NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer.
OBJECTIVE
Nua kinase 1 (NUAK1) was identified in multigene signatures of survival and suboptimal debulking in high-grade serous ovarian cancer (HGSOC). This study investigates the individual clinical and biologic contributions of NUAK1 in HGSOC patients and cell lines.


METHODS
Public transcript expression, clinical, and outcome data were used to interrogate the relationship between NUAK1 and clinicopathologic factors and patient outcomes including progression-free survival (PFS) and molecular subtypes using logistic and Cox modeling. Analysis of NUAK1 transcript expression was performed in primary tumors from 34 HGSOC patients with < or ≥2 years PFS. The impact of silencing NUAK1 by RNA interference (RNAi) on the migratory potential and chemosensitivity of SOC cells was assessedin vitro.


RESULTS
Elevated NUAK1 transcript expression was associated with worse PFS (hazard ratio = 1.134), advanced stage (odds ratio, OR = 1.7), any residual disease (OR = 1.58), and mesenchymal disease subtype (OR = 7.79 ± 5.89). Elevated NUAK1 transcript expression was observed in HGSOC patients with < vs. ≥2 years PFS (p< 0.045). RNAi-mediated silencing of NUAK1 expression attenuated migration of OV90 and E3 HGSOC cellsin vitro, but did not modulate sensitivity to cisplatin or paclitaxel.


CONCLUSIONS
Elevated NUAK1 was associated with poor survival as well as advanced stage, residual disease after cytoreductive surgery and mesenchymal molecular subtype. NUAK1 impacted migration, but not chemosensitivity,in vitro. Additional studies are needed to further develop the concept of NUAK1 as a clinically deployable biomarker and therapeutic target in HGSOC.
National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA; Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA.
Neil T
NT
Phippen
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA; Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Nicholas W
NW
Bateman
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Guisong
G
Wang
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Kelly A
KA
Conrads
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Wei
W
Ao
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Pang-Ning
PN
Teng
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Tracy A
TA
Litzi
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System , Annandale, VA , USA.
Julie
J
Oliver
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA; Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, Falls Church, VA, USA; Inova Center for Personalized Health, Inova Fairfax Hospital, Falls Church, VA, USA.
G Larry
GL
Maxwell
National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA; Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA; Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Chad A
CA
Hamilton
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA; Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Kathleen M
KM
Darcy
Department of Defense Gynecologic Cancer Center of Excellence, Women's Health Integrated Research Center at Inova Health System, Annandale, VA, USA; Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA; Department of Obstetrics and Gynecology, Inova Fairfax Medical Campus, Falls Church, VA, USA; Inova Center for Personalized Health, Inova Fairfax Hospital, Falls Church, VA, USA.
Thomas P
TP
Conrads
ARK5; NUAK1; gene expression; migration; ovarian cancer; prognosis; survival