en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background:</span></span></span></span></span></span> <span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">Folate metabolism is essential in cancer progression and therapeutic response by supporting DNA synthesis, repair, and methylation. However, the differential impact of systemic folate (RBC Folate) versus local folate (Follicular Fluid Folate, FFF) on radiotherapy outcomes in cancer patients remains unclear. </span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-GB">Materials and Methods: </span></span></span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">A cross-sectional study was conducted on 280 female patients with reproductive tract cancers undergoing pelvic radiotherapy. Blood and follicular fluid samples were collected before radiotherapy. RBC Folate and FFF concentrations were quantified. Radiotherapy outcomes-including tumor shrinkage (assessed via imaging), DNA damage repair (</span></span></span></span><span lang="el" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:el">&gamma;-</span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">H2AX assay), and clinical treatment response-were analyzed using Pearson correlation and multiple linear regression. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">Higher FFF levels were significantly associated with enhanced DNA repair and increased tumor persistence (</span></span></span></span><span lang="el" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:el">&beta; = 0.02171, </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">P = 0.0363), indicating a potential protective effect on tumor cells. Conversely, elevated RBC Folate was negatively correlated with radiotherapy response (</span></span></span></span><span lang="el" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:el">&beta; = -0.002011, </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">P = 0.0015). Tumor shrinkage and DNA repair parameters were the strongest predictors of treatment success. Age and tumor type also influenced the outcomes negatively. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">Local and systemic folate levels exhibit opposing effects on radiotherapy response in gynecological cancer patients. Elevated FFF may enhance tumor resilience, whereas higher RBC Folate may reduce treatment efficacy. Folate profiling could guide personalized strategies to optimize radiotherapy outcomes.</span></span></span></span></span></span></span></span></span></span></div> Neoplasms, radiotherapy. folate, red blood cell count, follicular fluid, DNA repair, tumor microenvironment. 159 165 http://ijrr.com/browse.php?a_code=A-10-1-1470&slc_lang=en&sid=1 T. Huang AmonUhn8286@hotmail.com 7900319475328460033058 7900319475328460033058 Yes The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China