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1、腫瘤血液標(biāo)志物的研發(fā)及臨床評(píng)價(jià)腫瘤血液標(biāo)志物的研發(fā)及臨床評(píng)價(jià)Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths by Sex, United States, 2013CA Cancer J Clin. 2013, 63(1):11-30Nature Reviews Cancer, 2011, 426-437Cell free nucleic acidsOutline of strategies for biomarker discovery through utilization of emerging
2、technologies.Nat Clin Pract Oncol. 2008,5(10):588-99Cancer biomarkers that are currently in clinical useNat Clin Pract Oncol. 2008,5(10):588-99Multi-parameter panels can significantly improve the diagnostic value compared to the conventional biomarker 8MethylationprofilingofserumDNAfromhepatocellula
3、rcarcinomapatientsusinganInfiniumHumanMethylation450BeadChip A A. . 6例早期原發(fā)性肝癌和6例健康對(duì)照的全基因組甲基化水平。 B B. . 早期原發(fā)性肝癌組和健康對(duì)照組全基因組甲基化水平比較與健康對(duì)照組相比，早期原發(fā)性肝癌組差異甲基化位點(diǎn)的個(gè)數(shù)及倍數(shù)關(guān)系與健康對(duì)照組相比，早期原發(fā)性肝癌組差異甲基化位點(diǎn)的基因分布值大于0.5為超甲基化值小于0.2為超低甲基化我們篩選出453個(gè)健康對(duì)照組和37個(gè)原發(fā)性肝細(xì)胞癌組的超甲基化位點(diǎn)。超甲基化位點(diǎn)的聚類分析(歐氏距離)超甲基化位點(diǎn)的基因本體論和基因功能富集分析 原發(fā)性肝細(xì)胞癌組中超甲基化位點(diǎn)
4、的GO及功能富集分析 健康對(duì)照組中超甲基化位點(diǎn)的GO及功能富集分析 基因功能富集分析后健康對(duì)照組中超甲基化位點(diǎn)的基因相互作用分析DBX2和THY1甲基化位點(diǎn)通過(guò)亞硫酸鹽測(cè)序法驗(yàn)證DBX2和THY1甲基化位點(diǎn)通過(guò)亞硫酸鹽測(cè)序法進(jìn)行擴(kuò)大樣本驗(yàn)證 A.A. DBX2和THY1甲基化位點(diǎn)在原發(fā)性肝癌組和健康對(duì)照組的甲基化水平比較。B.B. DBX2和THY1甲基化位點(diǎn)用于區(qū)分原發(fā)性肝癌組和健康對(duì)照組的診斷價(jià)值Multi-parametermodelfordiagnosisofcancer2129例慢性胰腺炎82例急性胰腺炎162例胰腺癌33例結(jié)腸炎62例結(jié)腸息肉101例結(jié)腸癌20例結(jié)腸癌術(shù)后40例胃增
5、生139例胃癌31例慢性肺炎28例小細(xì)胞肺癌32例肺鱗癌72例肺腺癌22例乳腺增生101例乳腺癌65例宮頸良性病變72例宮頸癌18例宮頸癌術(shù)后84例前列腺增生108例前列腺癌12例前列腺癌術(shù)后200例健康對(duì)照胰腺疾病結(jié)腸疾病胃疾病肺疾病乳腺疾病宮頸疾病前列腺疾病正常對(duì)照ALB、ALP、ALT、ApoA1、ApoB、AST、Ca、CHO、CK、CKMB、CO2、Cl、CYS、CR、DB、GGT、GLU、HDL、HCY、K、LDL、LP(a)、Mg、Na、P、SA、TP、TB、TBA、TG、UN和和UAGM-CSF、IFN-、IL-10、IL-1、IL-2、IL-4、IL-6、IL-8、MCP-1
6、和和TNFPG1、PG2和和SCCAFP、CA125、CA153、CA199、CA724、 CY211、CEA、FERR和和NSE1513例For differentiating between the colorectal adenoma and colorectal cancer groups. The AUC of multivariate logistic regression was 0.945 (95% CI: 0.9090.981). Compared with the conventional biomarkers CEA and CA199, the AUC of multi
7、variate logistic regression showed significant improvements (p 0.05). AUC: Area under the curve. FutureOncology,201326 The red line was the leave-one-out cross-validation (LOOCV) accuracy curve varying with k and each asterisk represent the value of accuracy with a fixd kROCcurvesforthetopfivefeatur
8、esandtwopanelsofbiomarkersselectedbyourmodel.Figure 1. Flowchart of our experimental designTable 1. Clinical characteristic of the studied subjectsTable 2. List of the serum parameters in the 61-plex panelTable 3. The sensitivity of top 20 performing 4 serum parameter panels for discriminating PDAC
9、Vs Control and PDAC Vs Benign group identified by MMC algorithm applied to the training set at 90% specificityFigure 2. ROC curves analysis for discriminating between the PDAC versus Control and PDAC versus Benign groups in the training group. ROC curves of CA19-9, ALB, CRP and IL-8 panel (solid lin
10、e) and CA19-9 (dotted line) for discriminating between PDAC and Ctrl in the training group (a) and validation group (c). ROC curves of the panel consisting of CA19-9, CO2, CRP and IL-6 (solid line) and CA19-9 (dotted line) for discriminating between PDAC and Benign in the training group (b) and validation group (d).33Thanksforyourattention
醫(yī)學(xué)交流課件：腫瘤血液標(biāo)志物的研發(fā)及臨床評(píng)價(jià)
