A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas.
A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas.
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DOI：
10.3389/fcell.2018.00098
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发表时间：
2018
影响因子：
5.5
通讯作者：
Orsulic S
中科院分区：
文献类型：
--
作者：
Haro M;Orsulic S
肿瘤微环境越来越被认为是肿瘤进展的积极参与者。最近的一项泛癌症基因组图谱分析显示，代表肿瘤微环境成分的基因签名是可靠的生存预测因子。代表成纤维细胞和细胞外基质成分的间质基因特征与弥漫性大B细胞淋巴瘤(DLBCL)的良好存活率有关。矛盾的是，一个密切相关的基因标记已被证明与乳腺癌、卵巢癌、胰腺癌和结直肠癌等癌症患者的低存活率相关。到目前为止，还没有解释这种与DLBCL和癌症的生存结果相反的负相关性。利用公开的基因数据集，我们证实DLBCL间质基因特征与DLBCL和其他几种B细胞淋巴瘤的良好生存相关，而它与卵巢癌和其他几种实体瘤的低生存相关。我们发现DLBCL基质基因特征在正常淋巴结的淋巴成纤维细胞和卵巢癌的肿瘤相关成纤维细胞(CAF)中丰富。基于这些发现，我们提出了几种可能的机制，通过这些机制，CAF可能有助于B细胞淋巴瘤和癌症相反的生存结果。
The tumor microenvironment is increasingly recognized as an active participant in tumor progression. A recent pan-cancer genomic profile analysis has revealed that gene signatures representing components of the tumor microenvironment are robust predictors of survival. A stromal gene signature representing fibroblasts and extracellular matrix components has been associated with good survival in diffuse large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature has been shown to correlate with poor survival in carcinomas, including breast, ovarian, pancreatic, and colorectal cancer. To date, there has been no explanation for this paradoxical inverse correlation with survival outcomes in DLBCL and carcinomas. Using public gene data sets, we confirm that the DLBCL stromal gene signature is associated with good survival in DLBCL and several other B-cell lymphomas while it is associated with poor survival in ovarian cancer and several other solid tumors. We show that the DLBCL stromal gene signature is enriched in lymphoid fibroblasts in normal lymph nodes and in cancer-associated fibroblasts (CAFs) in ovarian cancer. Based on these findings, we propose several possible mechanisms by which CAFs may contribute to opposite survival outcomes in B-cell lymphomas and carcinomas.