本文選題：食管鱗狀細胞癌 + 淋巴—單核細胞比例��； 參考：《華中科技大學(xué)》2016年博士論文

【摘要】：目的：食管鱗狀細胞癌(esophageal squamous cell carcinoma, ESCC)是常見的食管癌組織類型,每年約造成15萬例死亡,在腫瘤相關(guān)死亡中列第4位。目前用于預(yù)測食管鱗癌預(yù)后的臨床指標尚不精確。本研究旨在討論術(shù)前外周血淋巴—單核細胞比例(lymphocyte-monocyte ratio, LMR)、中性—淋巴細胞比例(neutrophil-lymphocyte ratio, NLR)、血小板—淋巴細胞比例(platelet-lymphocyte ratio, PLR)與食管鱗狀細胞癌預(yù)后的相關(guān)性。材料與方法：本研究納入178例接受食管鱗癌根治術(shù)的患者,按患者術(shù)前1周血常規(guī)檢查結(jié)果計算NLR、PLR及LMR,采用中位數(shù)將其分別分成兩組,并用Kaplan-Meier曲線及l(fā)og-rank檢驗分別分析高NLR、PLR、LMR組與低NLR、PLR、LMR組之間總生存時間(overall survival, OS)及無病生存時間(disease-free survival, DFS)的差異。使用Cox回歸模型進行預(yù)后相關(guān)因素與OS、DFS的關(guān)聯(lián)分析。結(jié)果：本研究納入178例食管鱗癌患者,其中女性39例,男性139例,中位年齡是56歲,中位隨訪時間是39月。Kaplan-Meier曲線分析顯示低LMR組總生存時間(P=0.187)和無病生存時間(P=0.400)較高LMR組短,差異無統(tǒng)計學(xué)意義。多因素分析顯示食管鱗癌患者LMR與總生存時間(HR= 0.733,95% CI:0.397-1.353,P=0.321)及無病生存時間(HR= 0.850,95% CI:0.491-1.473, P=0.562)均無顯著相關(guān)。結(jié)論：本研究首次證明LMR不能作為可手術(shù)的食管鱗癌患者獨立的預(yù)后標志。此外,本研究為進一步探索炎癥細胞與免疫細胞在食管鱗癌微環(huán)境中的作用提供支持。目的：食管癌是我國發(fā)病率第4的惡性腫瘤,鱗狀細胞癌占食管癌的90%以上,但目前食管鱗狀細胞癌(esophageal squamous cell carcinoma, ESCC)的五年生存率不足15%。目前用于預(yù)測食管鱗癌預(yù)后的臨床指標尚不精確。本研究旨在討論腫瘤組織浸潤淋巴細胞與食管鱗狀細胞癌預(yù)后的相關(guān)性。材料與方法：本研究納入127例接受食管鱗癌根治術(shù)的患者,由兩位食管癌方向的病理醫(yī)生分別獨立對HE切片中腫瘤上皮浸潤淋巴細胞(intraepithelial tumor-infiltrating lymphocytes, iTILs)及腫瘤基質(zhì)浸潤淋巴細胞上皮浸潤淋巴細胞(stromal tumor-infiltrating lymphocytes, sTILs)比例評分,并采用Kaplan-Meier曲線及l(fā)og-rank檢驗分別分析iTILs與sTILs與總生存時間(overall survival, OS)及無病生存時間(disease-free survival, DFS)的關(guān)系。使用Cox回歸模型進行預(yù)后相關(guān)因素與OS、DFS的關(guān)聯(lián)分析。結(jié)果：參與評分的121例食管鱗癌患者包括25例女性和96例男性患者,中位年齡是58歲,中位隨訪時間是34月。92.6%的腫瘤組織中發(fā)現(xiàn)了不少于10%的基質(zhì)浸潤淋巴細胞(范圍,10%到90%),84.3%的腫瘤組織中發(fā)現(xiàn)了不少于10%的上皮浸潤淋巴細胞(范圍,10%到40%)。Kaplan-Meier曲線分析顯示基質(zhì)浸潤淋巴細胞比例升高,總生存時間(P0.001)及無病生存時間(P=0.025)顯著增加。多因素分析顯示多因素分析顯示基質(zhì)浸潤淋巴細胞與OS (P0.001, HR= 0.968,95% CI 0.955-0.981)及DFS (P= 0.005, HR= 0.982,95% CI 0.970-0.995)相關(guān),差異有統(tǒng)計學(xué)意義。結(jié)論：腫瘤組織HE切片上基質(zhì)浸潤淋巴細胞評分是食管鱗癌根治術(shù)后患者獨立的預(yù)后因素。目的：食管鱗狀細胞癌(esophageal squamous cell carcinoma,ESCC)是常見的食管癌組織類型,每年約造成15萬例死亡,在腫瘤相關(guān)死亡中列第4位。目前用于預(yù)測食管鱗癌預(yù)后的臨床指標尚不精確。本研究旨在討論食管鱗癌組織p14ARF/MDM2/p53信號通路單核苷酸多態(tài)性與預(yù)后的關(guān)系。材料與方法：本研究納入124例接受食管鱗癌根治術(shù)的患者,從患者術(shù)后腫瘤組織的石蠟切片中提取DNA,并采用質(zhì)譜法檢測p14ARF/MDM2/p53信號通路上6個位點的單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)。采用Kaplan-Meier曲線及l(fā)og-rank檢驗分別分析SNP位點基因型與總生存時間(overall survival,OS)及無病生存時間(disease-free survival,DFS)的差異。使用Cox回歸模型進行預(yù)后相關(guān)因素與OS、DFS的關(guān)聯(lián)分析。結(jié)果：本研究納入124例食管鱗癌患者,其中女性28例,男性96例,中位年齡是58歲,中位隨訪時間是37月。Kaplan-Meier曲線分析顯示p144ARF rs3814960位點TC/CC基因型患者較TT基因型患者總生存時間(P=0.001)和無病生存時間(P=0.001)顯著減少。MDM2 rs34886328位點A/- +AA基因型患者較-/-基因型患者總生存時間(P=0.0004)和無病生存時間(P=0.0001)顯著增加。Cox回歸模型多因素分析結(jié)果顯示p14ARF rs3814960位點TC/CC基因型患者總生存時間(]HR=2.765,95% CI: 1.330-5.750,P=0.006,Pc=0.030)和無病生存時間(HR=2.449,95% CI:1.301-4.608,P =0.005,Pc=0.025)較TT基因型患者顯著減少。MDM2 rs34886328位點A/-+AA基因型患者總生存時間(]HR=0.272,95% CI:0.131-0.564,P=4.7×10-4,Pc=0.003)和無病生存時間(]HR=0.217,95% CI:0.109-0.429,P=1.1×10-5,Pc=6.6×10-5)較-/-基因型患者顯著增加結(jié)論：本研究首次證明可手術(shù)的食管鱗癌患者腫瘤組織中p14ARF rs3814960和MDM2rs34886328位點多態(tài)性與預(yù)后相關(guān),在以后的研究中經(jīng)大樣本人群驗證可作為食管鱗狀細胞癌獨立的預(yù)后標志。目的：我國90%以上的食管癌屬于食管鱗癌,每年有25萬新發(fā)病例,約造成15萬例死亡,在腫瘤相關(guān)死亡中列第4位。目前用于預(yù)測食管鱗癌預(yù)后的臨床指標尚不精確。HPV在宮頸癌發(fā)生發(fā)展中起重要作用,也是口咽癌、肛管癌、宮頸癌獨立的預(yù)后因素。本研究旨在探索食管鱗癌患者腫瘤組織HPV感染亞型與預(yù)后的相關(guān)性。材料與方法：本研究納入135例接受食管鱗癌根治術(shù)的患者,提取術(shù)后食管鱗癌組織石蠟切片中的DNA,采用基質(zhì)輔助激光解析／電離飛行時間質(zhì)譜法(MALDI-TOF MS)及PCR法檢測DNA樣品中的14種HPV亞型(HPV16、18、31、33、35、39、45、51、52、56、58、59、66、68),并使用SPSS 16.0軟件進行統(tǒng)計學(xué)分析。結(jié)果：本研究納入135例食管鱗癌患者,其中26例為女性,109例為男性患者,中位年齡是58歲。MALDI-TOF MS法檢測發(fā)現(xiàn)僅有1例患者感染了HPV16,占患者總數(shù)的0.74%。其余13種HPV在135例食管鱗癌患者腫瘤組織中均未檢出。PCR法檢測135例食管鱗癌患者腫瘤組織DNA中,僅有1例存在HPV感染。結(jié)論：由于本研究樣本量小,且食管鱗癌組織中HPV感染率較低,因此我們尚無法證實腫瘤組織HPV感染與食管鱗癌預(yù)后的關(guān)系。此外,由于食管癌發(fā)病率和HPV感染率具有較大地區(qū)性差異,我們推測在不同地區(qū)HPV感染在食管鱗癌致病過程中的作用可能并不相同,HPV可能不是我國中部地區(qū)食管鱗狀細胞癌患者的重要致病因素。
[Abstract]:Objective: esophageal squamous cell carcinoma (ESCC) is a common type of esophageal carcinoma, which causes 150 thousand deaths each year and fourth in tumor related deaths. The current clinical indicators for predicting the prognosis of esophageal squamous cell carcinoma are not yet accurate. Lymphocyte-monocyte ratio, LMR), the relationship between the neutral lymphocyte proportion (neutrophil-lymphocyte ratio, NLR), the proportion of platelet - lymphocyte (platelet-lymphocyte ratio, PLR) and the prognosis of esophageal squamous cell carcinoma. Materials and methods: This study was included in 178 patients undergoing radical resection of esophageal squamous cell carcinoma and 1 weeks before the operation. The results of routine examination were calculated NLR, PLR and LMR, which were divided into two groups by the median, and the difference between the high NLR, PLR, LMR group and low NLR, PLR, LMR group and disease free survival time between the high NLR, LMR group and the LMR group were analyzed respectively by the Kaplan-Meier curve and log-rank test. Results: the correlation analysis of prognostic factors and OS, DFS. Results: 178 cases of esophageal squamous cell carcinoma were included in this study, of which 39 cases were female, 139 cases were male, the median age was 56 years, and the median follow-up time was 39 months.Kaplan-Meier curve analysis showed that the total survival time of the low LMR group (P=0.187) and the higher LMR group with the disease free survival time (P=0.400) were shorter, and the difference was not statistically significant Multivariate analysis showed no significant correlation between LMR and total survival time (HR= 0.733,95% CI:0.397-1.353, P=0.321) and disease-free survival time (HR= 0.850,95% CI:0.491-1.473, P=0.562) in esophageal squamous cell carcinoma. Conclusion: This study is the first to prove that LMR can not be used as an independent prognostic marker in operable esophageal squamous cell carcinoma. In addition, this study To further explore the role of inflammatory cells and immune cells in the microenvironment of squamous cell carcinoma of the esophagus. Objective: esophageal cancer is a malignant tumor of fourth in China. Squamous cell carcinoma accounts for more than 90% of the cancer of the esophagus, but the five year survival rate of esophageal squamous cell carcinoma (ESCC) is less than 15%. at present. The clinical indicators for predicting the prognosis of esophageal squamous cell carcinoma are not accurate. The purpose of this study was to discuss the correlation between tumor tissue infiltrating lymphocytes and the prognosis of squamous cell carcinoma of the esophagus. Materials and methods: This study included 127 patients undergoing radical resection of esophageal squamous cell carcinoma, and two pathologists in the direction of esophageal cancer were independent of the tumor in the HE section. The proportion of intraepithelial tumor-infiltrating lymphocytes (iTILs) and tumor matrix infiltrating lymphocyte epithelial infiltrating lymphocytes (stromal tumor-infiltrating lymphocytes, sTILs) was scored. The Kaplan-Meier curve and log-rank test were used to analyze iTILs and sTILs and total survival time. OS) and disease-free survival time (disease-free survival, DFS). A Cox regression model was used to analyze the correlation between prognostic factors and OS, DFS. Results: 121 cases of esophageal squamous cell carcinoma included 25 women and 96 male patients with a median age of 58 years, and a median follow-up time of 34 month.92.6% in tumor tissues. No less than 10% of the stromal infiltrating lymphocytes (range, 10% to 90%), 84.3% of the tumor tissues found not less than 10% of the epithelial infiltrating lymphocytes (range, 10% to 40%).Kaplan-Meier curve analysis showed that the proportion of stromal infiltrating lymphocytes increased, the total survival time (P0.001) and the disease-free survival time (P=0.025) increased significantly. Multiple factor analysis showed that the number of infiltrating lymphocytes increased significantly. The multifactor analysis showed that the stromal infiltrating lymphocytes were related to OS (P0.001, HR= 0.968,95% CI 0.955-0.981) and DFS (P= 0.005, HR= 0.982,95% CI 0.970-0.995). The difference was statistically significant. Conclusion: the matrix infiltrating lymphocyte score on the tumor tissue section is an independent prognostic factor after radical resection of the carcinoma of food. Esophageal squamous cell carcinoma (ESCC) is a common type of esophageal carcinoma, which causes 150 thousand deaths per year and fourth in tumor related deaths. The clinical indicators used to predict the prognosis of esophageal squamous cell carcinoma are not accurate. The purpose of this study is to discuss the single nucleus of p14ARF/MDM2/p53 signaling pathway in esophageal squamous cell carcinoma. The relationship between glucoside polymorphism and prognosis. Materials and methods: This study included 124 patients undergoing radical resection of esophageal squamous cell carcinoma, extracted DNA from the paraffin section of the tumor tissue after operation, and detected the single nucleotide polymorphisms (single nucleotide polymorphism, SNP) of the 6 loci on the p14ARF/MDM2/p53 signaling pathway by mass spectrometry. The use of Kap Lan-Meier curve and log-rank test were used to analyze the difference between the genotype of SNP loci and the total survival time (overall survival, OS) and the disease free survival time (disease-free survival, DFS). A Cox regression model was used to analyze the correlation between the prognostic factors and OS and DFS. Results: 124 cases of esophageal squamous cell carcinoma were included in this study, of which 28 cases, male, male, male, male and female. The median age was 58 years, and the median follow-up time was 37 months.Kaplan-Meier curve analysis showed that the total survival time (P=0.001) and the disease free survival time (P=0.001) of the p144ARF rs3814960 locus TC/CC genotype patients significantly reduced the total survival time of the patients with the A/- + AA genotype of.MDM2 rs34886328 loci (P=) (P=) (P=). 0.0004) and a significant increase in the.Cox regression model with the disease free survival time (P=0.0001). The results of the.Cox regression model showed that the total survival time (]HR=2.765,95% CI: 1.330-5.750, P=0.006, Pc=0.030) and the disease-free survival time of the p14ARF rs3814960 locus were significantly lower than those of the genotype patients. The total survival time (]HR=0.272,95% CI:0.131-0.564, P=4.7 x 10-4, Pc=0.003) and disease-free survival time (]HR=0.217,95% CI:0.109-0.429, P=1.1 x 10-5, Pc=6.6 x 10-5) in patients with the MDM2 rs34886328 locus A/-+AA genotype were significantly higher than those in the type / - genotype patients. This study was the first to prove that the tumor tissue of the patients with esophageal squamous cell carcinoma could be operated for the first time. The polymorphism of rs3814960 and MDM2rs34886328 loci is associated with the prognosis. In future studies, a large sample population can be used as an independent prognostic marker for esophageal squamous cell carcinoma. Objective: more than 90% of the esophageal cancer in China belongs to esophageal squamous cell carcinoma, with more than 25 million new cases each year, resulting in about 150 thousand deaths, and fourth in tumor related deaths. The clinical indicators used to predict the prognosis of squamous cell carcinoma of the esophagus are still inaccurate and.HPV plays an important role in the development of cervical cancer. It is also an independent prognostic factor for oropharyngeal, anal and cervical cancer. The purpose of this study was to explore the correlation between the subtype of HPV infection and the prognosis of the tumor tissues of the patients with esophageal squamous cell carcinoma. Materials and methods: the study was included in 135 cases. DNA in paraffin section of esophageal squamous cell carcinoma was extracted after radical resection of esophageal squamous cell carcinoma. 14 HPV subtypes (HPV16,18,31,33,35,39,45,51,52,56,58,59,66,68) in DNA samples were detected by matrix assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF MS) and PCR method, and SPSS 16 software was used for statistical analysis. Fruit: 135 cases of esophageal squamous cell carcinoma were included in this study, of which 26 were female and 109 were male. The median age was 58 year old.MALDI-TOF MS detection. Only 1 patients were infected with HPV16, and the other 13 HPV in the total number of 0.74%. were not detected by.PCR in 135 cases of esophageal squamous cell carcinoma in 135 cases of esophageal squamous cell carcinoma. In the tumor tissue DNA, only 1 cases have HPV infection. Conclusion: because of the small sample size and low HPV infection rate in the squamous cell carcinoma of the esophagus, we can not confirm the relationship between the HPV infection and the prognosis of the squamous cell carcinoma of the esophagus. In addition, we speculate that the incidence of esophageal cancer and the rate of HPV infection have great regional differences. The role of HPV infection in the pathogenesis of esophageal squamous cell carcinoma may not be the same. HPV may not be an important pathogenic factor for patients with squamous cell carcinoma of the esophagus in Central China.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R735.1

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