Prognostic Significance of Carbonic Anhydrase IX Expression by Cancer-associated Fibroblasts in Lung Adenocarcinoma
Prognostic Significance of Carbonic Anhydrase IX Expression by Cancer-associated Fibroblasts in Lung Adenocarcinoma
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DOI：
10.1002/cncr.24303
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发表时间：
2009-06-15
期刊：
影响因子：
6.2
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Nakao, Masayuki;Ishii, Genichiro;Ochiai, Atsushi
背景：癌组织由癌细胞和几种类型的基质细胞组成，包括癌相关成纤维细胞（CAF）。碳酸酐酶（CA）IX已被用作内源性缺氧标志物，尽管据报道其在癌细胞中的表达与广泛肿瘤中的不良结局相关，但据作者所知，其在CAF中表达的生物学意义仍不清楚。方法：作者采用免疫组化方法检测了158例肺腺癌手术切除标本中CAF和癌细胞的CA IX表达。结果：CAIX在158例CAFs中表达39例（24.7%），在癌细胞中表达40例（25.3%）。CAFs的CA IX表达与传统的预后因素（包括病理肿瘤分类和淋巴结受累）显著相关。单变量分析和对数秩检验表明CAFs（分别为P= 0.006和P= 0.0052）和癌细胞（分别为P= 0.020和P= 0.0179）的CA IX表达与较低的生存率之间存在显著相关性。对这两个因素的多变量分析表明，CAFs的CA IX表达与较低的生存率之间存在统计学显著相关性（风险比[HR]，1.797; P= 0.032），但癌细胞的表达与较低的生存率之间无统计学显著相关性（HR，1.561; P= 0.102）。结论：目前的研究结果表明，CAFs的CA IX表达比癌细胞的CA IX表达更能预测结果，并为CAFs在肺腺癌缺氧微环境中的生物学意义提供了新的见解。Cancer 2009;115：2732-43. (C)2009年美国癌症协会。
BACKGROUND: Cancer tissue is comprised of cancer cells and several types of stromal cells, including cancer-associated fibroblasts (CAFs). Carbonic anhydrase (CA) IX has been used as an endogenous hypoxia marker, and although its expression by cancer cells has been reported to be associated with a poor outcome in a board range of tumors, to the authors' knowledge, the biologic significance of its expression by CAFs remains unclear. METHODS: The authors investigated CA IX expression by CAFs and cancer cells immunohistochemically in 158 consecutive resected cases of lung adenocarcinoma. RESULTS: CA IX was expressed by CAFs in 39 (24.7%) of the 158 cases and by cancer cells in 40 (25.3%) cases. CA IX expression by CAFs was found to be significantly correlated with conventional prognostic factors, including pathologic tumor classification and lymph node involvement. A univariate analysis and the log-rank test demonstrated a significant association between CA IX expression by CAFs (P=.006 and P=.0052, respectively) and by cancer cells (P=.020 and P=.0179, respectively) with lower survival rate. A multivariate analysis of these 2 factors indicated a statistically significant association between CA IX expression by CAFs and a lower survival rate (hazards ratio [HR], 1.797; P=.032), but not between expression by cancer cells and lower survival rate (HR, 1.561; P=.102). CONCLUSIONS: The findings of the current study indicate that CA IX expression by CAFs was a better predictor of outcome than CA IX expression by cancer cells and provides new insights into the biologic significance of CAFs in the hypoxic microenvironment of the lung adenocarcinoma. Cancer 2009;115:2732-43. (C) 2009 American Cancer Society.