Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway.
Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway.
复制标题
DOI：
10.3390/ijms21176282
复制
发表时间：
2020-08-30
影响因子：
5.6
通讯作者：
Krzystek-Korpacka M
中科院分区：
文献类型：
--
作者：
Bednarz-Misa I;Fortuna P;Fleszar MG;Lewandowski Ł;Diakowska D;Rosińczuk J;Krzystek-Korpacka M
l -精氨酸/NO通路有望成为潜在治疗靶点和生物标志物的来源；然而，其在食管鳞状细胞癌（ESCC）中的地位和应用尚不清楚。我们的目的是使用LC-QTOF-MS定量ESCC （n = 61）和良性情况（n = 62）患者血清中的途径代谢物，使用实时荧光定量PCR参考ESCC病理和循环免疫/炎症介质，使用Luminex xMAP技术定量食管肿瘤和匹配的非癌样本（n = 40）中的酶表达。ESCC与全身精氨酸和不对称二甲基精氨酸升高有关。随着ESCC的进展，瓜氨酸的生物利用度降低，精氨酸的生物利用度增加。与邻近组织相比，肿瘤过表达ODC1、NOS2、PRMT1和PRMT5，而下调ARG1、ARG2和DDAH1。除了M1患者肿瘤中NOS2明显升高和ODC1明显降低外，病理相关的酶表达变化很微妙，在非癌组织中也存在。局部酶表达水平和全身代谢物浓度都与循环炎症和免疫介质有关，特别是与嗜酸性粒细胞和促进癌症干细胞活力和自我更新相关的介质。ESCC的代谢重编程表现为l -精氨酸/NO通路的改变。除了NOS2和ODC1外，PRMTs的上调以及与干细胞促进细胞因子相关的通路值得进一步研究。
The L-arginine/NO pathway holds promise as a source of potential therapy target and biomarker; yet, its status and utility in esophageal squamous cell carcinoma (ESCC) is unclear. We aimed at quantifying pathway metabolites in sera from patients with ESCC (n = 61) and benign conditions (n = 62) using LC-QTOF-MS and enzyme expression in esophageal tumors and matched noncancerous samples (n = 40) using real-time PCR with reference to ESCC pathology and circulating immune/inflammatory mediators, quantified using Luminex xMAP technology. ESCC was associated with elevated systemic arginine and asymmetric dimethylarginine. Citrulline decreased and arginine bioavailability increased along with increasing ESCC advancement. Compared to adjacent tissue, tumors overexpressed ODC1, NOS2, PRMT1, and PRMT5 but had downregulated ARG1, ARG2, and DDAH1. Except for markedly higher NOS2 and lower ODC1 in tumors from M1 patients, the pathology-associated changes in enzyme expression were subtle and present also in noncancerous tissue. Both the local enzyme expression level and systemic metabolite concentration were related to circulating inflammatory and immune mediators, particularly those associated with eosinophils and those promoting viability and self-renewal of cancer stem cells. Metabolic reprogramming in ESCC manifests itself by the altered L-arginine/NO pathway. Upregulation of PRMTs in addition to NOS2 and ODC1 and the pathway link with stemness-promoting cytokines warrants further investigation.
登录
查看更多内容
影响因子：
7.9
作者：
He W;Roh E;Yao K;Liu K;Meng X;Liu F;Wang P;Bode AM;Dong Z
通讯作者：
Dong Z
影响因子：
4.6
作者：
Di Franco M;Lucchino B;Conti F;Valesini G;Spinelli FR
通讯作者：
Spinelli FR
影响因子：
3.7
作者：
Chachaj A;Wiśniewski J;Rybka J;Butrym A;Biedroń M;Krzystek-Korpacka M;Fleszar MG;Karczewski M;Wróbel T;Mazur G;Gamian A;Szuba A
通讯作者：
Szuba A
影响因子：
0.9
作者：
Akoglu H
通讯作者：
Akoglu H
影响因子：
4.3
作者：
Keshet R;Erez A
通讯作者：
Erez A