溶质载体家族7成员1在泛癌中的预后及免疫价值研究-现代医学

溶质载体家族7成员1在泛癌中的预后及免疫价值研究

单位：1. 福建医科大学福总临床医学院妇产科, 福建福州 350025;
2. 厦门大学附属东方医院妇产科, 福建福州 350025

分类号：R730.7

出版年·卷·期（页码）：2025·53·第九期（1379-1389）

摘要：

目的： 运用生物信息学方法探讨溶质载体家族7基因1在泛癌中的表达、预后意义及潜在发病机制。方法： 从癌症基因组图谱(TCGA)数据库、基因型-组织表达(GTEx)数据库和TIMER 2.0数据库中分别下载泛癌、正常组织的DNA甲基化谱和表型数据以及33种癌症中免疫细胞浸润数据。使用 “plotly”和“ggpubr” R包对SLC7A1基因表达数据进行可视化，并计算不同类型肿瘤和正常样本的表达差异，通过t检验评估其统计显著性；采用Cox回归分析SLC7A1表达与患者预后之间的关联；采用Spearman相关性分析SLC7A1基因表达数据与免疫细胞浸润之间的关系，并计算各免疫检查点与特定基因表达值之间的相关性。结果： 与正常组织相比，SLC7A1在多种肿瘤中表达差异有统计学意义(P<0.05)，且其表达水平与患者预后密切相关。通过基因突变分析显示，SLC7A1在泛癌中的基因变异类型主要为拷贝缺失。免疫相关性分析显示，SLC7A1与多种癌症类型中多种类型免疫细胞的浸润呈负相关，且在葡萄膜黑色素瘤、嗜铬细胞瘤、卵巢癌、肝癌、乳腺癌和膀胱尿路上皮癌中观察到SLC7A1与免疫检查点表达呈正相关。此外，在多数肿瘤类型中，SLC7A1 mRNA表达与拷贝数变异之间也存在显著正相关，其中前3种最相关的肿瘤分别是直肠癌、结肠癌和胃癌。结论： SLC7A1在多种肿瘤中表达上调，且与预后不良密切相关，同时SLC7A1表达与肿瘤微环境免疫浸润有关，是潜在的肿瘤治疗的新靶点。

Objective: To investigate the expression, prognostic significance, and potential pathogenic mechanisms of solute carrier family 7 member 1(SLC7A1) in pan-cancer using bioinformatics methods. Methods: DNA methylation profiles, phenotypic data of pan-cancer and normal tissues, and immune cell infiltration data across 33 types of cancers were downloaded from The Cancer Genome Atlas(TCGA) database, Genotype-Tissue Expression(GTEx) database, and TIMER 2.0 database, respectively. The “plotly” and “ggpubr” R packages were used to visualize SLC7A1 gene expression data, calculate the expression differences between different tumor and normal samples, and assess statistical significance via t-test. Cox regression analysis was performed to explore the association between SLC7A1 expression and patient prognosis. Spearman correlation analysis was used to analyze the relationship between SLC7A1 expression and immune cell infiltration, as well as the correlation between various immune checkpoints and the expression levels of specific genes. Results: Compared with normal tissues, SLC7A1 showed statistically significant differences in expression in multiple tumors(P<0.05), and its expression level was closely associated with patient prognosis. Genetic mutation analysis revealed that the main type of genetic variation of SLC7A1 in pan-cancer was copy number deletion. Immune correlation analysis indicated that SLC7A1 was negatively correlated with the infiltration of various immune cell types in multiple cancer types. Moreover, positive correlations between SLC7A1 and immune checkpoint expression were observed in uveal melanoma, pheochromocytoma, ovarian cancer, liver cancer, breast cancer, and bladder urothelial carcinoma. In addition, a significant positive correlation between SLC7A1 mRNA expression and copy number variation was found in most tumor types, with the top 3 most relevant tumors being rectal cancer, colon cancer, and gastric cancer. Conclusion: SLC7A1 is upregulated in multiple tumors and closely associated with poor prognosis. Meanwhile, SLC7A1 expression is related to immune infiltration in the tumor microenvironment, suggesting that it may serve as a potential novel target for tumor therapy.

参考文献：

[1] BRAY F,LAVERSANNE M,WEIDERPASS E,et al.The ever-increasing importance of cancer as a leading cause of premature death worldwide[J].Cancer,2021,127(16):3029-3030.
[2] 李乐佳,宋冬.以肿瘤相关巨噬细胞为靶点的结直肠癌治疗机制的研究进展[J].现代医学,2024,52(4):658-662.
[3] AKTER S,RAHMAN M A,HASAN M N,et al.Recent advances in ovarian cancer:therapeutic strategies,potential biomarkers,and technological improvements[J].Cells,2022,11(4):650.
[4] JIN J,KIM C,XIA Q,et al.Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals[J].Sci Immunol,2021,6(60):eabg0791.
[5] HÖGLUND P J,NORDSTRÖM K J V,SCHIÖTH H B,et al.The solute carrier families have a remarkably long evolutionary history with the majority of the human families present before divergence of Bilaterian species[J].Mol Biol Evol,2011,28(4):1531-1541.
[6] YOU S,ZHU X,YANG Y,et al.SLC7A1 overexpression is involved in energy metabolism reprogramming to induce tumor progression in epithelial ovarian cancer and is associated with immune-infiltrating cells[J].J Oncol,2022,2022:5864826.
[7] YOU S,HAN X,XU Y,et al.High expression of SLC7A1 in high-grade serous ovarian cancer promotes tumor progression and is involved in MAPK/ERK pathway and EMT[J].Cancer Med,2024,13(10):e7217.
[8] YAN L,HE J,LIAO X,et al.A comprehensive analysis of the diagnostic and prognostic value associated with the SLC7A family members in breast cancer[J].Gland Surg,2022,11(2):389-411.
[9] CHAGOVETS V,STARODUBTSEVA N,TOKAREVA A,et al.Specific changes in amino acid profiles in monocytes of patients with breast,lung,colorectal and ovarian cancers[J].Front Immunol,2024,14:1332043.
[10] LU Y,WANG W,WANG J,et al.Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue[J].PLoS One,2013,8(9):e73866.
[11] GAI X,LIU Y,LAN X,et al.Oncogenic KRAS induces arginine auxotrophy and confers a therapeutic vulnerability to SLC7A1 inhibition in non-small cell lung cancer[J].Cancer Res,2024,84(12):1963-1977.
[12] WANG W,ZOU W.Amino acids and their transporters in T cell immunity and cancer therapy[J].Mol Cell,2020,80(3):384-395.
[13] QUARESIMA B,SCICCHITANO S,FANIELLO M C,et al.Role of solute carrier transporters in ovarian cancer(Review)[J].Int J Mol Med,2025,55(2):24.
[14] JÄGER K,BÖNISCH U,RISCH M,et al.Detection and regulation of cationic amino acid transporters in healthy and diseased ocular surface[J].Invest Ophthalmol Vis Sci,2009,50(3):1112-1121.
[15] YOU S,HAN X,XU Y,et al.Research progress on the role of cationic amino acid transporter(CAT) family members in malignant tumors and immune microenvironment[J].Amino Acids,2023,55(10):1213-1222.
[16] XU J,FANG Y,CHEN K,et al.Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer[J].Clin Cancer Res,2022,28(16):3590-3602.
[17] HE W,ZHANG J,LIU B,et al.S119N mutation of the E3 ubiquitin ligase SPOP suppresses SLC7A1 degradation to regulate hepatoblastoma progression[J].Mol Ther Oncolytics,2020,19:149-162.
[18] SAGHAFINIA S,MINA M,RIGGI N,et al.Pan-cancer landscape of aberrant DNA methylation across human tumors[J].Cell Rep,2018,25(4):1066-1080.e8.
[19] KOCH A,JOOSTEN S C,FENG Z,et al.Analysis of DNA methylation in cancer:location revisited[J].Nat Rev Clin Oncol,2018,15(7):459-466.
[20] WU Z,ZHUANG X,LIANG M,et al.Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer[J].Front Mol Biosci,2024,11:1394902.
[21] NISHIYAMA A,NAKANISHI M.Navigating the DNA methylation landscape of cancer[J].Trends Genet,2021,37(11):1012-1027.
[22] BECHT E,GIRALDO N A,DIEU-NOSJEAN M C,et al.Cancer immune contexture and immunotherapy[J].Curr Opin Immunol,2016,39:7-13.
[23] MCCARTHY E F.The toxins of William B.Coley and the treatment of bone and soft-tissue sarcomas[J].Iowa Orthop J,2006,26:154-158.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录