胰腺癌微环境中的炎性环境与临床病理参数、化疗耐药性及生存率相关。
The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival.
作者信息
Delitto Daniel, Black Brian S, Sorenson Heather L, Knowlton Andrea E, Thomas Ryan M, Sarosi George A, Moldawer Lyle L, Behrns Kevin E, Liu Chen, George Thomas J, Trevino Jose G, Wallet Shannon M, Hughes Steven J
机构信息
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA.
Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL, 32610, USA.
出版信息
BMC Cancer. 2015 Oct 24;15:783. doi: 10.1186/s12885-015-1820-x.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value.
背景
肿瘤微环境影响胰腺癌（PC）的发生、发展和转移。肿瘤内炎症介质如何调节这一生物学过程仍知之甚少。我们假设PC微环境中的炎症环境与临床病理结果及生存相关。
方法
来自正常胰腺（n = 6）、慢性胰腺炎（n = 9）和胰腺腺癌（n = 36）的胰腺标本在切除后立即进行匀浆。匀浆进行41种炎症介质的多重分析。
结果
与非恶性对照相比，腺癌标本中有23种介质显著升高。肿瘤内白细胞介素-8（IL-8）浓度升高与肿瘤较大（P = 0.045）和分化差（P = 0.038）相关；新辅助化疗与IL-8浓度降低相关（P = 0.003）。新辅助治疗还与Flt-3配体（Flt-3 L）浓度升高相关（P = 0.005）。促炎细胞因子白细胞介素-1β（IL-1β，P = 0.017）和肿瘤坏死因子α（TNFα，P = 0.033）水平升高与新辅助治疗的组织病理学反应差相关。粒细胞集落刺激因子（G-CSF，P = 0.016）和血小板衍生生长因子-AA（PDGF-AA，P = 0.012）浓度升高与总生存期缩短相关。相反，成纤维细胞生长因子-2（FGF-2，P = 0.038）、TNFα（P = 0.031）和巨噬细胞炎性蛋白-1α（MIP-1α，P = 0.036）浓度升高与生存期延长相关。
结论
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。
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