Shan Tao, Lu Hongwei, Ji Hong, Li Yiming, Guo Jian, Chen Xi, Wu Tao
Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
PLoS One. 2014 Jun 20;9(6):e97239. doi: 10.1371/journal.pone.0097239. eCollection 2014.
Cancer development and progression is not only associated with the tumor cell proliferation but also depends on the interaction between tumor cells and the stromal microenvironment. A new understanding of the role of the tumor microenvironment suggests that the loss of stromal caveolin-1 (Cav-1) as a key regulator may become a potential therapy target. This study aims to elucidate whether stromal Cav-1 expression in pancreatic cancer can be a strong prognosis biomarker.
Tissue samples from 45 pancreatic cancer patients were studied. Parenchyma and stroma were separated and purified using laser capture microdissection. Stromal Cav-1 expression was measured from pancreatic cancer, paraneoplastic, and normal tissue using immunohistochemistry. We analyzed the correlation of stromal Cav-1 expression with clinicopathologic features and prognostic indicators, such as tumor marker HER-2/neu gene.
Specimens from six patients (13.3%) showed high levels of stromal Cav-1 staining, those from eight patients (17.8%) showed a lower, intermediate level of staining, whereas those from 31 patients (68.9%) showed an absence of staining. Cav-1 expression in cancer-associated fibroblasts was lower than that in paracancer-associated and in normal fibroblasts. Stromal Cav-1 loss was associated with TNM stage (P = 0.018), lymph node metastasis (P = 0.014), distant metastasis (P = 0.027), and HER-2/neu amplification (P = 0.007). The relationships of age, sex, histological grade, and tumor size with stromal Cav-1 expression were not significant (P>0.05). A negative correlation was found between circulating tumor cells and stromal Cav-1 expression (P<0.05).
The loss of stromal Cav-1 in pancreatic cancer was an independent prognostic indicator, thus suggesting that stromal Cav-1 may be an effective therapeutic target for patients with pancreatic cancer.
癌症的发生和发展不仅与肿瘤细胞增殖有关，还取决于肿瘤细胞与基质微环境之间的相互作用。对肿瘤微环境作用的新认识表明，作为关键调节因子的基质小窝蛋白-1（Cav-1）的缺失可能成为潜在的治疗靶点。本研究旨在阐明胰腺癌中基质Cav-1的表达是否可作为一个强有力的预后生物标志物。
对45例胰腺癌患者的组织样本进行研究。使用激光捕获显微切割技术分离并纯化实质和基质。采用免疫组织化学方法检测胰腺癌、癌旁组织和正常组织中基质Cav-1的表达。我们分析了基质Cav-1表达与临床病理特征及预后指标（如肿瘤标志物HER-2/neu基因）之间的相关性。
6例患者（13.3%）的样本显示基质Cav-1染色水平高，8例患者（17.8%）的样本显示较低的中等染色水平，而31例患者（68.9%）的样本显示无染色。癌相关成纤维细胞中Cav-1的表达低于癌旁相关成纤维细胞和正常成纤维细胞。基质Cav-1缺失与TNM分期（P = 0.018）、淋巴结转移（P = 0.014）、远处转移（P = 0.027）及HER-2/neu扩增（P = 0.007）相关。年龄、性别、组织学分级和肿瘤大小与基质Cav-1表达之间的关系不显著（P>0.05）。循环肿瘤细胞与基质Cav-1表达之间呈负相关（P<0.05）。
胰腺癌中基质Cav-1的缺失是一个独立的预后指标，这表明基质Cav-1可能是胰腺癌患者的有效治疗靶点。
