Podoplanin, α-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers.
Podoplanin, α-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers.
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DOI：
10.3346/jkms.2013.28.9.1293
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发表时间：
2013-09
影响因子：
4.5
通讯作者：
Park SM
中科院分区：
文献类型：
--
作者：
Choi SY;Sung R;Lee SJ;Lee TG;Kim N;Yoon SM;Lee EJ;Chae HB;Youn SJ;Park SM
肿瘤微环境和肿瘤细胞之间的相互作用决定了原发肿瘤的行为。癌症相关成纤维细胞 (CAF) 是否具有肿瘤进展作用或保护作用可能取决于肿瘤细胞的类型和 CAF 亚群。在本研究中，我们分析了 CAF 亚群在结直肠癌 (CRC) 中的预后意义。使用抗足足蛋白 (PDPN)、α-平滑肌肌动蛋白 (α-SMA) 和 S100A4 抗体对 302 名 CRC 患者的 CAF 表型进行了分析。评估 CAF 表型与 11 项临床病理参数之间的关系，并从无病生存时间和总生存时间分析其预后意义。我们观察到，在肿瘤侵袭前沿，40%的病例存在PDPN CAF，所有病例均检测到S100A4或α-SMA CAF。分别在 10% 和 40% 的病例中观察到 PDPN/S100A4 和 α-SMA/S100A4 双染色 CAF。 PDPN+ CAF 与 6 个有利的临床病理参数和延长的无病生存时间相关。 PDPN-/α-SMAhigh CAF 与 6 种侵袭性临床病理参数相关，并且往往表现出较短的无病生存时间。另一方面，PDPN-/S100A4high CAF 与 2 个肿瘤进展参数相关，但与疾病预后无关。 PDPN+ CAF 表型与 α-SMA 或 S100A4 CAF 不同，因为它与侵袭性较低的肿瘤和良好的预后相关，而 PDPN-/α-SMAhigh 或 PDPN-/S100A4high CAF 与 CRC 中的肿瘤进展相关。这些发现表明，CAF 可以成为 CRC 中有用的预后生物标志物或抗癌治疗的潜在靶标。
The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), α-smooth muscle actin (α-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or α-SMA CAFs were detected in all the cases. PDPN/S100A4 and α-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/α-SMAhigh CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4high CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the α-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/α-SMAhigh or PDPN-/S100A4high CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.