Clinical implications and diagnostic usefulness of correlation between soluble major histocompatibility complex class I chain-related molecule a and protumorigenic cytokines in pancreatic ductal adenocarcinoma
Clinical implications and diagnostic usefulness of correlation between soluble major histocompatibility complex class I chain-related molecule a and protumorigenic cytokines in pancreatic ductal adenocarcinoma
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DOI：
10.1002/cncr.27669
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发表时间：
2013-01-01
期刊：
影响因子：
6.2
通讯作者：
Lim, Jong-Baeck
中科院分区：
文献类型：
--
作者：
Chung, Hye Won;Jang, Sunphil;Lim, Jong-Baeck
背景技术背景：肿瘤源性可溶性因子作为肿瘤与周围微环境之间的介质，在一个复杂的网络下促进肿瘤的生长和转移。本研究的目的是评估可溶性主要组织相容性复合物I类链相关分子A（sMICA）和4类细胞因子（肿瘤相关促炎、抗炎、趋化/促血管生成和生长刺激）在胰腺导管腺癌（PDAC）发生和发展中的关系。方法：分别采用酶联免疫吸附法和荧光免疫法检测134例患者（正常组55例，慢性胰腺炎组25例，PDAC组54例）血清sMICA和4类细胞因子水平。评估了sMICA和肿瘤相关细胞因子的临床意义、相关性以及在PDAC中的诊断价值。结果：血清sMICA与PDAC的发生、发展有关，与干扰素-？与PDAC的发生呈负相关（P = 0.024），而与抗炎细胞因子白细胞介素-10（IL-10）和IL-1受体拮抗剂以及双功能细胞因子肿瘤坏死因子α呈正相关（P <0.05）。sMICA还与趋化/促血管生成细胞因子血管内皮生长因子、可溶性CD 40配体和IL-8以及肿瘤生长刺激细胞因子表皮生长因子和转化生长因子α在PDAC的发生和/或进展方面呈正相关。Logistic回归分析验证了联合使用sMICA及其相关细胞因子对预测PDAC的存在和PDAC中的远处转移的诊断有用性，优于碳水化合物抗原19-9，上级。结论：sMICA可能通过影响相应的细胞因子以及在PDAC的发展和进展中引起自然杀伤细胞的细胞毒性受损而直接或间接地参与肿瘤相关的血管生成和肿瘤生长。sMICA及其相关细胞因子的组合在PDAC中表现出显着的诊断潜力。癌症2013年。(c)2012年美国癌症协会
BACKGROUND: Tumor-derived soluble factors serve as mediators between tumors and surrounding microenvironment to promote tumor growth and metastasis under a complex network. The objective of this study was to evaluate the relationships between soluble major histocompatibility complex class I chain-related molecule A (sMICA) and 4 categories of cytokines (tumor-related proinflammatory, anti-inflammatory, chemotactic/proangiogenic, and growth-stimulatory) in the development and progression of pancreatic ductal adenocarcinoma (PDAC). METHODS: Serum levels of sMICA and 4-categorized cytokines were measured by enzyme-linked immunosorbent assay and chemiluminescent immunoassay, respectively, in 134 individuals (normal, n = 55; chronic pancreatitis, n = 25; PDAC, n = 54). Clinical implications of sMICA and tumor-related cytokines, their correlations, and diagnostic usefulness in PDAC were evaluated. RESULTS: Serum sMICA, which was associated with the development and progression of PDAC, correlated with interferon-? negatively (P = 0.024), whereas it correlated positively with the anti-inflammatory cytokines interleukin-10 (IL-10) and IL-1 receptor antagonist, and the bifunctional cytokine tumor necrosis factor a, with respect to PDAC development (P < .05). sMICA also correlated positively with the chemotactic/proangiogenic cytokines vascular endothelial growth factor, soluble CD40 ligand, and IL-8, and the tumor growth-stimulatory cytokines epidermal growth factor and transforming growth factor a, with respect to PDAC development and/or progression. Logistic regression analysis validated the diagnostic usefulness of combination use of sMICA and its related cytokines to predict the presence of PDAC and distant metastasis in PDAC, superior to carbohydrate antigen 19-9. CONCLUSIONS: sMICA may be involved in tumor-associated angiogenesis and tumor growth either directly or indirectly by affecting corresponding cytokines as well as causing impairment of natural killer cell cytotoxicity in the development and progression of PDAC. A combination of sMICA and its related cytokines exhibited remarkable diagnostic potential in PDAC. Cancer 2013. (c) 2012 American Cancer Society.