» Articles » PMID: 34296423

D-2-hydroxyglutarate Dehydrogenase in Breast Carcinoma As a Potent Prognostic Marker Associated with Proliferation

Overview
Date 2021 Jul 23
PMID 34296423
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

Background: D-2-hydroxyglutarate dehydrogenase (D2HGDH) catalyzes D-2-hydroxyglutarate to α-ketoglutarate and is involved in the regulation of cellular energy and biosynthetic intermediates. Previously, D2HGDH was reported to decrease 2-hydroxyglutarate level in breast carcinoma cells, but no other report has examined D2HGDH in breast carcinoma, and its significance remains unknown.

Methods: We first immunolocalized D2HGDH in 224 invasive breast carcinomas and evaluated its clinicopathological significance. We next examined associations between gene expression of D2HGDH and α-ketoglutarate-dependent dioxygenases in 23 breast carcinoma tissues using the gene expression profile data. Finally, we examined the effects of D2HGDH on the proliferation in three breast carcinoma cells.

Results: D2HGDH immunoreactivity was detected in 49% of invasive breast carcinomas, and the immunohistochemical D2HGDH status was positively associated with histological grade, HER2 and Ki-67, while it was inversely associated with estrogen receptor. Moreover, it was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both the disease-free and breast cancer-specific survival in these patients. Gene expression profile data revealed that D2HGDH expression was positively associated with the expression of 6 α-ketoglutarate-dependent dioxygenases (KDM3A, PLOD1, EGLN2, ALKBH1, ASPH and ALKBH7). Consequent in vitro experiments demonstrated that D2HGDH overexpression significantly increased the cell proliferation activity of MCF-7, T47D and MDA-MB-231 cells.

Conclusion: These results suggest that D2HGDH plays an important role in the growth of breast carcinoma, possibly through regulating functions of α-ketoglutarate-dependent dioxygenases, and that D2HGDH status is a potent worse prognostic factor in breast cancer patients.

Citing Articles

ALKBH1: emerging biomarker and therapeutic target for cancer treatment.

Xiao M, Fu J, Bo L, Li Y, Lin Z, Chen Z Discov Oncol. 2024; 15(1):816.

PMID: 39704856 PMC: 11662130. DOI: 10.1007/s12672-024-01696-5.


Regulation of Stromal Cells by Sex Steroid Hormones in the Breast Cancer Microenvironment.

Yamaguchi-Tanaka M, Takagi K, Sato A, Yamazaki Y, Miyashita M, Masamune A Cancers (Basel). 2024; 16(23).

PMID: 39682229 PMC: 11639972. DOI: 10.3390/cancers16234043.


Integrative pan-cancer analysis reveals the prognostic and immunotherapeutic value of ALKBH7 in HNSC.

Wang T, Lin B, Cai B, Cao Z, Liang C, Wu S Aging (Albany NY). 2024; 16(19):12781-12805.

PMID: 39400540 PMC: 11501379. DOI: 10.18632/aging.205981.


neomorphic mutation confers sensitivity to vitamin B12 in .

Ponomarova O, Starbard A, Belfi A, Anderson A, Sundaram M, Walhout A Life Sci Alliance. 2024; 7(10).

PMID: 39009411 PMC: 11249921. DOI: 10.26508/lsa.202402924.


Kallikrein-Related Peptidase 12 (KLK12) in Breast Cancer as a Favorable Prognostic Marker.

Sato A, Takagi K, Yoshimura A, Tsukamoto W, Yamaguchi-Tanaka M, Miki Y Int J Mol Sci. 2023; 24(9).

PMID: 37176127 PMC: 10179240. DOI: 10.3390/ijms24098419.


References
1.
Achouri Y, Noel G, Vertommen D, Rider M, Veiga-da-Cunha M, Van Schaftingen E . Identification of a dehydrogenase acting on D-2-hydroxyglutarate. Biochem J. 2004; 381(Pt 1):35-42. PMC: 1133759. DOI: 10.1042/BJ20031933. View

2.
Anderson N, Mucka P, Kern J, Feng H . The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell. 2017; 9(2):216-237. PMC: 5818369. DOI: 10.1007/s13238-017-0451-1. View

3.
Baksh S, Finley L . Metabolic Coordination of Cell Fate by α-Ketoglutarate-Dependent Dioxygenases. Trends Cell Biol. 2020; 31(1):24-36. PMC: 7748998. DOI: 10.1016/j.tcb.2020.09.010. View

4.
Chang W, Forde D, Lai A . Dual prognostic role of 2-oxoglutarate-dependent oxygenases in ten cancer types: implications for cell cycle regulation and cell adhesion maintenance. Cancer Commun (Lond). 2019; 39(1):23. PMC: 6489267. DOI: 10.1186/s40880-019-0369-5. View

5.
Chen M, Hsu L, Wang S, Hsu C, Lee H, Tseng L . ROS Mediate xCT-Dependent Cell Death in Human Breast Cancer Cells under Glucose Deprivation. Cells. 2020; 9(7). PMC: 7407809. DOI: 10.3390/cells9071598. View