T. Lai1, J. He2, H. Yang3, Z. Lei3, L. Zhou1, L. Zhang3, J. Yang3, J. Sui4, and Y. Z. Wu1; 1Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China, 2College of Bioengineering, Chongqing University, Chongqing, China, 3College of Medicine, Chongqing University, Chongqing, China, 4Department of Radiation Oncology, Chongqing Cancer Hospital & Cancer Institute, Chongqing, China
Purpose/Objective(s): Cancer-testis specific genes have been pursued as potential targets of anticancer therapy for more than 30 years. However, the mechanisms of these genes in tumor development and whether their reactivation plays roles in supporting tumorigenic features have not been thoroughly elucidated. Materials/
Methods: 277 CT-genes in CTdatabase were assessed for their expression status and potential prognostic value in lung adenocarcinoma using TCGA and GTEx data. Immunohistochemical staining was performed to investigate the expression of OIP5 in lung adenocarcinoma patients. To evaluate the radiosensitivity of cells, both in vitro and in vivo, colony formation assays and subcutaneous tumor transplantation models were utilized. The traffic light reporter system is used to assess the efficiency of homologous recombination and non-homologous end joining. Results: We identified 14 candidate CT-genes (TTK, CEP55, OIP5, CABYR, PRAME, ACRBP, LEMD1, XAGE1B, SPAG9, SPAG8, SPAG4, TMEM108, LY6K, and PBK) which are highly expressed in lung adenocarcinoma patients compared with non-tumoral tissues. However, subsequent analysis revealed that only OIP5 showed significant correlation with patient prognosis, and its expression was significantly upregulated in patients who received radiation therapy. The immunohistochemical results provided additional confirmation of the elevated expression of OIP5 in tumor tissues relative to normal tissues, and indicated an adverse prognosis for the patients. Colony formation and mouse models demonstrated that knocking down OIP5 significantly enhances the radiosensitivity of lung adenocarcinoma cells. The traffic light reporter system revealed that knocking down OIP5 significantly inhibits the efficiency of homologous recombination repair in cells. Conclusion: Collectively, our findings demonstrate that OIP5 may promote radioresistance in lung adenocarcinoma cells by facilitating homologous recombination repair, suggesting that OIP5 is a potential target for radiosensitization therapy.
