Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer

Chel Hun Choi, Tae Heung Kang, Joon Seon Song, Young Seob Kim, Eun Joo Chung, Kris Ylaya, Seokho Kim, Sang Seok Koh, Joon Yong Chung, Jae Hoon Kim, Stephen M. Hewitt

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Abstract

Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like receptors (TLRs) and has been reported to be involved in pancreatic tumor development. However, the significance of PAUF expression in epithelial ovarian cancer remains unclear. We aimed to investigate the possible clinical significance of PAUF in epithelial ovarian cancer. We examined the link between PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by immunohistochemistry on tissue microarray of 408 ovarian samples ranging from normal to metastatic. PAUF expression positively correlated with TLR4 expression. Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001). Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high expression are independent prognostic factor for progression-free survival, while TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for overall survival. Our results suggest that PAUF has a role in ovarian cancer progression and is a potential prognostic marker and novel chemotherapeutic target for ovarian cancer.

Original languageEnglish
Article number12161
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Adenocarcinoma
Ovarian Neoplasms
Neoplasms
Ovarian epithelial cancer
Cell Line
Toll-Like Receptors
Disease-Free Survival
Multivariate Analysis
Immunohistochemistry
Cell Proliferation
Ligands

All Science Journal Classification (ASJC) codes

  • General

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Choi, Chel Hun ; Kang, Tae Heung ; Song, Joon Seon ; Kim, Young Seob ; Chung, Eun Joo ; Ylaya, Kris ; Kim, Seokho ; Koh, Sang Seok ; Chung, Joon Yong ; Kim, Jae Hoon ; Hewitt, Stephen M. / Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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abstract = "Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like receptors (TLRs) and has been reported to be involved in pancreatic tumor development. However, the significance of PAUF expression in epithelial ovarian cancer remains unclear. We aimed to investigate the possible clinical significance of PAUF in epithelial ovarian cancer. We examined the link between PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by immunohistochemistry on tissue microarray of 408 ovarian samples ranging from normal to metastatic. PAUF expression positively correlated with TLR4 expression. Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001). Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high expression are independent prognostic factor for progression-free survival, while TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for overall survival. Our results suggest that PAUF has a role in ovarian cancer progression and is a potential prognostic marker and novel chemotherapeutic target for ovarian cancer.",
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Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer. / Choi, Chel Hun; Kang, Tae Heung; Song, Joon Seon; Kim, Young Seob; Chung, Eun Joo; Ylaya, Kris; Kim, Seokho; Koh, Sang Seok; Chung, Joon Yong; Kim, Jae Hoon; Hewitt, Stephen M.

In: Scientific reports, Vol. 8, No. 1, 12161, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer

AU - Choi, Chel Hun

AU - Kang, Tae Heung

AU - Song, Joon Seon

AU - Kim, Young Seob

AU - Chung, Eun Joo

AU - Ylaya, Kris

AU - Kim, Seokho

AU - Koh, Sang Seok

AU - Chung, Joon Yong

AU - Kim, Jae Hoon

AU - Hewitt, Stephen M.

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N2 - Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like receptors (TLRs) and has been reported to be involved in pancreatic tumor development. However, the significance of PAUF expression in epithelial ovarian cancer remains unclear. We aimed to investigate the possible clinical significance of PAUF in epithelial ovarian cancer. We examined the link between PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by immunohistochemistry on tissue microarray of 408 ovarian samples ranging from normal to metastatic. PAUF expression positively correlated with TLR4 expression. Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001). Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high expression are independent prognostic factor for progression-free survival, while TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for overall survival. Our results suggest that PAUF has a role in ovarian cancer progression and is a potential prognostic marker and novel chemotherapeutic target for ovarian cancer.

AB - Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like receptors (TLRs) and has been reported to be involved in pancreatic tumor development. However, the significance of PAUF expression in epithelial ovarian cancer remains unclear. We aimed to investigate the possible clinical significance of PAUF in epithelial ovarian cancer. We examined the link between PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by immunohistochemistry on tissue microarray of 408 ovarian samples ranging from normal to metastatic. PAUF expression positively correlated with TLR4 expression. Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001). Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high expression are independent prognostic factor for progression-free survival, while TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for overall survival. Our results suggest that PAUF has a role in ovarian cancer progression and is a potential prognostic marker and novel chemotherapeutic target for ovarian cancer.

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