Predictive value of the ratio of 8‑hydroxydeoxyguanosine levels between cancerous and normal tissues in patients with stage II/III colorectal cancer

Kitagawa,Hiroshi; Kitajima,Yoshihiko; Kai,Keita; Komukai,Sho; Tanaka,Tomokazu; Koga,Yasuo; Manabe,Tatsuya; Noshirο,Hirokazu

doi:10.3892/or.2019.7086

Predictive value of the ratio of 8‑hydroxydeoxyguanosine levels between cancerous and normal tissues in patients with stage II/III colorectal cancer

Authors:
- Hiroshi Kitagawa
- Yoshihiko Kitajima
- Keita Kai
- Sho Komukai
- Tomokazu Tanaka
- Yasuo Koga
- Tatsuya Manabe
- Hirokazu Noshirο
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Affiliations: Department of Surgery, Saga University Faculty of Medicine, Saga 849‑8501, Japan, Department of Pathology, Saga University Hospital, Saga 849‑8501, Japan, Division of Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita‑City, Osaka 565‑0871, Japan
Published online on: March 22, 2019 https://doi.org/10.3892/or.2019.7086
Pages: 3041-3050

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Abstract

Reactive oxygen species (ROS) accumulation is known to induce carcinogenesis and accelerate cancer progression. 8‑Hydroxydeoxyguanosine (8‑OHdG) is a specific marker of ROS‑mediated DNA damage. Therefore, we analysed 8‑OHdG levels in cancerous and normal tissue DNA via enzyme‑linked immunosorbent assay (ELISA) using 97 tissue specimens obtained from surgically‑treated patients with stage II/III colorectal cancer (CRC). Additionally, 8‑OHdG levels in these tissues were also assessed via quantitative immunohistochemistry (qIHC). To eliminate individual background variables, the ratio of 8‑OHdG levels between cancerous and normal tissues was calculated using both techniques. A comparative analysis demonstrated that the 8‑OHdG ratio in DNA was significantly correlated with both lymph node metastasis and lymphatic invasion. Multivariate analysis revealed that a high 8‑OHdG ratio in DNA was independently correlated with poor prognosis. These results suggest that the 8‑OHdG ratio in DNA reflects ROS‑induced cancer progression. Conversely, a low 8‑OHdG ratio as estimated via qIHC was an independent factor for poor prognosis. In Kaplan‑Meier analysis, the combination of a high 8‑OHdG ratio in DNA (ELISA) and a low 8‑OHdG ratio in cytoplasm (qIHC) was associated with markedly worse patient prognosis than other combinations. Combined evaluation of the 8‑OHdG ratio using ELISA and qIHC may be pivotal for predicting surgical outcomes for patients with stage II/III CRC.

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