Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.
Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.
复制标题
DOI：
10.18632/oncotarget.2651
复制
发表时间：
2014-12-30
期刊：
影响因子：
--
通讯作者：
Koch M
中科院分区：
文献类型：
--
作者：
Kahlert C;Fiala M;Musso G;Halama N;Keim S;Mazzone M;Lasitschka F;Pecqueux M;Klupp F;Schmidt T;Rahbari N;Schölch S;Pilarsky C;Ulrich A;Schneider M;Weitz J;Koch M
胰腺癌由大量异质性肿瘤细胞和基质细胞组成，基质细胞通过释放血管生成因子促进肿瘤进展。这些因子可作为循环血清因子检测。我们对肿瘤源性和间质源性血管生成因子进行了隔室特异性分析，以确定治疗胰腺癌的生物标志物和分子靶点。对来自原发性导管腺癌（n = 51）的冷冻组织进行激光显微切割以分离肿瘤和间质组织。使用组织衍生蛋白和相应血清的多重ELISA测定分析17种血管生成因子（血管生成素-2、卵泡抑素、GCSF、HGF、白细胞介素-8、瘦素、PDGF-BB、PECAM-1、VEGF、基质金属蛋白酶-1、-2、-3、-7、-9、-10、-12和-13）的表达。我们的研究揭示了几种血管生成因子和基质金属蛋白酶的特异性表达谱。相应血清样品的ROC分析揭示MMP-7和MMP-12是诊断胰腺癌患者与健康对照供体的强分类器。单因素和多因素分析显示，肿瘤源性PDGF-BB和MMP-1的高表达与生存期延长相关。总之，血管生成细胞因子和基质金属蛋白酶在胰腺癌和周围间质中的独特表达模式可能暗示它们是癌症治疗的新靶点。肿瘤来源的PDGF-BB和MMP-1是生存不良的重要和独立的预后标志物。
Pancreatic cancer consists of a heterogenous bulk of tumor cells and stroma cells which contribute to tumor progression by releasing angiogenic factors. Those factors can be detected as circulating serum factors. We performed a compartment-specific analysis of tumor-derived and stroma-derived angiogenic factors to identify biomarkers and molecular targets for the treatment of pancreatic cancer. Kryo-frozen tissue from primary ductal adenocarcinomas (n = 51) was laser-microdissected to isolate tumor and stroma tissue. Expression of 17 angiogenic factors (angiopoietin-2, follistatin, GCSF, HGF, interleukin-8, leptin, PDGF-BB, PECAM-1, VEGF, matrix metalloproteinase -1, -2, -3, -7, -9, -10, -12, and -13) was analyzed using a multiplex elisa assay for tissue-derived proteins and corresponding serum. Our study reveals a compartment-specific expression profile for several angiogenic factors and matrix metalloproteinases. ROC analysis of corresponding serum samples reveals MMP-7 and MMP-12 as strong classifiers for the diagnosis of patients with pancreatic cancer vs. healthy control donors. High expression of tumor-derived PDGF-BB and MMP-1 correlates with prolonged survival in univariate and multivariate analysis. In conclusion, a distinct expression patterns for angiogenic cytokines and MMPs in pancreatic cancer and surrounding stroma may implicate them as novel targets for cancer treatment. Tumor-derived PDGF-BB and MMP-1 are significant and independent prognostic markers for poor survival.
登录
查看更多内容
影响因子：
50.3
作者：
Özdemir BC;Pentcheva-Hoang T;Carstens JL;Zheng X;Wu CC;Simpson TR;Laklai H;Sugimoto H;Kahlert C;Novitskiy SV;De Jesus-Acosta A;Sharma P;Heidari P;Mahmood U;Chin L;Moses HL;Weaver VM;Maitra A;Allison JP;LeBleu VS;Kalluri R
通讯作者：
Kalluri R
影响因子：
50.3
作者：
Cooke VG;LeBleu VS;Keskin D;Khan Z;O'Connell JT;Teng Y;Duncan MB;Xie L;Maeda G;Vong S;Sugimoto H;Rocha RM;Damascena A;Brentani RR;Kalluri R
通讯作者：
Kalluri R
影响因子：
5.3
作者：
Decock J;Thirkettle S;Wagstaff L;Edwards DR
通讯作者：
Edwards DR
影响因子：
24.5
作者：
Neesse, Albrecht;Michl, Patrick;Tuveson, David A.
通讯作者：
Tuveson, David A.
影响因子：
3
作者：
Delcore, R;Rodriguez, FJ;Thomas, JH
通讯作者：
Thomas, JH