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

Zhenqiu Liu, Jessica A. Beach, Hasmik Agadjanian, Dongyu Jia, Paul Joseph Aspuria, Beth Y. Karlan, Sandra Orsulic

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)394-400
Number of pages7
JournalGynecologic Oncology
Volume139
Issue number3
DOIs
StatePublished - Dec 1 2015

Fingerprint

Carcinoma
Gene Regulatory Networks
Neoplasms
Biological Phenomena
Survival
Residual Neoplasm
Clone Cells
Neoplasm Metastasis
Gene Expression
Ovarian epithelial cancer

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

Liu, Zhenqiu ; Beach, Jessica A. ; Agadjanian, Hasmik ; Jia, Dongyu ; Aspuria, Paul Joseph ; Karlan, Beth Y. ; Orsulic, Sandra. / Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation. In: Gynecologic Oncology. 2015 ; Vol. 139, No. 3. pp. 394-400.
@article{63836fae39c94a27b43dd41aa981402f,
title = "Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation",
abstract = "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.",
author = "Zhenqiu Liu and Beach, {Jessica A.} and Hasmik Agadjanian and Dongyu Jia and Aspuria, {Paul Joseph} and Karlan, {Beth Y.} and Sandra Orsulic",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.ygyno.2015.08.026",
language = "English (US)",
volume = "139",
pages = "394--400",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "3",

}

Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation. / Liu, Zhenqiu; Beach, Jessica A.; Agadjanian, Hasmik; Jia, Dongyu; Aspuria, Paul Joseph; Karlan, Beth Y.; Orsulic, Sandra.

In: Gynecologic Oncology, Vol. 139, No. 3, 01.12.2015, p. 394-400.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation

AU - Liu, Zhenqiu

AU - Beach, Jessica A.

AU - Agadjanian, Hasmik

AU - Jia, Dongyu

AU - Aspuria, Paul Joseph

AU - Karlan, Beth Y.

AU - Orsulic, Sandra

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84949726339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949726339&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2015.08.026

DO - 10.1016/j.ygyno.2015.08.026

M3 - Article

C2 - 26348314

AN - SCOPUS:84949726339

VL - 139

SP - 394

EP - 400

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -