Differential roles of the Wip1-p38-p53 DNA damage response pathway in early/advanced-stage ovarian clear cell carcinomas

• Published in: World journal of surgical oncology 2022-04, Vol.20 (1), p.139-139, Article 139
• Main Authors: Xu, Chenyang, Minaguchi, Takeo, Qi, Nan, Fujieda, Kaoru, Suto, Asami, Itagaki, Hiroya, Shikama, Ayumi, Tasaka, Nobutaka, Akiyama, Azusa, Nakao, Sari, Ochi, Hiroyuki, Satoh, Toyomi
• Format: Article
• Language: English
• Subjects: Advanced stage; Apoptosis; Cancer; Carcinoma; Cell cycle; Cellular biology; Chemoresistance; Chemotherapy; Correlation; Damage; Deoxyribonucleic acid; Disease; DNA; DNA Damage; DNA repair; Drug therapy; Genetic aspects; Health aspects; Histology; Humans; Immunohistochemistry; Lymphatic system; Medical prognosis; Metastasis; Methods; Oncology, Experimental; Ovarian cancer; Ovarian carcinoma; Ovarian clear cell carcinoma; p53 Protein; Patients; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Prognosis; Protein Phosphatase 2C - genetics; Protein Phosphatase 2C - metabolism; Proteins; Survival; Therapeutic targets; Trends; Tumor Suppressor Protein p53 - metabolism; Wip1
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-022-02600-7

Ovarian clear cell carcinoma (OCCC) is one of the most lethal types of ovarian cancer. Early-stage OCCC can be cured by surgery; however, advanced-stage disease shows poor prognosis due to chemoresistance unlike the more common high-grade serous carcinoma. We explored the differential roles of the Wip1-p38-p53 DNA damage response pathway in respective early- or advanced-stage OCCC by immunohistochemistry of Wip1, phospho-p38, p53, and phospho-p53 from consecutive 143 patients. High Wip1 expression correlated with positive p53 (p=0.011), which in turn correlated with low nuclear phospho-p38 expression (p=0.0094). In the early stages, positive p53 showed trends toward worse overall survival (OS) (p=0.062), whereas in the advanced stages, high Wip1 correlated with worse OS (p=0.0012). The univariate and multivariate analyses of prognostic factors indicated that high Wip1 was significant and independent for worse OS (p=0.011) in the advanced stages, but not in the early stages. Additionally, high Wip1 showed trends toward shorter treatment-free interval (TFI) in the advanced stages, but not in the early stages (p=0.083 vs. 0.93). Furthermore, high Wip1 was significantly associated with positive p53 only in the patients with shorter TFI (