CXCR4 and RIF1 overexpression induces resistance of epithelial ovarian cancer to cisplatin-based chemotherapy

Abstract

Introduction: The chemoresistance of epithelial ovarian cancer (EOC) is a major problem. Thus, the search for novel biomarkers associated with cisplatin sensitivity is overwhelming. Previous studies have shown that CXC chemokine receptor 4 (CXCR4) is associated with tumor growth, angiogenesis, and distant metastases, and replication timing regulatory factor 1 (RIF1) is responsible for the repair of double-strand DNA breaks. This study, thus, aimed to identify the correlation between CXCR4 and RIF1 overexpression and cisplatin sensitivity in EOC. Materials and Methods: Fifty-five EOC patients were recruited to assess the chemosensitivity of EOC to cisplatin-based chemotherapy at the Oncology Department in Tanta University Hospitals, Egypt. Results: The results showed that patients with a higher CXCR4 and RIF1 expression exhibited a significantly lower chemosensitivity, worse overall survival, and poorer progression-free survival. The only prognostic associated with overall survival was CXCR4. Conclusion: Our study showed that CXCR4 and RIF1expression levels are not associated only with poor prognostic features of epithelial ovarian cancer but also with its chemoresistance to cisplatin, and consequently, with worse overall survival and progression free survival.

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

“… 2018 ; Sad et al. 2021 ). Similarly, genes downregulated in constant ph -KD tumors include known components required for DNA repair and replication fork protection in the presence of replication damage, such as the PCNA variant PCNA2 (Feng et al.…”

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

“…DNA repair genes over-expressed in constant ph -KD tumors include several components previously linked to damage accumulation, cancer formation, and/or poor cancer prognosis ( Table 1 ), like Mms4 ( Dewalt, Kesler et al 2014 ), RecQ4 ( Maire, Yoshimoto et al 2009 , Su, Meador et al 2010 , Xu, Chang et al 2021 ), PolH ( Tomicic, Aasland et al 2014 , Sonobe, Yang et al 2024 ), Tipin/Timeless ( Zhou, Zhang et al 2020 , Chen, Zhang et al 2022 ), Claspin ( Choi, Yang et al 2014 ), MRNIP ( Staples, Barone et al 2016 , Bennett, Wilkie et al 2020 , Wang, Zhao et al 2022 ), FANCI ( Smogorzewska, Matsuoka et al 2007 , Li, Yu et al 2023 ), MMR proteins (Msh2, Mlh1, Msh6) ( Shcherbakova and Kunkel 1999 , Velasco, Albert et al 2002 , Li, Liu et al 2008 , Wagner, Webber et al 2016 , Wilczak, Rashed et al 2017 , Chakraborty, Dinh and Alani 2018 , Donis, Gonzalez et al 2021 , Zhou, Xiao and Chen 2024 ), and Rif1 ( Liu, Mei et al 2018 , Mei, Liu et al 2018 , Sad, Mohamed et al 2021 ). Similarly, genes down regulated in constant ph -KD tumors include known components required for DNA repair and replication fork protection in the presence of replication damage, like the PCNA variant PCNA2 ( Feng, Xia et al 2023 ) ( Table 1 ).…”

The CXCR4 might be a potential biomarker for esophageal squamous cell carcinoma: A meta-analysis

“…While it usually expresses low or absent in normal tissues. [7][8][9] When CXCR4 binds to CXCL12, the CXCL12/CXCR4 axis is activated. The downstream signal pathways are activated, such as PI3k-Akt, Ras/Raf, NF-kB, MAPK, and so on, which influence the tumor occurrence, progress, and prognosis.…”