title: Individual and Combined Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predict Shorter Survival of Soft Tissue Sarcoma Patients.
abstract: DNA damage response (DDR) molecules are protective against genotoxic stresses. DDR molecules are also involved in the survival of cancer cells in patients undergoing anti-cancer therapies. Therefore, DDR molecules are potential markers of cancer progression in addition to being potential therapeutic targets. In this study, we evaluated the immunohistochemical expression of PARP1, γH2AX, BRCA1, and BRCA2 and their prognostic significance in 112 cases of soft tissue sarcoma (STS). The expression of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with each other and were associated with higher tumor stage and presence of distant metastasis. The expression of PARP1, γH2AX, and BRCA2 were significantly associated with shorter disease-specific survival (DSS) and event-free survival (EFS) by univariate analysis. BRCA1 expression was associated with shorter DSS. Multivariate analysis revealed the expression of PARP1 and γH2AX to be independent indicators of poor prognosis of DSS and EFS. BRCA2 expression was an independent indicator of poor prognosis of DSS. In addition, the combined expressional patterns of PARP1, γH2AX, BRCA1, and BRCA2 (CSddrm) were independent prognostic predictors of DSS (P < 0.001) and EFS (P = 0.016). The ten-year DSS rate of the CSddrm-low, CSddrm-intermediate, and CSddrm-high subgroups were 81%, 26%, and 0%, respectively. In conclusion, this study demonstrates that the individual and combined expression patterns of the DDR molecules PARP1, γH2AX, BRCA1, and BRCA2 could be predictive of the prognosis of STS patients and suggests that controlling the activity of these DDR molecules could be employed in new therapeutic stratagems for the treatment of STS.
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Moon
authors.affiliation: Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea.
authors.forename: See-Hyoung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Wang
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Dong Geun
authors.initials: DG
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Jung Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D004249:DNA Damage; D006657:Histones / Q000235:genetics*; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C468783:H2AX protein, human; D006657:Histones; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1