title: Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation.
abstract: Ovarian cancer is the most lethal gynecologic malignancy, and clear cell adenocarcinoma of the ovary (OCCA), in particular, has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Chromobox (CBX) 7 is a polycomb repressive complex 1 component that prolongs the lifespan of normal human cells by downregulating the INK4a/ARF expression which promotes cell-cycle progression. However, recent reports studying the relationship between CBX7 expression and patient survival have differed regarding the tumor cell origins, and the precise role of CBX7 in human carcinomas remains obscure. In this study, we analyzed CBX7 expression by immunohistochemistry in 81 OCCA patients and evaluated its association with their clinical outcomes. Both the overall and progression-free survival rates of the CBX7-positive patients were significantly shorter than those of the CBX7-negative patients (p < 0.05). CBX7 knockdown experiments using two OCCA cell lines, TOV21G and KOC-7C, revealed that cell viability was significantly reduced compared to the control cells (p < 0.001). Expression microarray analysis revealed that apoptosis-related genes, particularly tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were significantly upregulated in CBX7 knockdown cells (p < 0.01). We further confirmed that CBX7 knockdown resulted in TRAIL-induced apoptosis in the OCCA cells. Thus, in this study, we showed for the first time that CBX7 was associated with a decreased OCCA prognosis. We also successfully demonstrated that the TRAIL pathway is a novel target for CBX7 expression modulation in these cells, and therapeutic agents utilizing the TRAIL pathway may be particularly effective for targeted OCCA therapy.
authors.affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shinjo
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Akatsuka
authors.forename: Nozomi
authors.initials: N
authors.lastname: Uno
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kamiya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Niimi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000401:mortality; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: C503627:CBX7 protein, human; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D063150:Polycomb Repressive Complex 1
keywords: TNFSF10 (TRAIL); chromobox homolog 7 (CBX7); expression microarray; immunohistochemistry; ovarian clear cell adenocarcinoma; siRNA