本文選題：IRF4/MUM1 + 彌漫大B細(xì)胞淋巴瘤�。� 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本研究的目的是引入半?yún)?shù)時(shí)依AUC方法(semi-parametric time-dependent AUC method)來評(píng)估IRF4/MUM1的表達(dá)對(duì)彌漫大B細(xì)胞淋巴瘤(DLBCL)患者的預(yù)后價(jià)值。本研究分為兩部分,第一部分Meta分析,全面和定量的研究了IRF4/MUM1表達(dá)與DLBCL患者預(yù)后之間的關(guān)系。另一部分是方法應(yīng)用,使用半?yún)?shù)時(shí)依AUC方法來評(píng)估,添加一個(gè)腫瘤標(biāo)志物IRF4/MUM1后是否會(huì)改善國際預(yù)后指數(shù)(IPI)對(duì)DLBCL患者預(yù)后的預(yù)測(cè)準(zhǔn)確度。方法:檢索Pubmed,萬方和CNKI數(shù)據(jù)庫從建庫到2016年12月已發(fā)表的關(guān)于IRF4/MUM1與彌漫性大B細(xì)胞淋巴瘤的預(yù)后有關(guān)的所有中英文文獻(xiàn),過程中由兩名評(píng)價(jià)者獨(dú)立完成文獻(xiàn)閱讀。提取IRF4/MUM1正常組和升高組總體生存率(OS)的HR及HR95%CI,并采用固定效應(yīng)模型對(duì)其進(jìn)行合并,考慮到多種因素影響進(jìn)行亞組分析,采用敏感性分析估計(jì)合并風(fēng)險(xiǎn)比的變化情況。在本文中,我們采用半?yún)?shù)時(shí)依AUC方法構(gòu)建關(guān)于時(shí)間t的AUC(t)函數(shù),使用靈活的分?jǐn)?shù)多項(xiàng)式方法(fractional polynomials model)建模。該方法可以跳過ROC曲線估計(jì),直接得到時(shí)依AUC估計(jì)量。對(duì)于模型參數(shù)的估計(jì)采用偽偏似然估計(jì)法(pseudo partial-likelihood procedure),同時(shí)采用總的一致性指標(biāo)IAUCC(τ)比較兩生物標(biāo)志物間總的預(yù)測(cè)準(zhǔn)確度。結(jié)果:Meta分析納入19篇文章,累積共有DLBCL病例1699例。各研究間無明顯的異質(zhì)性(2X=24.79,自由度df=18,P=0.131,2I=27.4%),合并總效應(yīng)量HR的值為2.04(95%CI:1.75-2.38),對(duì)結(jié)果進(jìn)行檢驗(yàn)有統(tǒng)計(jì)學(xué)意義(Z=9.24,P0.001)。隨后經(jīng)亞組分析和敏感性分析結(jié)果顯示,IRF4/MUM1是DLBCL患者預(yù)后的重要危險(xiǎn)因素。收集2014年1月初至2016年9月底山西省腫瘤醫(yī)院血液科診斷明確、隨訪資料齊全的DLBCL病例315例。將IRF4/MUM1加入IPI中,并建立一種新的0-6分的預(yù)后評(píng)分系統(tǒng)稱為腫瘤標(biāo)志物調(diào)整的IPI(T-IPI),并且探討T-IPI對(duì)DLBCL患者預(yù)后評(píng)價(jià)的預(yù)測(cè)準(zhǔn)確度。從IPI和T-IPI的AUC(t)圖形及其可信區(qū)間可見,隨著時(shí)間的變化,兩預(yù)后指標(biāo)的AUC(t)曲線都在AUC(t)=0.5的直線上方且變化較為平穩(wěn),并且明顯可見T-IPI的AUC(t)曲線在IPI之上,提示T-IPI對(duì)DLBCL的預(yù)測(cè)準(zhǔn)確度要好于IPI。為了確定這種優(yōu)勢(shì)是否具有統(tǒng)計(jì)學(xué)意義,我們檢驗(yàn)了總的一致性指標(biāo)IAUC C(τ)在IPI和T-IPI之間的差異,IAUCC(τ)的估計(jì)差異為0.138,標(biāo)準(zhǔn)誤差為0.059,得出T-IPI明顯具有比IPI更好的預(yù)測(cè)準(zhǔn)確度的結(jié)論(P=0.026)。結(jié)論:Meta分析結(jié)果和半?yún)?shù)時(shí)依AUC方法分析結(jié)果均顯示IRF4/MUM1陽性表達(dá)是DLBCL患者預(yù)后的危險(xiǎn)因素。將IRF4/MUM1加入IPI中可以有助于提高其對(duì)DLBCL患者預(yù)后的預(yù)測(cè)準(zhǔn)確度。
[Abstract]:Objective: to evaluate the prognostic value of IRF4/MUM1 expression in patients with diffuse large B-cell lymphoma (DLBCL) by semi-parametric time-dependent AUC method (AUC method). This study is divided into two parts. The first part, Meta analysis, comprehensively and quantitatively studied the relationship between IRF4/MUM1 expression and prognosis of DLBCL patients. The other part is the application of the method. The semi-parametric AUC method is used to evaluate whether the addition of a tumor marker IRF4/MUM1 will improve the prediction accuracy of international prognostic index (IPI) for the prognosis of DLBCL patients. Methods: all published Chinese and English literatures on IRF4/MUM1 and prognosis of diffuse large B-cell lymphoma were searched in Pubmed, Wanfang and CNKI databases from the establishment of the database to December 2016. The literature was read independently by two reviewers. HR and HR95CIof IRF4/MUM1 normal group and elevated group were extracted. Fixed effect model was used to combine HR and HR95 CI.The sensitivity analysis was used to estimate the change of risk ratio. In this paper, we use the semi-parametric AUC method to construct the AUC t function for time t, and use the flexible fractional polynomial method to model the fractional polynomials model. This method can skip the ROC curve estimation and get the AUC estimator directly. Pseudo partial-likelihood procedure is used to estimate the parameters of the model, and the total accuracy of prediction between the two biomarkers is compared by using the general consistency index IAUCC( 蟿). Results A total of 1699 cases of DLBCL were included in 19 articles. There was no obvious heterogeneity between the two studies, and there was no obvious heterogeneity between the two studies. The degree of freedom (dftl) was 0.131 ~ 2i ~ (2) I ~ (27. 4), and the total effect HR was 2.0495% CI: 1.75-2.38. The results were statistically significant. The subgroup analysis and sensitivity analysis showed that IRF4 / MUM1 was an important prognostic factor in DLBCL patients. From the beginning of January 2014 to the end of September 2016, 315 cases of DLBCL with definite diagnosis and complete follow-up data were collected. IRF4/MUM1 was added to IPI, and a new prognostic scoring system with 0-6 scores was established, which was called IPIT-IPIN adjusted by tumor markers. The predictive accuracy of T-IPI in evaluating the prognosis of DLBCL patients was discussed. From the IPI and T-IPI AUC t) patterns and their confidence intervals, the AUC t) curves of the two prognostic indicators were both above the straight line of AUC(t)=0.5 and changed steadily with the change of time, and it was obvious that the AUC t) curves of T-IPI were above IPI. The results suggest that the prediction accuracy of T-IPI to DLBCL is better than that of IPI. In order to determine whether this advantage is statistically significant, we tested the difference between IPI and T-IPI of the total consistency index IAUC C (蟿). The estimated difference of IAUCC (蟿) is 0.138 and the standard error is 0.059. It is concluded that T-IPI has better prediction accuracy than IPI. Conclusion the positive expression of IRF4/MUM1 was found to be a risk factor for the prognosis of patients with DLBCL. Adding IRF4/MUM1 to IPI can improve the accuracy of predicting the prognosis of DLBCL patients.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R733.1

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本文編號(hào)：1937166