Xia Tian, Zhang Qun-Xian, Liu Chang, Wang Ming-Liang, Miao Peng, Li Dan, Wei Li
Department of Thoracic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Clinical Medical School of Zhengzhou University, Zhengzhou, Henan Province, China.
Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
BMC Cancer. 2026 Jan 6;26(1):20. doi: 10.1186/s12885-025-15329-9.
SLC38A1 has been identified as a carcinogenic factor in the progression of colorectal, gastric, pancreatic, and other cancers. However, its involvement in lung adenocarcinoma (LUAD) remains unexplored in the literature.
The expression levels, diagnostic relevance, and clinical significance of SLC38A1 in LUAD were evaluated using data from the TCGA, XENA, and LCE databases, along with validation in samples from 10 LUAD patients at our hospital. Prognostic nomograms and risk models based on SLC38A1 were constructed. The functional roles and mechanisms of SLC38A1 in LUAD were investigated through CCK-8 assays, migration and invasion assays, Western blotting, GO and KEGG pathway analyses, and correlation analysis to explore its relationship with the immune microenvironment.
SLC38A1 was overexpressed in both unpaired and paired LUAD samples, with a marked increase in early-stage LUAD. Overexpression of SLC38A1 correlated with diagnostic accuracy and poor overall survival (HR = 1.53; 95% CI = 1.15-2.04), disease-free survival (HR = 1.59; 95% CI = 1.1-2.3), and progression-free interval (HR = 1.51; 95% CI = 1.16-1.97). COX regression analysis identified SLC38A1 overexpression as an independent risk factor for poor prognosis in LUAD patients. High-risk scores and nomograms associated with SLC38A1 were significantly linked to adverse clinical outcomes. Genes co-expressed with SLC38A1 were involved in nuclear division, DNA replication, and the cell cycle. Silencing of SLC38A1 expression inhibited LUAD cell growth and migration. Furthermore, SLC38A1 overexpression was associated with immune cell infiltration in LUAD, including Th2 cells, Tcm, T helper cells, and immune markers such as CD8A, CD8B, and CTLA4.
SLC38A1 is upregulated in LUAD, and its overexpression is associated with poor prognosis, diagnostic accuracy, and immune cell infiltration. SLC38A1-based risk models and nomograms offer potential predictive tools for assessing prognosis in LUAD patients.
SLC38A1已被确定为结直肠癌、胃癌、胰腺癌及其他癌症进展中的致癌因素。然而，其在肺腺癌（LUAD）中的作用在文献中尚未得到探索。
利用来自TCGA、XENA和LCE数据库的数据，评估SLC38A1在LUAD中的表达水平、诊断相关性和临床意义，并在我院10例LUAD患者的样本中进行验证。构建基于SLC38A1的预后列线图和风险模型。通过CCK-8试验、迁移和侵袭试验、蛋白质免疫印迹法、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析以及相关性分析，研究SLC38A1在LUAD中的功能作用和机制，以探索其与免疫微环境的关系。
SLC38A1在未配对和配对的LUAD样本中均过表达，在早期LUAD中显著升高。SLC38A1的过表达与诊断准确性及较差的总生存期（风险比[HR]=1.53；95%置信区间[CI]=1.15 - 2.04）、无病生存期（HR=1.59；95%CI=1.1 - 2.3）和无进展生存期（HR=1.51；95%CI=1.16 - 1.97）相关。COX回归分析确定SLC38A1过表达是LUAD患者预后不良的独立危险因素。与SLC38A1相关的高风险评分和列线图与不良临床结局显著相关。与SLC38A1共表达的基因参与核分裂、DNA复制和细胞周期。SLC38A1表达的沉默抑制了LUAD细胞的生长和迁移。此外，SLC38A1的过表达与LUAD中的免疫细胞浸润相关，包括Th2细胞、中央记忆T细胞（Tcm）、辅助性T细胞以及免疫标志物如CD8A、CD8B和细胞毒性T淋巴细胞相关抗原4（CTLA4）。
SLC38A1在LUAD中上调，其过表达与预后不良、诊断准确性及免疫细胞浸润相关。基于SLC38A1的风险模型和列线图为评估LUAD患者的预后提供了潜在的预测工具。
