The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival.
The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival.
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DOI：
10.1186/s12885-015-1820-x
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发表时间：
2015-10-24
期刊：
影响因子：
3.8
通讯作者：
Hughes SJ
中科院分区：
文献类型：
--
作者：
Delitto D;Black BS;Sorenson HL;Knowlton AE;Thomas RM;Sarosi GA;Moldawer LL;Behrns KE;Liu C;George TJ;Trevino JG;Wallet SM;Hughes SJ
肿瘤微环境影响胰腺癌（PC）的发展，进展和转移。肿瘤内炎症介质如何调节这种生物学仍然知之甚少。我们假设PC微环境中的炎症环境与临床病理学结果和生存率相关。正常胰腺（n = 6）、慢性胰腺炎（n = 9）和胰腺癌（n = 36）的胰腺标本在切除后立即匀浆。对匀浆进行41种炎症介质的多重分析。与非恶性对照相比，腺癌标本中有23种介质显著升高。肿瘤内IL-8浓度升高与肿瘤较大（P = .045）和分化差（P = .038）相关;新辅助化疗与IL-8浓度降低相关（P = .003）。新辅助治疗也与Flt-3 L浓度升高相关（P = .005）。促炎细胞因子IL-1β（P = 0.017）和TNFα（P = 0.033）水平升高与新辅助治疗的组织病理学反应不良相关。G-CSF（P = 0.016）和PDGF-AA（P = 0.012）浓度升高与总生存率降低相关。相反，FGF-2（P = 0.038）、TNFα（P = 0.031）和MIP-1α（P = 0.036）浓度升高与生存期延长相关。胰腺癌微环境具有独特的炎症环境，具有潜在的诊断和预后价值。
The tumor microenvironment impacts pancreatic cancer (PC) development, progression and metastasis. How intratumoral inflammatory mediators modulate this biology remains poorly understood. We hypothesized that the inflammatory milieu within the PC microenvironment would correlate with clinicopathologic findings and survival. Pancreatic specimens from normal pancreas (n = 6), chronic pancreatitis (n = 9) and pancreatic adenocarcinoma (n = 36) were homogenized immediately upon resection. Homogenates were subjected to multiplex analysis of 41 inflammatory mediators. Twenty-three mediators were significantly elevated in adenocarcinoma specimens compared to nonmalignant controls. Increased intratumoral IL-8 concentrations associated with larger tumors (P = .045) and poor differentiation (P = .038); the administration of neoadjuvant chemotherapy associated with reduced IL-8 concentrations (P = .003). Neoadjuvant therapy was also associated with elevated concentrations of Flt-3 L (P = .005). Elevated levels of pro-inflammatory cytokines IL-1β (P = .017) and TNFα (P = .033) were associated with a poor histopathologic response to neoadjuvant therapy. Elevated concentrations of G-CSF (P = .016) and PDGF-AA (P = .012) correlated with reduced overall survival. Conversely, elevated concentrations of FGF-2 (P = .038), TNFα (P = .031) and MIP-1α (P = .036) were associated with prolonged survival. The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value.