術(shù)前血液中未結(jié)合膽紅素水平與食管鱗癌預(yù)后的相關(guān)性分析
發(fā)布時(shí)間：2019-06-14 05:59
【摘要】：研究背景:在世界范圍內(nèi),目前食管癌的發(fā)病率排在第6位,發(fā)展中國家的食管癌患者大約占80%。在中國,食管癌發(fā)病率目前已經(jīng)排在惡性腫瘤中的第3位。食管鱗狀細(xì)胞癌(Esophageal squamous celllcarcinoma,ESCC)是較常見的組織學(xué)類型,在發(fā)展中國家發(fā)病率較高。遠(yuǎn)處轉(zhuǎn)移是導(dǎo)致ESCC患者治療失敗以及死亡的重要原因。因此,研究ESCC遠(yuǎn)處轉(zhuǎn)移的機(jī)制和找出可靠的預(yù)后因子對(duì)于臨床工作非常重要。活性氧是指生物體內(nèi)存在的參與氧代謝過程的含有氧元素的自由基以及非自由基活性分子,其可誘導(dǎo)細(xì)胞內(nèi)的氧化應(yīng)激過程。已有大量的研究表明活性氧和其參與的氧化應(yīng)激過程可以促進(jìn)腫瘤的很多生物學(xué)行為,比如增殖、存活、癌變、輻射抵抗、耐藥、血管生成和轉(zhuǎn)移等。因此,活性氧的抑制劑在腫瘤的化學(xué)預(yù)防中起到至關(guān)重要的作用。間接膽紅素(Unconjugatedbilirubin,UCB)是機(jī)體代謝產(chǎn)生的一種代謝廢物。目前,已經(jīng)有越來越多的研究證明膽紅素在氧化應(yīng)激有關(guān)疾病(比如冠狀動(dòng)脈粥樣硬化、中風(fēng)、冠心病和腫瘤等)中發(fā)揮了重要的保護(hù)性作用。然而,很少有研究涉及膽紅素在腫瘤轉(zhuǎn)移過程中的所發(fā)揮的作用。本研究旨在探討ESCC患者術(shù)前血液中UCB水平與經(jīng)手術(shù)治療的ESCC患者預(yù)后之間的關(guān)系。研究目的:分析術(shù)前血液中未結(jié)合膽紅素水平與ESCC患者預(yù)后的相關(guān)性,探討其對(duì)經(jīng)手術(shù)治療的ESCC患者預(yù)后有無影響,以期找到ESCC新的預(yù)后因子。研究方法:系統(tǒng)地收集在2007年1月-2008年12月兩年間于山東大學(xué)齊魯醫(yī)院胸外科接受食管鱗癌切除術(shù)的336位患者的病例資料,并且收集患者術(shù)前一周檢測的外周血未結(jié)合膽紅素濃度的數(shù)據(jù)。排除不符合研究條件的病例,對(duì)最終納入研究的所有患者進(jìn)行定期隨訪,在術(shù)后2年內(nèi),每3個(gè)月門診隨訪一次,之后改為每6個(gè)月隨訪一次,直至患者出現(xiàn)死亡,隨訪于2013年12月結(jié)束。所有患者術(shù)前均未接受過任何的新輔助治療措施。根據(jù)美國癌癥分期聯(lián)合委員會(huì)制定的分期指南(第7版,2010年)對(duì)患者進(jìn)行TNM分期,然后利用受試者工作特征(ROC)曲線分析獲得最合適的分界點(diǎn),該切點(diǎn)將具有不同遠(yuǎn)處轉(zhuǎn)移或局部復(fù)發(fā)風(fēng)險(xiǎn)的病人進(jìn)行分層�？ǚ綑z驗(yàn)和Kruskal-Wallis檢驗(yàn)進(jìn)行分析UCB絕對(duì)值與臨床病理特點(diǎn)的關(guān)系。利用Kaplan-Meier生存曲線和log-rank檢驗(yàn)對(duì)無病生存期(DFS)和總生存率(OS)進(jìn)行分析比較,并且使用Cox比例風(fēng)險(xiǎn)模型對(duì)最終納入研究的181名患者的特征(如性別、年齡、T分期、N分期、TNM分期、治療形式和間接膽紅素水平)進(jìn)行多因素分析,p0.05時(shí)被認(rèn)為有統(tǒng)計(jì)學(xué)意義。所有統(tǒng)計(jì)分析均使用SPSS21.0統(tǒng)計(jì)軟件。研究結(jié)果:在本研究所納入的181名患者中,共有女性37名(20.4%)和男性144名(79.6%)。診斷為食管癌的中位年齡是60歲(年齡區(qū)間32-84歲)。5年總生存率和5年無病生存率分別是47.0%和52.5%。UCB水平的中位值為8.0μM(四分位間距:5.9-10.3μM)。使用Student's t-檢驗(yàn)方法將男性和女性患者的UCB水平進(jìn)行比較,在男性中UCB平均值為8.05μM,女性中UCB平均值是7.7μM.兩者無統(tǒng)計(jì)學(xué)差異(p=0.524)。由ROC曲線獲得的UCB對(duì)于DFS敏感性和特異性最佳的切點(diǎn)值是6.45μM。單因素分析UCB與DFS的關(guān)系,單因素分析結(jié)果表明,對(duì)于ESCC較高的濃度膽紅素(≥6.45μM)有利于獲得較好的DFS(P0.01)。同時(shí),多因素分析結(jié)果顯示UCB≥6.45μM是有利于DFS的獨(dú)立預(yù)測因子,但對(duì)于OS沒有意義。綜上所述,在ESCC患者中,UCB水平是DFS有利的預(yù)后因子。結(jié)論:UCB是對(duì)ESCC患者DFS有利的獨(dú)立預(yù)后因素。術(shù)前較高的UCB水平(正常生理范圍內(nèi))與較好的DFS具有相關(guān)性。術(shù)前外周血UCB的檢測可以預(yù)測ESCC患者的遠(yuǎn)處轉(zhuǎn)移或局部復(fù)發(fā)情況。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1
本文編號(hào)：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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1
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