Du Wenxing, Zang Bo, Wo Yang, Chen Shiwei
Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Department of Rheumatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Biochem Biophys Rep. 2025 Apr 28;42:102034. doi: 10.1016/j.bbrep.2025.102034. eCollection 2025 Jun.
SLC16A3, a highly expressed H + -coupled symporter, facilitates lactate transport via monocarboxylate transporters (MCTs), contributing to acidosis. Although SLC16A3 has been implicated in tumor development, its role in tumor immunity remains unclear.
A pan-cancer analysis was conducted using datasets from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, and Genotype-Tissue Expression projects. SLC16A3 expression patterns and associations with tumor progression, prognosis, immune checkpoints, and immune neoantigens were evaluated across 30 cancer types. Immune infiltration scores were analyzed using the Tumor Immune Estimation Resource dataset.
SLC16A3 expression is differentially regulated in cancer versus healthy tissues, with elevated levels associated with poor prognosis and reduced overall survival in glioblastoma multiforme (HR = 1.88), low-grade gliomas (HR = 1.51), and lung adenocarcinoma (HR = 1.33). Notably, significant associations between SLC16A3 expression and poor outcomes were observed in 33 cancers, except for rectum adenocarcinoma, testicular germ cell tumors, pheochromocytoma and paraganglioma, and adrenocortical carcinoma. SLC16A3 expression was also strongly linked to immune checkpoints and neoantigens. Correlations with tumor-infiltrating immune cells were pronounced in prostate adenocarcinoma but absent in uterine carcinosarcoma and cervical squamous cell carcinoma. Gene set enrichment analysis (GSEA) revealed a pivotal role of SLC16A3 in tumor growth, metabolism, and immunity.
SLC16A3, the transporter facilitating the efflux of lactic acid, shows differential expression across various cancer types and exerts a critical effect on tumor development and immunity. Thus, SLC16A3 has promising potential as a prognostic marker, and its targeted manipulation can offer therapeutic advantages.
SLC16A3是一种高表达的H⁺偶联同向转运体，通过单羧酸转运体（MCTs）促进乳酸转运，导致酸中毒。尽管SLC16A3与肿瘤发展有关，但其在肿瘤免疫中的作用仍不清楚。
使用来自癌症基因组图谱、癌细胞系百科全书和基因型-组织表达项目的数据集进行泛癌分析。评估了SLC16A3在30种癌症类型中的表达模式及其与肿瘤进展、预后、免疫检查点和免疫新抗原的关联。使用肿瘤免疫估计资源数据集分析免疫浸润评分。
SLC16A3在癌组织与健康组织中的表达受到不同调节，其水平升高与多形性胶质母细胞瘤（HR = 1.88）、低级别胶质瘤（HR = 1.51）和肺腺癌（HR = 1.33）的预后不良和总生存期缩短相关。值得注意的是，除直肠腺癌、睾丸生殖细胞肿瘤、嗜铬细胞瘤和副神经节瘤以及肾上腺皮质癌外，在33种癌症中观察到SLC16A3表达与不良预后之间存在显著关联。SLC16A3表达还与免疫检查点和新抗原密切相关。在前列腺腺癌中与肿瘤浸润免疫细胞的相关性显著，但在子宫癌肉瘤和宫颈鳞状细胞癌中不存在。基因集富集分析（GSEA）揭示了SLC16A3在肿瘤生长、代谢和免疫中的关键作用。
促进乳酸外流的转运体SLC16A3在各种癌症类型中表现出差异表达，并对肿瘤发展和免疫发挥关键作用。因此，SLC16A3作为一种预后标志物具有广阔的潜力，对其进行靶向调控可带来治疗优势。
