Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer

Lü, Wei; Gao, Jian; Yang, Jingyun; Yang, Cao; Jiang, Lin; Li, Maolan; Zhang, Yijian; Zhou, Jian; Liu, Yingbin

doi:10.1097/md.0000000000002244

Cited by 13 publications

(8 citation statements)

References 36 publications

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“…Here, significant associations between high PGK1 expression and FIGO stage, histological grade, pathological type, and lymph node metastasis were identified. Similar to a report on gallbladder cancer [ 28 ], we further demonstrated that high PGK1 expression was associated with poor prognosis in endometrial carcinoma patients.…”

Section: Discussionsupporting

confidence: 90%

PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients

Guo

Xiao

et al. 2017

Oncotarget

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The aim of this study was to measure the expression patterns of PGK1 and GRP78 in normal endometrial tissues and endometrial carcinoma, and associations between their combined effects and the pathological features of endometrial carcinoma. We used 30 normal endometrial tissue samples and 130 endometrial carcinoma samples, and separately evaluated PGK1 and GRP78 protein expression by immunohistochemistry. Scores ranging from 0 to 9 were obtained by multiplying the percentage of positive cells by the staining intensity (0–3). Immunohistochemical analysis revealed increased PGK1 and GRP78 expression in the cytoplasm of endometrial carcinoma cells compared with that in normal endometrial tissues. High PGK1 expression positively correlated with the FIGO stage (P < 0.001), histological grade (P = 0.002), and lymph node status (P < 0.001). High GRP78 expression positively correlated with the pathological type (P = 0.0125), FIGO stage (P < 0.001), and lymph node status (P < 0.001). In addition, PGK1 overexpression was positively correlated with GRP78 overexpression in endometrial carcinoma patients (P < 0.001), and the concurrent expression of both oncogenes in endometrial carcinoma patients correlated significantly with the lymph node status (P < 0.001) and FIGO stage (P < 0.001). Patients with high PGK1 and GRP78 expression levels had poorer overall survival rates than those with low expression levels of both proteins (P < 0.001). Our results suggested that the co-occurrence of PGK1 and GRP78 expression is potentially an unfavorable factor for endometrial carcinoma progression.

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Section: Discussionsupporting

confidence: 90%

PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients

Guo

Xiao

et al. 2017

Oncotarget

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“…Hu et al ( 2017 ) found that PGK1 was overexpressed in liver cancer cells and that PGK1 acetylation promoted its enzyme activity and cancer cell metabolism. Additionally, PGK1 is also abnormally expressed in a great deal of cancers, such as gallbladder cancer (Lu et al, 2015 ), astrocytoma (Yan et al, 2012 ), gastric cancer (Zieker et al, 2010a , b ), and pancreatic ductal adenocarcinoma (Hwang et al, 2006 ), and it is closely correlated to tumor occurrence, metastasis, and invasion. Moreover, PKG1 can also be used as a target gene of miRNAs to modulate tumor development and progression.…”

Section: Discussionmentioning

confidence: 99%

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

et al. 2021

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Background: Glycolysis is critical in the occurrence and development of tumors. Owing to the biological and clinical heterogeneity of patients with BRCA, the traditional predictive classification system is far from satisfactory. Survival and prognosis biomarkers related to glycolysis have broad application prospects for assessing the risk of patients and guiding their individualized treatment.Methods: The mRNA expression profiles and clinical information of patients with BRCA were obtained from TCGA database, and glycolysis-related genes were obtained by GSEA. Patients with BRCA were randomly divided into the training cohort and testing cohort. Univariate and multivariate Cox analyses were used to establish and validate a new mRNA signature for predicting the prognosis of patients with BRCA.Results: We established a four-gene breast cancer prediction signature that included PGK1, SDHC, PFKL, and NUP43. The patients with BRCA in the training cohort and testing cohort were divided into high-risk and low-risk groups based on the signature. The AUC values were 0.74 (training cohort), 0.806 (testing cohort) and 0.769 (entire cohort), thereby showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that four-gene signature could independently predict the prognosis of BRCA patients without being affected by clinical factors.Conclusion: We constructed a four-gene signature to predict the prognosis of patients with BRCA. This signature will aid in the early diagnosis and personalized treatment of breast cancer, but the specific associated biological mechanism requires further study.

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“…PGK1 is a ubiquitous enzyme in all somatic cells and PGK2 is preferentially expressed in the testis 10 . Notably, PGK1, which is highly conserved from rabbits to humans and is a well-studied isozyme of the PGK family, has been reported to be upregulated in various types of tumor cells, such as colorectal cancer 11 , 12 , breast 4 , hepatocellular carcinoma 13 , gallbladder cancer 14 , and lung cancer. In addition, dysfunction of the PGK family involves metabolic programming and the Warburg effect in tumorigenesis 15 .…”

Section: Introductionmentioning

confidence: 99%

Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1

Chang

Chan

et al. 2021

Cell Death Discov.

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Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1.

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Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 13 publications

References 36 publications

PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients

PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

Metabolic protein phosphoglycerate kinase 1 confers lung cancer migration by directly binding HIV Tat specific factor 1

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