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Comprehensive multi-omics analysis identifies SLC29A3 as a prognostic, immune, and radiotherapy response biomarker from pan-cancer to hepatocellular carcinoma
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Z. Yang   , W. Zhu , Y. Xu , T. Ma , B. Tang , W. Zhou |
| The Second Clinical Medical School, Lanzhou University, Lanzhou, China , zhouwc@lzu.edu.cn |
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Abstract: (16 Views) |
Background: 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. Materials and Methods: 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–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–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. Results: 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. Conclusion: SLC29A3 is a potential prognostic biomarker linked to immune modulation and therapeutic response in HCC and multiple cancers. |
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| Keywords: SLC29A3, radiotherapy, Pan-cancer, Biomarker, Hepatocellular carcinoma. |
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Full-Text [PDF 844 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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