Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation

作者：Liu Zhenqiu; Beach Jessica A; Agadjanian Hasmik; Jia Dongyu; Aspuria Paul Joseph; Karlan Beth Y; Orsulic Sandra^*

来源：Gynecologic Oncology, 2015, 139(3): 394-400.

DOI：10.1016/j.ygyno.2015.08.026

• Cancer-associated stroma
• Cytoreductive surgery
• Debulking
• Desmoplasia
• Epithelial-mesenchymal transition
• Invasion
• Metastasis
• Ovarian cancer

Objective. 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.
Methods. 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.
Results. 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.
Conclusion. 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.

• 出版日期2015-12