Bioinformatic analysis of the role of solute carrier-glutamine transporters in breast cancer.
Bioinformatic analysis of the role of solute carrier-glutamine transporters in breast cancer.
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溶质载体-谷氨酰胺转运蛋白在乳腺癌中作用的生物信息学分析
DOI：
10.21037/atm-22-2620
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发表时间：
2022-07
影响因子：
--
通讯作者：
Liu, Qiang
中科院分区：
文献类型：
--
作者：
Zhao, Xin;Jin, Liang;Liu, Yujie;Liu, Zhenzhen;Liu, Qiang
背景乳腺癌是一种异质性很强的疾病。溶质载体(SLCs)参与了多种癌症类型的肿瘤进展。本研究旨在通过生物信息学分析评价SLC相关谷氨酰胺转运体在BC患者预后中的作用。方法本研究从目前世界上最大的癌基因微阵列数据库平台Oncomine数据库中检测BC中谷氨酰胺相关转运蛋白的转录和预后数据。以及基因表达谱交互分析(GEPIA)、Kaplan-Meier(K-M)和cBioPortal线上资源。采用肿瘤免疫评估资源(TIMER)和GEPIA检测SLCs与免疫细胞浸润的关系。结果乳腺癌组织中SLC1A5、SLC3A2、SLC7A5、SLC7A8和SLC38A1的表达水平高于正常乳腺组织，而SLC6A14的表达水平低于正常乳腺组织。SLC7A5、SLC7A8、SLC6A14和SLC38A2的表达水平与肿瘤的临床分期有关。K-M曲线显示SLC1A5高表达患者预后不良(OS HR=1.28，95%CI：1.06~1.54；P=0.01)。SLC3A2高表达与预后不良显著相关(DMFS HR=1.19，95%CI：1.02~1.39；P=0.027)。SLC7A5mRNA水平升高和SLC7A8mRNA水平降低与OS、RFS、DMFS和PPS的预后不良显著相关。SLC6A14高表达与预后不良显著相关(PPS HR=1.35，95%CI：1.07~1.7；P=0.011)。SLC38A1高表达与预后相关(RFS HR=0.84，95%CI：0.76~0.93；P=0.00077；DMFS HR=0.78，95%CI：0.67~0.91；P=0.0013)。免疫细胞及其标志基因的浸润与SLC1A5、SLC3A2、SLC7A5、SLC7A8、SLC6A14、SLC38A1、SLC38A2的表达有关。SLC7A5、SLC7A8、SLC38A1和SLC38A2具有调节肿瘤相关巨噬细胞极化的作用。结论SLC7A5、SLC7A8、SLC38A1和SLC38A2对肿瘤相关巨噬细胞的极化有调节作用。SLC1A5、SLC3A2、SLC7A5和SLC6A14可能是诊断BC的有前景的生物标志物，并可能成为这些患者潜在的治疗靶点。
Background Breast cancer (BC) is a highly heterogeneous disease. Solute carriers (SLCs) have been involved in the tumor progression of various cancer types. This study aimed to evaluate the role of these SLC-related glutamine transporters in the prognosis of BC patients by bioinformatics analysis. Methods This study examined the transcription and prognostic data for glutamine-related transporters in BC from Oncomine Database, which is currently the largest oncogene microarray database platform in the world. As well as Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier (K-M), and cBioPortal online resources. The Tumor Immune Estimation Resource (TIMER) and GEPIA were also used to examine the relationship between SLCs and immune cell infiltration. Results The expression levels of SLC1A5, SLC3A2, SLC7A5, SLC7A8, and SLC38A1 were higher in BC tissues than normal breast tissues, but the expression level of SLC6A14 was lower. The expression levels of SLC7A5, SLC7A8, SLC6A14, and SLC38A2 were related to a later clinical tumor stage. In the K-M analyses, The K-M curves revealed that patients with high SLC1A5 expression had a poor prognosis (OS HR =1.28, 95% CI: 1.06–1.54; P=0.01). The high expression of SLC3A2 was significantly correlated with a poor prognosis (DMFS HR =1.19, 95% CI: 1.02–1.39; P=0.027). Increased SLC7A5 mRNA levels and decreased SLC7A8 mRNA levels were significantly associated with a poor prognosis in terms of OS, RFS, DMFS and PPS. The high expression of SLC6A14 was significantly correlated with a poor prognosis (PPS HR =1.35, 95% CI: 1.07–1.7; P=0.011). The high expression of SLC38A1 was correlated with a better prognosis than low expression of SLC38A1 (RFS HR =0.84, 95% CI: 0.76–0.93; P=0.00077; DMFS HR =0.78, 95% CI: 0.67–0.91; P=0.0013). The infiltration of immune cells and their marker genes were associated with SLC1A5, SLC3A2, SLC7A5, SLC7A8, SLC6A14, SLC38A1, and SLC38A2 expression. SLC7A5, SLC7A8, SLC38A1, and SLC38A2 have the potential to regulate polarization in tumor-associated macrophages. Conclusions SLC7A5, SLC7A8, SLC38A1, and SLC38A2 may regulate the polarization of tumor-associated macrophages (TAMs). SLC1A5, SLC3A2, SLC7A5, and SLC6A14 may be promising biomarkers for the BC diagnosis and may represent potential therapeutic targets for these patients.
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影响因子：
8.8
作者：
Bacci, Marina;Lorito, Nicla;Morandi, Andrea
通讯作者：
Morandi, Andrea
DOI：
10.2174/156800805774912953
发表时间：
2005-12-01
期刊：
Current Drug Targets - Immune Endocrine and Metabolic Disorders
影响因子：
--
作者：
Ganapathy, M. E.;Ganapathy, V.
通讯作者：
Ganapathy, V.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
DOI：
10.1038/nrd4626
发表时间：
2015-08
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Lin L;Yee SW;Kim RB;Giacomini KM
通讯作者：
Giacomini KM
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS