Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma
Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma
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DOI：
10.1002/ijc.23611
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发表时间：
2008-09-01
影响因子：
6.4
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Kawase, Akikazu;Ishii, Genichiro;Ochiai, Atsushi
最近的研究报道了podoplanin在癌细胞和间质细胞中的表达增加，但对其在肺腺癌中的表达及其生物学意义知之甚少。我们检测了177例连续肺腺癌病例中癌细胞和间质细胞的podoplanin表达，并分析了podoplanin表达与临床病理因素和预后之间的关系。Podoplanin表达在177例中仅9例（5.1%）的癌细胞顶膜上。与此相反，癌症相关的成纤维细胞（CAFs）被发现在54例（30.5%）表达podoplanin。Podoplanin（+）CAF仅见于浸润性腺癌，而非浸润性腺癌中无表达。常规预后因素与CAFs中podoplanin表达显著相关。单因素分析和对数秩检验显示podoplanin表达与较短的生存时间显著相关（分别为p < 0.001和p < 0.001）。我们根据表达podoplanin的CAFs的比例将病例分为3组[0级组（n = 123），1级组（n = 36）和2级组（n = 18）]。结果显示，CAFs检测podoplanin表达的分级与常规预后因素显著相关。此外，2级组的生存时间往往短于I级组（p = 0.092）。这项研究的结果强调了CAFs表达podoplanin的重要性，并为肺腺癌中癌症微环境的生物学提供了新的见解。(C)2008 Wiley-Liss，Inc.
Recent studies have reported increased podoplanin expression by cancer cells and stromal cells, but little is known about its expression and biological significance in adenocarcinoma of the lung. We examined podoplanin expression by both cancer cells and stromal cells in 177 consecutive lung adenocarcinoma cases and analyzed relations between podoplanin expression and both clinicopathological factors and outcome. Podoplanin expression was observed on the apical membrane of the cancer cells in only 9 of the 177 (5.1%) cases. By contrast, cancer-associated fibroblasts (CAFs) were found to express podoplanin in 54 cases (30.5%). Podoplanin (+) CAFs were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. The univariate analyses and log-rank test showed that podoplanin expression was significantly associated with shorter survival time (p < 0.001 and p < 0.001, respectively). We divided the cases into 3 groups according grade based on the proportion of CAFs expressing podoplanin [a grade 0 group (n = 123), a grade 1 group (n = 36) and a grade 2 group (n = 18)]. The result showed that conventional prognostic factors were significantly correlated with the grade of podoplanin expression by CAFs. Furthermore, the grade 2 group tended to have a shorter survival time than the grade I group (p = 0.092). The results of this study highlight the importance of podoplanin expression by CAFs and provide new insights into the biology of the cancer microenvironment in adenocarcinoma of the lung. (C) 2008 Wiley-Liss, Inc.