title: Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy.
abstract: DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients.
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ihara
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tani
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shida
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Domeki
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Kinro
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuchioka
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.affiliation: Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000076228:MRE11 Homologue Protein; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D051135:Rad51 Recombinase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D051135:Rad51 Recombinase; D000076228:MRE11 Homologue Protein