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-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">SLC29A3 (ENT3) has been implicated in immune regulation and tumor biology; however, its pan-cancer prognostic relevance and role in hepatocellular carcinoma (HCC) remain unclear. </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">Materials and Methods: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">We performed comprehensive pan-cancer analyses using TCGA, GTEx, and CPTAC datasets to assess SLC29A3 mRNA and protein expression. Survival associations (OS, DSS, PFS, DFS) were evaluated using GEPIA2 and related survival tools. Promoter methylation status was examined via UALCAN. Tumor immune infiltration was analyzed using TIMER2.0 and correlated with immune cell subsets. Single-cell transcriptomic data from TISCH2 were used to characterize SLC29A3 expression within the HCC tumor microenvironment and to explore cell&ndash;cell communication patterns. Associations with immunotherapy response were investigated using publicly available immunotherapy cohorts. Drug sensitivity correlations were analyzed using the GDSC database. Radiotherapy response&ndash;related expression patterns were evaluated in relevant GEO datasets. A prognostic nomogram for early mortality in liver cancer was constructed using SEER data. Experimental validation was performed by RT-qPCR in paired HCC and adjacent normal tissues. </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="language:en-US">SLC29A3 was significantly overexpressed in multiple tumor types, including HCC, and its elevated expression correlated with poorer survival outcomes. Higher SLC29A3 levels were associated with increased immune infiltration, particularly macrophages and cancer-associated fibroblasts. Single-cell analysis localized SLC29A3 expression predominantly to CSF1R⁺CD14⁺ monocyte/macrophage populations. Drug sensitivity analysis suggested potential therapeutic implications. RT-qPCR confirmed upregulation in HCC tissues. </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="language:en-US">SLC29A3 is a potential prognostic biomarker linked to immune modulation and therapeutic response in HCC and multiple cancers.</span></span></span></span></span></span></span></span></span></div> SLC29A3, radiotherapy, Pan-cancer, Biomarker, Hepatocellular carcinoma. 953 960 http://ijrr.com/browse.php?a_code=A-10-1-1599&slc_lang=en&sid=1 Z. Yang 7900319475328460034563 7900319475328460034563 No The Second Clinical Medical School, Lanzhou University, Lanzhou, China W.  Zhu 7900319475328460034564 7900319475328460034564 No The Second Clinical Medical School, Lanzhou University, Lanzhou, China Y. Xu 7900319475328460034565 7900319475328460034565 No Shanghai Jiao Tong University School of Medicine, Shanghai, China T. Ma 7900319475328460034566 7900319475328460034566 No The Second Clinical Medical School, Lanzhou University, Lanzhou, China B. Tang 7900319475328460034567 7900319475328460034567 No Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner W.  Zhou zhouwc@lzu.edu.cn 7900319475328460034568 7900319475328460034568 Yes The Second Clinical Medical School, Lanzhou University, Lanzhou, China