title: REDD1 and p-AKT over-expression may predict poor prognosis in ovarian cancer.
abstract: We investigated the clinical significance of regulated in development and DNA damage response (REDD1) and p-AKT expression in human ovarian cancer (OC), explored the correlation of KRAS mutations with REDD1 expression, and assessed the therapeutic relevance of REDD1 in OC. We collected and immunohistochemically analyzed 118 formalin-fixed paraffin-embedded tumor tissue samples (100 primary OC and 18 borderline tumors) and 14 normal fallopian tubes, for REDD1 and p-AKT expression. Direct DNA sequencing for KRAS mutations and quantitative real-time polymerase chain reaction for detecting REDD1 mRNA expression were performed. REDD1 and p-AKT expressions were significantly higher in serous adenocarcinoma than other histological types, and this increase positively correlated with late-stage disease. REDD1 expression correlated with ascites formation, while p-AKT expression correlated with higher histological grade and chemoresistance. Kaplan Meier survival analysis showed significantly reduced disease-free survival (DFS) and overall survival (OS) in OC patients with both REDD1 and p-AKT overexpression. Patients with KRAS mutations had a longer DFS and OS. However, KRAS mutation and REDD1 over-expression was not correlated. Together, REDD1 and p-AKT over-expression may serve as a prognostic biomarker in OC, but KRAS mutations and REDD1 protein over-expression were not correlated in OC. We believe that with increasing knowledge of the role of REDD1 in cell migration, invasion, and proliferation pathways, the potential of REDD1 as a therapeutic target in OC may be uncovered.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Pathology, Shanghai Cancer Hospital of Fudan University Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China ; Department of Pathology, The People's Hospital of Puyang Puyang City, Henan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China ; Department of Gynecology & Obstetrics, The Third Affiliated Hospital of Luohe Higher Medical School Luohe, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Jinze
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Gynecology & Obstetrics, The First Affiliated Hospital of Shihezi University School of Medicine Shihezi, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C469991:DDIT4 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS mutation; REDD1; biomarker; ovarian cancer; p-AKT; prognosis