Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic.
Department of Surgery I, Faculty of Medicine and Dentistry, University Hospital Olomouc, 779 00 Olomouc, Czech Republic.
Int J Mol Sci. 2023 May 17;24(10):8868. doi: 10.3390/ijms24108868.
DNA repair pathways are essential for maintaining genome stability, and understanding the regulation of these mechanisms may help in the design of new strategies for treatments, the prevention of platinum-based chemoresistance, and the prolongation of overall patient survival not only with respect to ovarian cancer. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) together with cytoreductive surgery (CRS) and adjuvant systemic chemotherapy is receiving more interest in ovarian cancer (OC) treatment because of the typical peritoneal spread of the disease. The aim of our study was to compare the expression level of 84 genes involved in the DNA repair pathway in tumors and the paired peritoneal metastasis tissue of patients treated with CRS/platinum-based HIPEC with respect to overall patient survival, presence of peritoneal carcinomatosis, treatment response, and alterations in the and genes. Tumors and metastatic tissue from 28 ovarian cancer patients collected during cytoreductive surgery before HIPEC with cisplatin were used for RNA isolation and subsequent cDNA synthesis. Quantitative real-time PCR followed. The most interesting findings of our study are undoubtedly the gene interactions among the genes , , , , , , and for primary tumor tissue and , , , , , , , and for metastases. Another interesting finding is the correlation between gene expression and overall survival (OS), where a low expression correlates with a worse OS.
DNA 修复途径对于维持基因组稳定性至关重要,了解这些机制的调控可能有助于设计新的治疗策略,预防铂类化疗耐药,并延长患者的总生存时间,不仅是针对卵巢癌。由于疾病的典型腹膜扩散,腹腔内热灌注化疗(HIPEC)联合细胞减灭术(CRS)和辅助全身化疗在卵巢癌(OC)治疗中受到更多关注。我们的研究目的是比较接受 CRS/基于铂类 HIPEC 治疗的患者的肿瘤和配对腹膜转移组织中 84 个参与 DNA 修复途径的基因的表达水平,与总患者生存、腹膜癌病的存在、治疗反应以及 和 基因的改变。在 HIPEC 顺铂治疗前的细胞减灭术中收集了 28 名卵巢癌患者的肿瘤和转移性组织,用于 RNA 分离和随后的 cDNA 合成。随后进行了定量实时 PCR。我们研究中最有趣的发现无疑是基因之间的相互作用,这些基因包括 、 、 、 、 、 、 ,对于原发肿瘤组织,以及 、 、 、 、 、 、 ,对于转移组织。另一个有趣的发现是基因表达与总生存(OS)之间的相关性,低表达与较差的 OS 相关。