High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer
Open accessAbstract
Tumors have exceptionally high demands for energy and anabolism because of their rapid growth. The de novo serine synthesis pathway initiated by phosphoglycerate dehydrogenase (PHGDH) has been recognized as a hallmark of metabolic adaption in carcinogenesis. The oncogenic role and prognostic value of PHGDH have been investigated in multiple cancer types, including breast cancer, melanoma, cervical cancer, and colon cancer. Due to the importance of PHGDH in cancer, we attempted to determine the clinical significance of PHGDH in 319 patients with non-small cell lung cancer (NSCLC). We evaluated the mRNA and protein expression levels of PHGDH gene, using quantitative reverse transcriptase polymerase chain reaction and tissue array-based immunohistochemistry, respectively. Significantly increased PHGDH expression in mRNA and protein levels was identified in tumor tissues versus matched adjacent nontumor tissues. More interestingly, immunohistochemical expression of PHGDH was significantly associated with lymph node metastasis (P=.021) and TNM stage (P=.016). Kaplan-Meier survival analysis indicated that NSCLC patients with low levels of PHGDH outperformed patients with high levels of PHGDH regarding 5-year overall survival. Significantly longer survival in the former suggested the prognostic implication of PHGDH in NSCLC. Multivariate survival analysis using Cox regression model demonstrated that high PHGDH levels and advanced TNM stage (III+IV) were independent predictors of prognosis in NSCLC. Moreover, bioinformatics analysis confirmed the increase in PHGDH transcripts (data from The Cancer Genome Atlas) and its prognostic value (Kaplan-Meier plotter) in NSCLC. In conclusion, this study suggested the clinical implication of PHGDH in NSCLC. PHGDH may be a promising therapeutic target in NSCLC.
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The up-regulation of glycolysis and one-carbon metabolism, and increased expression of corresponding enzymes, are usually observed in various neoplasms and are associated with metastasis, resistance to therapy, and poor prognosis.
“The up-regulation of glycolysis and one-carbon metabolism, and the increased expression of genes coding for corresponding enzymes, are usually observed in various neoplasms and are associated with metastasis, resistance to therapy, and poor prognosis.”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [68]
High expression of genes coding for these enzymes and their transcriptional regulators is strongly associated with shortened patient survival in different types of malignancies.
“The high expression of genes coding for all of these enzymes and their transcriptional regulators is strongly associated with a shortened patient survival in different types of malignancies [66,67,68,69,70,71,72,73,74].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [68]
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- Authors
- Zhu, J., Ma, J., Wang, X., Ma, T., Zhang, S., Wang, W., Zhou, X., & Shi, J.
- Affiliations
- Harbin Medical University (CN)
- Affiliated Hospital of Nantong University (CN)
- Corresponding author
- Zhou, Xiaoyu
- Shi, Jiahai
- Venue
- Translational Oncology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 9
- Issue
- 6
- Pages
- 592-599
- ISSN
- 1936-5233 (ISSN-L)
- PMC
- PMC5143353
- OpenAlex
- W2559083100
- Cited by
- 75
- References
- 36
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 5
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Translational Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Scientific Research Starting Foundation for Returned Overseas Chinese Scholars, Ministry of Education, China
- Six talent peaks project (WSW-049)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- PHGDH, non-small cell lung cancer, prognostic factors, serine biosynthesis, cancer metabolism, lymph node metastasis, TNM stage, overall survival, therapeutic target
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