Evidence mapPaperPMID 36765947Full record

ArticleCancers2023

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy.

Julieta Afonso, Céline Gonçalves, Marta Costa, Débora Ferreira, Lúcio Santos, Adhemar Longatto-Filho, Fátima Baltazar

Abstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Julieta AfonsoLife and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-9748-3752
Céline GonçalvesLife and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-3713-119X
Marta CostaLife and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-4287-0659
Débora FerreiraCentre of Biological Engineering (CEB), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-0937-4047
Lúcio SantosExperimental Pathology and Therapeutics Group, Research Center of the Portuguese Institute of Oncology (CI-IPOP), 4200-072 Porto, Portugal.
Adhemar Longatto-FilhoLife and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-5779-9752
Fátima BaltazarLife and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.ORCID 0000-0002-1770-4544

Funding

ATTENTION, COGNITION AND DRIVING PERFORMANCE IN SDATR01AG010145 · JEWISH HOSPITAL OF SAINT LOUIS · 1992 to 1994
by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) NORTE-01-0145-FEDER-000055Foundation for Science and Technology (FCT) SFRH/BPD/116784/2016Foundation for Science and Technology (FCT) UIDB/50026/2020Foundation for Science and Technology (FCT) UIDP/50026/2020ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging PPBI-POCI-01-0145-FEDER-022122Liga Portuguesa contra o Cancro - Núcleo Regional do Norte (LPCC-NRN)Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) NORTE-01-0145-FEDER-000039
6 · The paper itself

Abstract

Proliferating cancer cells are able to reprogram their energy metabolism, favouring glycolysis even in the presence of oxygen and fully functioning mitochondria. Research is needed to validate the glycolysis-related proteins as prognostic/predictive biomarkers in urothelial bladder carcinoma (UBC), a malignancy tagged by high recurrence rates and poor response to chemotherapy. Here, we assessed GLUT1, HK2, PFKL, PKM2, phospho-PDH, and LDHA immunoexpression in 76 UBC samples, differentiating among urothelial, fibroblast, and endothelial cells and among normoxic versus hypoxic areas. We additionally studied the functional effects of the HK2 inhibitor 2-deoxy-D-glucose (2DG) in "in vitro" and "in vivo" preclinical UBC models. We showed that the expression of the glycolysis-related proteins is associated with UBC aggressiveness and poor prognosis. HK2 remained as an independent prognostic factor for disease-free and overall survival. 2DG decreased the UBC cell's viability, proliferation, migration, and invasion; the inhibition of cell cycle progression and apoptosis occurrence was also verified. A significant reduction in tumour growth and blood vessel formation upon 2DG treatment was observed in the chick chorioallantoic membrane assay. 2DG potentiated the cisplatin-induced inhibition of cell viability in a cisplatin-resistant subline. This study highlights HK2 as a prognostic biomarker for UBC patients and demonstrates the potential benefits of using 2DG as a glycolysis inhibitor. Future studies should focus on integrating 2DG into chemotherapy design, as an attempt to overcome cisplatin resistance.

Indexed as

2-deoxy-D-glucosecisplatin resistanceglycolysishexokinase 2urothelial bladder carcinomaWarburg effect

Identifiers

PMID36765947
PMCPMC9913750

What Socratic holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.