<i>PHGDH</i> is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia

Zhong, Jiagui; Huang, Kezhi; Xie, Shaofan; Tan, Ailian; Peng, Jiaqin; Nie, Danian; Ma, Liping; Li, Yiqing

doi:10.7150/jca.90822

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J Cancer 2024; 15(9):2538-2548. doi:10.7150/jca.90822 This issue Cite

Research Paper

PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia

Jiagui Zhong^1,2,3*, Kezhi Huang^1,2,4*, Shaofan Xie^1,2, Ailian Tan^1,2, Jiaqin Peng^1,2, Danian Nie^1,2, Liping Ma^1,2✉, Yiqing Li^1,2✉

1. Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
3. Department of Hematology, The Affiliated Kashi Hospital, Sun Yat-sen University, Kashi 844099, China.
4. Internal Medicine Ward I, JieXi People's Hospital (Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University-JieXi Medical Center), JieYang 515499, China
^*JZ and KH contributed equally to this work.

Citation:

Zhong J, Huang K, Xie S, Tan A, Peng J, Nie D, Ma L, Li Y. PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia. J Cancer 2024; 15(9):2538-2548. doi:10.7150/jca.90822. https://www.jcancer.org/v15p2538.htm

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Abstract

As a rate-limiting enzyme for the serine biosynthesis pathway (SSP) in the initial step, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in many different tumors, and pharmacological or genetic inhibition of PHGDH promotes antitumor effects. In the present research, by analyzing several acute myeloid leukemia (AML) datasets in the Gene Expression Omnibus (GEO), we identified prognosis-related genes and constructed a multigene signature by univariate, multivariate Cox regression and LASSO regression. Subsequently, the multigene signature was confirmed through Cox, Kaplan-Meier, and ROC analyses in the validation cohort. Moreover, PHGDH acted as a risk factor and was correlated with inferior overall survival. We further analysed other datasets and found that PHGDH was overexpressed in AML. Importantly, the expression of PHGDH was higher in drug-resistant AML compared to drug-sensitive ones. In vitro experiments showed that inhibition of PHGDH induced apoptosis and reduced proliferation in AML cells, and these antitumor effects could be related to the Bcl-2/Bax signaling pathway by the noncanonical or nonmetabolic functions of PHGDH. In summary, we constructed a twenty-gene signature that could predicate prognosis of AML patients and found that PHGDH may be a potential target for AML treatment.

Keywords: Gene signature, Acute myeloid leukemia, Overall survival, PHGDH, Therapeutic target

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APA

Zhong, J., Huang, K., Xie, S., Tan, A., Peng, J., Nie, D., Ma, L., Li, Y. (2024). PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia. Journal of Cancer, 15(9), 2538-2548. https://doi.org/10.7150/jca.90822.

ACS

Zhong, J.; Huang, K.; Xie, S.; Tan, A.; Peng, J.; Nie, D.; Ma, L.; Li, Y. PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia. J. Cancer 2024, 15 (9), 2538-2548. DOI: 10.7150/jca.90822.

NLM

CSE

Zhong J, Huang K, Xie S, Tan A, Peng J, Nie D, Ma L, Li Y. 2024. PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia. J Cancer. 15(9):2538-2548.

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