ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming

Mishra, Prachi; Tang, Wei; Putluri, Vasanta; Dorsey, Tiffany H.; Jin, Feng; Wang, Fang; Zhu, Donewei; Amable, Lauren; Deng, Tao; Zhang, Shaofei; Killian, J. Keith; Wang, Yonghong; Minas, Tsion Z.; Yfantis, Harry G.; Lee, Dong Hoon; Sreekumar, Arun; Bustin, Michael; Liu, Wei; Putluri, Nagireddy; Ambs, Stefan

doi:10.1172/jci93815

Cited by 64 publications

(56 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Metabolic extraction was performed as described previously. 12,13,[24][25][26] Briefly, serum samples were stored at -80°C until the analysis. Serum (40 µL) was used for metabolite extraction; the serum pool was used as a quality control.…”

Section: Sample Preparation For Ms and Metabolomic Analysismentioning

confidence: 99%

“…[11][12][13] As markers, metabolites could be used to improve individual risk prediction in BLCA. [11][12][13] As markers, metabolites could be used to improve individual risk prediction in BLCA.…”

Section: Introductionmentioning

confidence: 99%

“…Metabolomic studies have now begun to identify disease-specific metabolic signatures and correlate them with clinical outcomes. [11][12][13] As markers, metabolites could be used to improve individual risk prediction in BLCA. Mass spectrometry (MS), in combination with various liquid chromatography methods, has been previously applied to study BLCA-induced metabolomic alterations in tissues, 11,14-17 urine, [18][19][20][21] and serum.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND: African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS: Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS: Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS: This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities. Cancer 2019;125:921-932.

show abstract

Section: Sample Preparation For Ms and Metabolomic Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Vantaku

Donepudi

Piyarathna

et al. 2019

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…RASSF4 is a member of the RASSF family of tumor suppressors. AOC4P is a lncRNA involved in Hepatocellular Carcinoma and Colorectal Cancer [22] and ADHFE1 is a breast cancer oncogene [41].…”

Section: Resultsmentioning

confidence: 99%

Finding associations in a heterogeneous setting: Statistical test for aberration enrichment

Mezlini

Das

Goldenberg

2020

Preprint

View full text Add to dashboard Cite

Most two-group statistical tests are implicitly looking for a broad pattern such as an overall shift in mean, median or variance between the two groups. Therefore, they operate best in settings where the effect of interest is uniformly affecting everyone in one group versus the other. In real-world applications, there are many scenarios where the effect of interest is heterogeneous. For example, a drug that works very well on only a proportion of patients and is equivalent to a placebo on the remaining patients, or a disease associated gene expression dysregulation that only occurs in a proportion of cases whereas the remaining cases have expression levels indistinguishable from the controls for the considered gene. In these examples with heterogeneous effect, we believe that using classical two-group statistical tests may not be the most powerful way to detect the signal. In this paper, we developed a statistical test targeting heterogeneous effects and demonstrated its power in a controlled simulation setting compared to existing methods. We focused on the problem of finding meaningful associations in complex genetic diseases using omics data such as gene expression, miRNA expression, and DNA methylation. In simulated and real data, we showed that our test is complementary to the traditionally used statistical tests and is able to detect disease-relevant genes with heterogeneous effects which would not be detectable with previous approaches.

show abstract

“…was associated with good survival and down-regulated in advanced stages. ADHFE1 was reported as an oncogene by inducing metabolic reprogramming in breast cancer 56 , but no previous association with gastric cancer was reported. Interestingly, Oh et al also observed upregulation of IGF1 coupled with promoter region hypomethylation in mesenchymal gastric tumors and showed inhibition of IGF1 reduced tumor growth in mesenchymal type tumor cells 46 .…”

Section: Discussionmentioning

confidence: 99%

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Yoo

Chen

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Gastric cancer (GC) is a heterogeneous disease of diverse genetic, genomic, and epigenetic alterations. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate GC heterogeneity, we developed an Integrative Sequential Causality Test (ISCT) to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts containing methylation, CNV and transcriptomic data, 11 common methylation-driven key regulators (ADHFE1, CDO1, CRYAB, FSTL1, GPT, PKP3, PTPRCAP, RAB25, RHOH, SFN, and SORD) were identified. Based on these 11 genes, gastric tumors were clustered into 3 clusters which were associated with known molecular subtypes, Lauren classification, tumor stage, and patient survival, suggesting significance of the methylation-driven key regulators in molecular and histological heterogeneity of GC. We further showed that chemotherapy benefit was different in the 3 GC clusters and varied depending on the tumor stage. Both immune/stromal proportions in TME and tumor cell genomic variations contributed to expression variations of the 11 methylation-driven key regulators and to the GC heterogeneity.

show abstract

ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming

Cited by 64 publications

References 57 publications

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Large‐scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival

Finding associations in a heterogeneous setting: Statistical test for aberration enrichment

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Contact Info

Product

Resources

About