The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.
The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.
复制标题
食管鳞状细胞癌中癌症相关成纤维细胞的预后意义。
DOI：
10.1371/journal.pone.0099955
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kim SH
中科院分区：
文献类型：
--
作者：
Ha SY;Yeo SY;Xuan YH;Kim SH
癌症相关成纤维细胞（CAF）是癌症基质中活化的成纤维细胞，在癌症进展中起重要作用。一些报道指出CAF标志物的表达与几种癌症的不良预后之间的相关性。然而，目前还没有研究食管鳞状细胞癌（ESCC）中CAF表型及其临床意义的报道。我们在116例ESCC组织标本中，基于组织学和五种CAF标志物如成纤维细胞活化蛋白（FAP）、平滑肌肌动蛋白（SMA）、成纤维细胞特异性蛋白-1（FSP 1）、血小板衍生生长因子受体（PDGFRα）和PDGFRβ的免疫组化表达，研究了ESCC的CAF表型。此外，我们还研究了CAF表型与临床相关性以及其他癌症微环境相关因素的相关性。组织学上不成熟的CAF表型与不良预后相关（p<0.001），并与微血管密度增加、肿瘤相关巨噬细胞增加和上皮向间质转化相关。CAF标记物特征性地表达于与肿瘤细胞接近的间质成纤维细胞中，并且5种CAF标记物在每个个体病例中的表达模式高度异质。在5种CAF标志物中，SMA、FSP 1和PDGFRα是ESCC的不良预后指标。未成熟CAF的食管鳞癌CAF标记阳性率明显高于成熟CAF的食管鳞癌。我们的研究结果表明，CAF表型的组织学分类是一个可靠的和重要的预后预测ESCC。CAF标志物有可能成为食管鳞癌诊断和治疗的靶点。
Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC). We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP), smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived growth factor receptor (PDGFRα), and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001) and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.
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影响因子：
3.1
作者：
Kubota, Yutaro;Kaneko, Kazuhiro;Imawari, Michio
通讯作者：
Imawari, Michio
影响因子：
7.4
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Mukherjee S;Roth MJ;Dawsey SM;Yan W;Rodriguez-Canales J;Erickson HS;Hu N;Goldstein AM;Taylor PR;Richardson AM;Tangrea MA;Chuaqui RF;Emmert-Buck MR
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Emmert-Buck MR
影响因子：
3.7
作者：
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通讯作者：
Ostman A
影响因子：
24.5
作者：
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通讯作者：
Talbot, IC
影响因子：
6
作者：
Sung, Chang Ohk;Lee, Keun-Woo;Kim, Seok-Hyung
通讯作者：
Kim, Seok-Hyung