激有关疾病(比如冠状动脉粥样硬化、中风、冠心病和肿瘤等)中发挥了重要的保护性作用。然而,很少有研究涉及胆红素在肿瘤转移过程中的所发挥的作用。本研究旨在探讨ESCC患者术前血液中UCB水平与经手术治疗的ESCC患者预后之间的关系。研究目的:分析术前血液中未结合胆红素水平与ESCC患者预后的相关性,探讨其对经手术治疗的ESCC患者预后有无影响,以期找到ESCC新的预后因子。研究方法:系统地收集在2007年1月-2008年12月两年间于山东大学齐鲁医院胸外科接受食管鳞癌切除术的336位患者的病例资料,并且收集患者术前一周检测的外周血未结合胆红素浓度的数据。排除不符合研究条件的病例,对最终纳入研究的所有患者进行定期随访,在术后2年内,每3个月门诊随访一次,之后改为每6个月随访一次,直至患者出现死亡,随访于2013年12月结束。所有患者术前均未接受过任何的新辅助治疗措施。根据美国癌症分期联合委员会制定的分期指南(第7版,2010年)对患者进行TNM分期,然后利用受试者工作特征(ROC)曲线分析获得最合适的分界点,该切点将具有不同远处转移或局部复发风险的病人进行分层。卡方检验和Kruskal-Wallis检验进行分析UCB绝对值与临床病理特点的关系。利用Kaplan-Meier生存曲线和log-rank检验对无病生存期(DFS)和总生存率(OS)进行分析比较,并且使用Cox比例风险模型对最终纳入研究的181名患者的特征(如性别、年龄、T分期、N分期、TNM分期、治疗形式和间接胆红素水平)进行多因素分析,p0.05时被认为有统计学意义。所有统计分析均使用SPSS21.0统计软件。研究结果:在本研究所纳入的181名患者中,共有女性37名(20.4%)和男性144名(79.6%)。诊断为食管癌的中位年龄是60岁(年龄区间32-84岁)。5年总生存率和5年无病生存率分别是47.0%和52.5%。UCB水平的中位值为8.0μM(四分位间距:5.9-10.3μM)。使用Student's t-检验方法将男性和女性患者的UCB水平进行比较,在男性中UCB平均值为8.05μM,女性中UCB平均值是7.7μM.两者无统计学差异(p=0.524)。由ROC曲线获得的UCB对于DFS敏感性和特异性最佳的切点值是6.45μM。单因素分析UCB与DFS的关系,单因素分析结果表明,对于ESCC较高的浓度胆红素(≥6.45μM)有利于获得较好的DFS(P0.01)。同时,多因素分析结果显示UCB≥6.45μM是有利于DFS的独立预测因子,但对于OS没有意义。综上所述,在ESCC患者中,UCB水平是DFS有利的预后因子。结论:UCB是对ESCC患者DFS有利的独立预后因素。术前较高的UCB水平(正常生理范围内)与较好的DFS具有相关性。术前外周血UCB的检测可以预测ESCC患者的远处转移或局部复发情况。
[Abstract]:Background: In the world, the incidence of esophageal cancer in the world is at the 6th place, and the patients with esophageal cancer in developing countries account for about 80%. In China, the incidence of esophageal cancer is now the third in the malignant tumor. Esophageal squamous cell carcinoma (ESCC) is a more common histological type, and the incidence of esophageal squamous cell carcinoma (ESCC) is higher in developing countries. Distant metastasis is an important cause of failure and death in patients with ESCC. Therefore, it is very important to study the mechanism of distant metastasis of ESCC and to find a reliable prognostic factor. Active oxygen is a free radical containing oxygen and a non-free radical active molecule that is present in the organism that is involved in the oxygen metabolism process, which can induce oxidative stress in the cell. A large number of studies have shown that the oxidative stress processes involved in active oxygen and their participation can promote many of the biological behavior of the tumor, such as proliferation, survival, canceration, radiation resistance, drug resistance, angiogenesis and metastasis. Therefore, the inhibitor of active oxygen plays an important role in the chemical prevention of the tumor. Uncontrolled Bilirubin (UCB) is a metabolic waste produced by the body metabolism. At present, more and more studies have shown that bilirubin plays an important protective role in oxidative stress-related diseases, such as coronary atherosclerosis, stroke, coronary heart disease, and tumors. However, there are few studies involved in the role of bilirubin in the process of tumor metastasis. The purpose of this study was to investigate the relationship between the level of UCB in preoperative blood of patients with ESCC and the prognosis of patients with ESCC treated by surgery. Objective: To study the relationship between the unconjugated bilirubin level and the prognosis of the patients with ESCC in the pre-operative blood, and to explore the effect of the prognosis of the patients with ESCC treated by the operation with a view to finding a new prognostic factor for ESCC. Methods: The data of 336 patients who received esophageal squamous cell carcinoma in the thoracic surgery of Qilu Hospital of Shandong University from January 2007 to December 2008 were systematically collected, and the data of the unconjugated bilirubin concentration in the peripheral blood detected by the patients before and after the operation were collected. Patients who did not meet the study conditions were followed by a regular follow-up of all patients who were eventually included in the study, followed by a follow-up every 3 months after the procedure, followed by a follow-up every 6 months until the patient died and the follow-up ended in December 2013. None of the patients had received any new adjuvant treatment prior to operation. The TNM staging was performed on the patient in accordance with the Staging Guide (version 7,2010) developed by the Joint Commission on Cancer in the United States, and then the most appropriate cut-off point was obtained using the subject's work characteristics (ROC) curve analysis, The point of tangency will be stratified by patients with different distant metastases or local recurrence risks. The relationship between the absolute value of the UCB and the clinical pathology was analyzed by the Chi-square test and the Kruskal-Wallis test. The disease-free survival (DFS) and overall survival (OS) were analyzed and compared using the Kaplan-Meier survival curve and the log-rank test, and the characteristics of 181 patients (e.g., gender, age, T staging, N staging, TNM staging, Multi-factor analysis was performed on the level of treatment and indirect bilirubin, and was considered to be statistically significant at p0.05. The SPSS21.0 statistical software was used for all statistical analyses. Results: Of the 181 patients included in this study, there were 37 female (20.4%) and 144 (79.6%) males. The median age for the diagnosis of esophageal cancer was 60 years (age range 32-84 years). The 5-year overall survival rate and the 5-year disease-free survival rate were 47.0% and 52.5%, respectively. The median value of the UCB level was 8.0. m The UCB level of the male and female patients was compared using the Student's t-test method, with an average of 8.05. m u.M in the male and 7.7. m u.M in the female, with no statistical difference (p = 0.524). The value of UCB obtained by the ROC curve is 6.45. m u.M for DFS sensitivity and specificity, and the single factor analysis of the relationship between UCB and DFS. The results of single factor analysis show that higher concentration bilirubin (p6.45. mu.M) for ESCC is favorable for obtaining better DFS (P0.01). At the same time, the multi-factor analysis results show that UCB-6.45. m is an independent predictor of DFS, but there is no significance for OS. In summary, in patients with ESCC, the UCB level is a favorable prognostic factor for DFS. Conclusion: UCB is an independent prognostic factor for DFS in ESCC patients. A higher preoperative UCB level (in normal physiological range) was associated with better DFS. The detection of pre-operative peripheral blood UCB can predict distant metastasis or local recurrence of ESCC patients.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1
本文编号：2499166
[Abstract]:Background: In the world, the incidence of esophageal cancer in the world is at the 6th place, and the patients with esophageal cancer in developing countries account for about 80%. In China, the incidence of esophageal cancer is now the third in the malignant tumor. Esophageal squamous cell carcinoma (ESCC) is a more common histological type, and the incidence of esophageal squamous cell carcinoma (ESCC) is higher in developing countries. Distant metastasis is an important cause of failure and death in patients with ESCC. Therefore, it is very important to study the mechanism of distant metastasis of ESCC and to find a reliable prognostic factor. Active oxygen is a free radical containing oxygen and a non-free radical active molecule that is present in the organism that is involved in the oxygen metabolism process, which can induce oxidative stress in the cell. A large number of studies have shown that the oxidative stress processes involved in active oxygen and their participation can promote many of the biological behavior of the tumor, such as proliferation, survival, canceration, radiation resistance, drug resistance, angiogenesis and metastasis. Therefore, the inhibitor of active oxygen plays an important role in the chemical prevention of the tumor. Uncontrolled Bilirubin (UCB) is a metabolic waste produced by the body metabolism. At present, more and more studies have shown that bilirubin plays an important protective role in oxidative stress-related diseases, such as coronary atherosclerosis, stroke, coronary heart disease, and tumors. However, there are few studies involved in the role of bilirubin in the process of tumor metastasis. The purpose of this study was to investigate the relationship between the level of UCB in preoperative blood of patients with ESCC and the prognosis of patients with ESCC treated by surgery. Objective: To study the relationship between the unconjugated bilirubin level and the prognosis of the patients with ESCC in the pre-operative blood, and to explore the effect of the prognosis of the patients with ESCC treated by the operation with a view to finding a new prognostic factor for ESCC. Methods: The data of 336 patients who received esophageal squamous cell carcinoma in the thoracic surgery of Qilu Hospital of Shandong University from January 2007 to December 2008 were systematically collected, and the data of the unconjugated bilirubin concentration in the peripheral blood detected by the patients before and after the operation were collected. Patients who did not meet the study conditions were followed by a regular follow-up of all patients who were eventually included in the study, followed by a follow-up every 3 months after the procedure, followed by a follow-up every 6 months until the patient died and the follow-up ended in December 2013. None of the patients had received any new adjuvant treatment prior to operation. The TNM staging was performed on the patient in accordance with the Staging Guide (version 7,2010) developed by the Joint Commission on Cancer in the United States, and then the most appropriate cut-off point was obtained using the subject's work characteristics (ROC) curve analysis, The point of tangency will be stratified by patients with different distant metastases or local recurrence risks. The relationship between the absolute value of the UCB and the clinical pathology was analyzed by the Chi-square test and the Kruskal-Wallis test. The disease-free survival (DFS) and overall survival (OS) were analyzed and compared using the Kaplan-Meier survival curve and the log-rank test, and the characteristics of 181 patients (e.g., gender, age, T staging, N staging, TNM staging, Multi-factor analysis was performed on the level of treatment and indirect bilirubin, and was considered to be statistically significant at p0.05. The SPSS21.0 statistical software was used for all statistical analyses. Results: Of the 181 patients included in this study, there were 37 female (20.4%) and 144 (79.6%) males. The median age for the diagnosis of esophageal cancer was 60 years (age range 32-84 years). The 5-year overall survival rate and the 5-year disease-free survival rate were 47.0% and 52.5%, respectively. The median value of the UCB level was 8.0. m The UCB level of the male and female patients was compared using the Student's t-test method, with an average of 8.05. m u.M in the male and 7.7. m u.M in the female, with no statistical difference (p = 0.524). The value of UCB obtained by the ROC curve is 6.45. m u.M for DFS sensitivity and specificity, and the single factor analysis of the relationship between UCB and DFS. The results of single factor analysis show that higher concentration bilirubin (p6.45. mu.M) for ESCC is favorable for obtaining better DFS (P0.01). At the same time, the multi-factor analysis results show that UCB-6.45. m is an independent predictor of DFS, but there is no significance for OS. In summary, in patients with ESCC, the UCB level is a favorable prognostic factor for DFS. Conclusion: UCB is an independent prognostic factor for DFS in ESCC patients. A higher preoperative UCB level (in normal physiological range) was associated with better DFS. The detection of pre-operative peripheral blood UCB can predict distant metastasis or local recurrence of ESCC patients.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1
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