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BIOMARKER:

GDF15 overexpression

i
Other names: GDF15, MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB, Growth differentiation factor 15
Entrez ID:
Related biomarkers:
1m
GDF15 induces chemoresistance to oxaliplatin by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis in colorectal cancer. (PubMed, Cell Oncol (Dordr))
This study identified a novel GDF15-Nrf2 positive feedback loop that drives L-OHP resistance and suggested that the GDF15-Nrf2 axis is a potential therapeutic target for the treatment of L-OHP-resistant CRC.
Journal
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GDF15 (Growth differentiation factor 15)
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GDF15 overexpression
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oxaliplatin
3ms
Overexpression of Growth Differentiation Factor 15 in Glioblastoma Stem Cells Promotes Their Radioresistance. (PubMed, Cancers (Basel))
In addition, we also found that GDF15 expression is critical for GSC spheroid formation, as GDF15 knockdown significantly reduces the number of GSC neurospheres. This study suggests that GDF15 targeting in combination with radiotherapy may be a feasible approach in patients with GBM.
Journal
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GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1) • WWTR1 (WW Domain Containing Transcription Regulator 1)
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GDF15 overexpression
3ms
GDF-15 alleviates diabetic nephropathy via inhibiting NEDD4L-mediated IKK/NF-κB signalling pathways. (PubMed, Int Immunopharmacol)
Taken together, our data suggested a protective mechanism of elevated GDF-15 in DN through obstruction of ubiquitin degradation of IKK by inhibiting NEDD4L expression, thus decreasing the activation of NF-κB and relieving the inflammation. GDF-15 could serve as a potential therapeutic target for DN.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • GDF15 (Growth differentiation factor 15) • IL1B (Interleukin 1, beta) • NFKBIA (NFKB Inhibitor Alpha 2)
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GDF15 elevation • GDF15 overexpression
4ms
Downregulation of GDF15 suppresses ferroptosis and predicts unfavorable prognosis in clear cell renal cell carcinoma. (PubMed, Cell Div)
Our study demonstrates that GDF15 downexpression promotes viability and aggressiveness of ccRCC cells by abolishing ferroptosis, which confers unfavorable patient survival outcomes.
Journal
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GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1)
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GDF15 overexpression
5ms
Erythroid differentiation enhances RNA mis-splicing in SF3B1-mutant myelodysplastic syndromes with ring sideroblasts. (PubMed, Cancer Res)
Finally, RNA mis-splicing induced an uncoupling of RNA and protein expression, leading to critical abnormalities in proapoptotic p53 pathway genes. Overall, this characterization of erythropoiesis in SF3B1mt RS provides a resource for studying MDS-RS and uncovers insights into the unexpectedly active biology of the "dead-end" RS.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • CD34 (CD34 molecule) • GDF15 (Growth differentiation factor 15)
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SF3B1 mutation • GDF15 overexpression
6ms
HEPATOCYTE-SPECIFIC GROWTH DIFFERENTIATION FACTOR 15 OVEREXPRESSION AMELIORATES HIGH-FAT DIET-INDUCED OBESITY AND LIVER STEATOSIS VIA INDUCTION OF FIBROBLAST GROWTH FACTOR 21 IN MICE (AASLD 2023)
From a different point of view, it has been reported to improve glucose intolerance due to its potent anti-obesity effect, and NAFLD by enhancing metformin action in diabetic mouse models... GDF15 and FGF21, both liver-derived cellular stress response mitokines, have their blood levels increased in NAFLD. Recently, direct effects of GDF15 on the liver were reported, and in this study, induction of FGF21 expression in the liver was demonstrated under GDF15 overexpression.
Preclinical • IO biomarker
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CCR4 (C-C Motif Chemokine Receptor 4) • GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1) • FGF21 (Fibroblast Growth Factor 21)
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GDF15 overexpression • RET expression
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metformin
over1year
Extracellular vesicles derived from human bone marrow stem cells inhibit acute lymphoblastic leukemia cell growth by inhibiting MAPK pathway via the miR-29b-3p/GDF15 axis. (PubMed, Acta Haematol)
BMSCs-EVs carried miR-29b-3p into ALL cells, upregulated miR-29b-3p, and inhibited GDF15 to suppress the MAPK pathway and further inhibit proliferation and promote apoptosis of ALL cells.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • GDF15 (Growth differentiation factor 15) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
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BCL2 expression • BAX expression • GDF15 overexpression
almost2years
Growth differentiation factor-15 overexpression promotes cell proliferation and predicts poor prognosis in cerebral lower-grade gliomas correlated with hypoxia and glycolysis signature. (PubMed, Life Sci)
GDF15 may promote LGG tumorigenesis that is associated with the hypoxia and glycolysis pathways, and thus could serve as a promising molecular target for LGG prevention and therapy.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • GDF15 (Growth differentiation factor 15)
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GDF15 overexpression • HIF1A expression
almost2years
Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation. (PubMed, Redox Biol)
The reduced ROS production and dsDNA release may be responsible for attenuated AIM2 activation by NAG-1/GDF15 upon fatty acid overload. In conclusion, our results provide evidence that other than regulating lipid homeostasis, NAG-1/GDF15 protects against hepatic steatosis through a novel mechanism via suppressing oxidative stress, mitochondrial damage, dsDNA release, and AIM2 inflammasome activation.
Journal
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GDF15 (Growth differentiation factor 15) • IL18 (Interleukin 18) • AIM2 (Absent In Melanoma 2) • IL1B (Interleukin 1, beta)
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GDF15 overexpression
almost2years
Tumor-derived GDF-15 promotes immune escape of tumors by functional alteration of the myeloid compartment (CIMT 2022)
GDF-15 further polarizes myeloid cells towards a tumor-promoting, anti-inflammatory phenotype.Byinducing a more pro-inflammatory tumor phenotype, anti-GDF-15 antibodies may synergize with other immunotherapeutic agents. A clinical phase 2 trial combining anti-GDF-15 (CTL002) with anti-PD-1 (NCT04725474) is ongoing.
PD(L)-1 Biomarker • IO biomarker
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GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1)
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GDF15 overexpression
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visugromab (CTL-002)
almost2years
Tumor-derived GDF-15 prevents therapy success of checkpoint inhibitors by blocking T-lymphocyte recruitment (CIMT 2022)
Antibodies against GDF-15 therefore support treatments with anti-PD-1 and other immunotherapeutic agents. A clinical phase 2 trial combining anti-GDF-15 (CTL002) with anti-PD-1 (NCT04725474) is ongoing.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1)
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GDF15 overexpression
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visugromab (CTL-002)
almost2years
GDF-15 in tumor-derived exosomes promotes muscle atrophy via Bcl-2/caspase-3 pathway. (PubMed, Cell Death Discov)
Knockdown of GDF-15 in C26 cells decreased the potency of C26 conditioned medium or exosomes in inducing muscle atrophy. These results suggested that GDF-15 in tumor-derived exosomes could contribute to induction of muscle atrophy and also supported the possibility of targeting GDF-15 in treatment of cancer cachexia.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • GDF15 (Growth differentiation factor 15) • CASP3 (Caspase 3)
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GDF15 overexpression
2years
Tumor-derived GDF-15 promotes immune escape of tumors by functional alteration of the myeloid compartment (AACR 2022)
GDF-15 secretion helps tumors to generate a microenvironment that is poorly infiltrated by immune cells. GDF-15 further polarizes myeloid cells towards a tumor-promoting, anti-inflammatory phenotype. By inducing a more pro-inflammatory tumor phenotype, anti-GDF-15 antibodies may synergize with other immunotherapeutic agents.
PD(L)-1 Biomarker • IO biomarker
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GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1)
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GDF15 overexpression
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visugromab (CTL-002)
2years
Mechanism of sensitivity to TPF chemoagents and its potential alternative of erbB2 in oral cancer with GDF15 overexpression. (PubMed, Cancer Sci)
When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI-1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). GDF15 overexpression promotes OSCC proliferation via erbB2 phosphorylation. Thus, ErbB2 inhibitors may represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • GDF15 (Growth differentiation factor 15) • CASP9 (Caspase 9)
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HER-2 overexpression • HER-2 expression • GDF15 overexpression
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cisplatin • docetaxel • 5-fluorouracil • canertinib (CI-1033)
over2years
Tumor-derived GDF-15 prevents therapy success of checkpoint inhibitors by blocking T-lymphocyte recruitment (SITC 2021)
Antibodies against GDF-15 may support treatments with anti-PD-1 and other immunotherapeutic agents. A clinical trial combining anti-GDF-15 (CTL002) with anti-PD-1 (NCT04725474, submitted ID 15073) is ongoing.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1)
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GDF15 overexpression
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visugromab (CTL-002)