Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.
Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.
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DOI：
10.1186/1471-2407-13-404
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发表时间：
2013-09-03
期刊：
影响因子：
3.8
通讯作者：
Diamandis EP
中科院分区：
文献类型：
--
作者：
Makawita S;Dimitromanolakis A;Soosaipillai A;Soleas I;Chan A;Gallinger S;Haun RS;Blasutig IM;Diamandis EP
寻找高灵敏度、高特异性的新的血清标志物是胰腺癌研究的重要方向。通过对胰腺癌细胞株和胰液的广泛蛋白质组学分析，我们先前生成了一份候选胰腺癌生物标志物的清单。本研究详细说明了我们之前确定的四个候选基因的进一步验证：再生胰岛衍生1β(REG1B)、突触素(SYCN)、前梯度同源蛋白2(AGR2)和赖氨酰氧化酶样蛋白2(LOXL2)。用酶联免疫吸附试验对两组样本的血清/血浆进行验证，样本组A：胰腺导管腺癌(n = 100)，健康(n = 92)；样本B：胰腺导管腺癌(n = 82)，良性(n = 41)，无病(n = 47)，其他癌症(n = 70)。在两个样本组中分别评估生物标记物在区分PDAC和每个对照组方面的表现。随后，应用多参数模型来评估所有可能的两个和三个标记板在区分PDAC和无疾病对照方面的能力。使用样本组B建立模型，然后在样本组A中进行验证。单独地，在至少一个样本组中，所有标记物均显著高于健康对照组(p ≤ 0.01)。与良性对照组相比，PDAC中SYCN、REG1B和AGR2显著升高(p ≤ 0.0 1)，与其他肿瘤相比，PDAC中AGR2显著升高(p 和 0.0 1)。同时对CA19.9进行评估。单独地，CA19.9在受试者工作特征(ROC)分析中显示出最大的曲线下面积(AUC)；然而，当结合分析时，三个小组(CA19.9 + REG1B(AUC0.88)，CA19.9 + SYCN + REG1B(AUC0.87)和CA19.9 + AGR2 + REG1B(AUC0.87))显示的AUC显著大于单独CA19.9的AUC(p <； 0.05)。在早期(I-II期)PDAC与无疾病对照组的比较中，SYCN + REG1B + CA19.9的组合在两个样本组中显示出最大的AUC值(A组和B组的AUC值分别为0.87和0.92)。其他血清生物标志物，特别是SYCN和REG1B，当与CA19.9结合时，显示出作为改善胰腺癌诊断指标的前景，因此值得进一步验证。
The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient homolog 2 protein (AGR2), and lysyl oxidase-like 2 (LOXL2). The candidate biomarkers were validated using enzyme-linked immunosorbent assays in two sample sets of serum/plasma comprising a total of 432 samples (Sample Set A: pancreatic ductal adenocarcinoma (PDAC, n = 100), healthy (n = 92); Sample Set B: PDAC (n = 82), benign (n = 41), disease-free (n = 47), other cancers (n = 70)). Biomarker performance in distinguishing PDAC from each control group was assessed individually in the two sample sets. Subsequently, multiparametric modeling was applied to assess the ability of all possible two and three marker panels in distinguishing PDAC from disease-free controls. The models were generated using sample set B, and then validated in Sample Set A. Individually, all markers were significantly elevated in PDAC compared to healthy controls in at least one sample set (p ≤ 0.01). SYCN, REG1B and AGR2 were also significantly elevated in PDAC compared to benign controls (p ≤ 0.01), and AGR2 was significantly elevated in PDAC compared to other cancers (p < 0.01). CA19.9 was also assessed. Individually, CA19.9 showed the greatest area under the curve (AUC) in receiver operating characteristic (ROC) analysis when compared to the tested candidates; however when analyzed in combination, three panels (CA19.9 + REG1B (AUC of 0.88), CA19.9 + SYCN + REG1B (AUC of 0.87) and CA19.9 + AGR2 + REG1B (AUC of 0.87)) showed an AUC that was significantly greater (p < 0.05) than that of CA19.9 alone (AUC of 0.82). In a comparison of early-stage (Stage I-II) PDAC to disease free controls, the combination of SYCN + REG1B + CA19.9 showed the greatest AUC in both sample sets, (AUC of 0.87 and 0.92 in Sets A and B, respectively). Additional serum biomarkers, particularly SYCN and REG1B, when combined with CA19.9, show promise as improved diagnostic indicators of pancreatic cancer, which therefore warrants further validation.
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影响因子：
15.8
作者：
Faca VM;Song KS;Wang H;Zhang Q;Krasnoselsky AL;Newcomb LF;Plentz RR;Gurumurthy S;Redston MS;Pitteri SJ;Pereira-Faca SR;Ireton RC;Katayama H;Glukhova V;Phanstiel D;Brenner DE;Anderson MA;Misek D;Scholler N;Urban ND;Barnett MJ;Edelstein C;Goodman GE;Thornquist MD;McIntosh MW;DePinho RA;Bardeesy N;Hanash SM
通讯作者：
Hanash SM
影响因子：
1.3
作者：
Lv, Shunli;Gao, Jun;Ma, Lie
通讯作者：
Ma, Lie
影响因子：
7
作者：
Makawita, Shalini;Smith, Chris;Diamandis, Eleftherios P.
通讯作者：
Diamandis, Eleftherios P.
DOI：
10.1016/s1570-9639(03)00053-0
发表时间：
2003-04-11
影响因子：
3.2
作者：
Molnar, J;Fong, KSK;Csiszar, K
通讯作者：
Csiszar, K
前梯度2在胰腺癌的发展过程中表达和分泌，并促进癌细胞的存活。
影响因子：
11.2
作者：
Ramachandran V;Arumugam T;Wang H;Logsdon CD
通讯作者：
Logsdon CD