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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

Bioinformatic analysis of the role of solute carrier-glutamine transporters in breast cancer.

作者信息

Zhao Xin, Jin Liang, Liu Yujie, Liu Zhenzhen, Liu Qiang

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Ann Transl Med. 2022 Jul;10(14):777. doi: 10.21037/atm-22-2620.

DOI:10.21037/atm-22-2620
PMID:35965834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9372701/
Abstract

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 , and were higher in BC tissues than normal breast tissues, but the expression level of SLC6A14 was lower. The expression levels of , and were related to a later clinical tumor stage. In the K-M analyses, The K-M curves revealed that patients with high expression had a poor prognosis (OS HR =1.28, 95% CI: 1.06-1.54; P=0.01). The high expression of was significantly correlated with a poor prognosis (DMFS HR =1.19, 95% CI: 1.02-1.39; P=0.027). Increased mRNA levels and decreased mRNA levels were significantly associated with a poor prognosis in terms of OS, RFS, DMFS and PPS. The high expression of 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 (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 , and expression. , and have the potential to regulate polarization in tumor-associated macrophages.

CONCLUSIONS

, and may regulate the polarization of tumor-associated macrophages (TAMs). , and may be promising biomarkers for the BC diagnosis and may represent potential therapeutic targets for these patients.

摘要

背景

乳腺癌(BC)是一种高度异质性疾病。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估这些与SLC相关的谷氨酰胺转运蛋白在BC患者预后中的作用。

方法

本研究从Oncomine数据库(目前世界上最大的癌基因微阵列数据库平台)以及基因表达谱交互分析(GEPIA)、Kaplan-Meier(K-M)和cBioPortal在线资源中检查了BC中谷氨酰胺相关转运蛋白的转录和预后数据。肿瘤免疫估计资源(TIMER)和GEPIA也用于检查SLCs与免疫细胞浸润之间的关系。

结果

BC组织中、和的表达水平高于正常乳腺组织,但SLC6A14的表达水平较低。、和的表达水平与较晚的临床肿瘤分期相关。在K-M分析中,K-M曲线显示高表达患者预后较差(总生存期风险比[OS HR]=1.28,95%置信区间[CI]:1.06-1.54;P=0.01)。的高表达与较差的预后显著相关(远处转移无进展生存期风险比[DMFS HR]=1.19,95%CI:1.02-1.39;P=0.027)。就总生存期、无复发生存期、远处转移无进展生存期和无进展生存期而言,mRNA水平升高和mRNA水平降低与较差的预后显著相关。的高表达与较差的预后显著相关(无进展生存期风险比[PPS HR]=1.35,95%CI:1.07-1.7;P=0.011)。SLC38A1的高表达与低表达相比预后更好(无复发生存期风险比[RFS HR]=0.84,95%CI:0.76-0.93;P=0.00077;远处转移无进展生存期风险比[DMFS HR]=0.78,95%CI:0.67-0.91;P=0.0013)。免疫细胞及其标记基因的浸润与、和的表达相关。、和有可能调节肿瘤相关巨噬细胞的极化。

结论

、和可能调节肿瘤相关巨噬细胞(TAMs)的极化。、和可能是BC诊断中有前景的生物标志物,可能代表这些患者潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db1b/9372701/bfbf972fd3a2/atm-10-14-777-f7.jpg
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