谷氨酰胺代谢相关和氨基酸转运蛋白在肾上腺皮质肿瘤和嗜铬细胞瘤中的表达。

Expression of Glutamine Metabolism-Related and Amino Acid Transporter Proteins in Adrenal Cortical Neoplasms and Pheochromocytomas.

机构信息

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Dis Markers. 2021 Jan 5;2021:8850990. doi: 10.1155/2021/8850990. eCollection 2021.

DOI:10.1155/2021/8850990

PMID:33505538

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7806379/

Abstract

BACKGROUND

Glutamine metabolism is considered an important metabolic phenotype of proliferating tumor cells.

OBJECTIVE

The objective of this study was to investigate the expression of glutamine metabolism-related and amino acid transporter proteins in adrenal cortical neoplasms (ACNs) and pheochromocytomas (PCCs) in the adrenal gland.

METHODS

A tissue microarray was constructed for 132 cases of ACN (115 cases of adrenal cortical adenoma and 17 cases of adrenal cortical carcinoma) and 189 cases of PCC. Immunohistochemical staining for glutamine metabolism-related proteins GLS1 and GDH and amino acid transporter proteins SLC1A5, SLC7A5, and SLC7A11 as well as SDHB was performed and compared with clinicopathologic parameters.

RESULTS

The expression levels of GLS ( < 0.001), SLC7A5 ( = 0.049), and SDHB ( = 0.007) were higher in ACN than in PCC, whereas the expression levels of SLC1A5 ( < 0.001) and SLC7A11 ( < 0.001) were higher in PCC than in ACN. In ACN, GLS positivity was associated with a higher Fuhrman grade ( = 0.009), and SLC1A5 positivity was associated with SDHB positivity ( = 0.004) and a clear cell proportion < 25% ( = 0.010). SDHB negativity was also associated with tumor cell necrosis ( = 0.007). In PCC, SLC7A11 positivity was associated with nonnorepinephrine type ( = 0.008). In Kaplan-Meier analysis, patients with GLS positivity ( = 0.039) and SDHB negativity ( = 0.005) had significantly shorter overall survival in ACN. In PCC patients with a GAPP score ≥ 3, GLS positivity ( = 0.001) and SDHB positivity ( = 0.001) were associated with shorter disease-free survival, whereas GLS positivity ( = 0.004) was also associated with shorter overall survival.

CONCLUSIONS

The expression of glutamine metabolism-related and amino acid transporter proteins in ACN and PCC is distinct and associated with prognosis.

摘要

背景

谷氨酰胺代谢被认为是增殖性肿瘤细胞的重要代谢表型。

目的

本研究旨在探讨肾上腺皮质肿瘤（ACN）和嗜铬细胞瘤（PCC）中谷氨酰胺代谢相关蛋白和氨基酸转运蛋白的表达。

方法

构建了 132 例 ACN（115 例肾上腺皮质腺瘤和 17 例肾上腺皮质癌）和 189 例 PCC 的组织微阵列。对谷氨酰胺代谢相关蛋白 GLS1 和 GDH 以及氨基酸转运蛋白 SLC1A5、SLC7A5 和 SLC7A11 以及 SDHB 进行免疫组织化学染色，并与临床病理参数进行比较。

结果

与 PCC 相比，ACN 中 GLS（<0.001）、SLC7A5（=0.049）和 SDHB（=0.007）的表达水平更高，而 SLC1A5（<0.001）和 SLC7A11（<0.001）的表达水平更高。在 ACN 中，GLS 阳性与 Fuhrman 分级较高（=0.009）相关，SLC1A5 阳性与 SDHB 阳性（=0.004）和透明细胞比例<25%（=0.010）相关。SDHB 阴性也与肿瘤细胞坏死有关（=0.007）。在 PCC 中，SLC7A11 阳性与非去甲肾上腺素型有关（=0.008）。在 Kaplan-Meier 分析中，ACN 中 GLS 阳性（=0.039）和 SDHB 阴性（=0.005）的患者总生存时间显著缩短。在 GAPP 评分≥3 的 PCC 患者中，GLS 阳性（=0.001）和 SDHB 阳性（=0.001）与无病生存期较短相关，而 GLS 阳性（=0.004）也与总生存期较短相关。