Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation.
Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation.
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DOI：
10.1016/j.ygyno.2015.08.026
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发表时间：
2015-12
影响因子：
4.7
通讯作者：
Orsulic S
中科院分区：
文献类型：
--
作者：
Liu Z;Beach JA;Agadjanian H;Jia D;Aspuria PJ;Karlan BY;Orsulic S
晚期上皮性卵巢癌（EOC）的细胞减灭术不理想与生存率低相关，但尚不清楚不良结果是否是由于不可切除肿瘤的内在生物学或手术力度不足导致残留的肿瘤维持克隆所致。我们的目标是确定可能导致手术切除效果欠佳的潜在分子途径和细胞类型。通过比较最佳和次优细胞减灭术患者的基因表达，我们确定了与次优细胞减灭术相关的基因网络，并探索了与该基因网络相关的生物过程和细胞类型。我们发现来自次优细胞减灭术患者的原发性肿瘤表达的分子特征通常存在于 EOC 的独特分子亚型中，其特征是基质活化和淋巴血管侵袭增加。 EOC 转移瘤中存在类似的分子途径，表明细胞减灭效果不佳的患者中的原发性肿瘤在生物学上与转移性肿瘤相似。我们证明次优细胞减灭网络基因富集在反应性肿瘤基质细胞而不是恶性肿瘤细胞中。我们的数据表明，肿瘤细胞减灭术的成功取决于肿瘤生物学，例如广泛的基质反应和侵袭性增加，这可能会阻碍手术切除并最终导致生存不良。
Suboptimal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) is associated with poor survival but it is unknown if poor outcome is due to the intrinsic biology of unresectable tumors or insufficient surgical effort resulting in residual tumor-sustaining clones. Our objective was to identify the potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal surgical resection. By comparing gene expression in optimally and suboptimally cytoreduced patients, we identified a gene network associated with suboptimal cytoreduction and explored the biological processes and cell types associated with this gene network. We show that primary tumors from suboptimally cytoreduced patients express molecular signatures that are typically present in a distinct molecular subtype of EOC characterized by increased stromal activation and lymphovascular invasion. Similar molecular pathways are present in EOC metastases, suggesting that primary tumors in suboptimally cytoreduced patients are biologically similar to metastatic tumors. We demonstrate that the suboptimal cytoreduction network genes are enriched in reactive tumor stroma cells rather than malignant tumor cells. Our data suggest that the success of cytoreductive surgery is dictated by tumor biology, such as extensive stromal reaction and increased invasiveness, which may hinder surgical resection and ultimately lead to poor survival.