Evidence map›Paper›PMID 36233276›Full record

ArticleInternational journal of molecular sciences2022

Multi-Omics Analysis Revealed a Significant Alteration of Critical Metabolic Pathways Due to Sorafenib-Resistance in Hep3B Cell Lines.

Kholoud Y I Abushawish, Sameh S M Soliman, Alexander D Giddey, Hamza M Al-Hroub, Muath Mousa, Karem H Alzoubi, Waseem El-Huneidi, Eman Abu-Gharbieh, Hany A Omar, Sara M Elgendy and 3 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% of its field
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
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

13 authors at 2 institutions in 2 countries.

Kholoud Y I AbushawishCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0001-5488-8680
Sameh S M SolimanCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0002-7691-615X
Alexander D GiddeyResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Hamza M Al-HroubResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Muath MousaResearch Institute of Science and Engineering, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Karem H AlzoubiCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Waseem El-HuneidiResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0002-1580-2589
Eman Abu-GharbiehResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0002-5972-0681
Hany A OmarCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0002-4670-8149
Sara M ElgendyCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Yasser BustanjiResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0003-1315-0609
Nelson C SoaresCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
Mohammad H SemreenCollege of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.ORCID 0000-0002-0169-7538
University of Sharjah · AEUniversity of Jordan · JO

Funding

University of Sharjah 1901110133University of Sharjah 2001110138
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the second prominent cause of cancer-associated death worldwide. Usually, HCC is diagnosed in advanced stages, wherein sorafenib, a multiple target tyrosine kinase inhibitor, is used as the first line of treatment. Unfortunately, resistance to sorafenib is usually encountered within six months of treatment. Therefore, there is a critical need to identify the underlying reasons for drug resistance. In the present study, we investigated the proteomic and metabolomics alterations accompanying sorafenib resistance in hepatocellular carcinoma Hep3B cells by employing ultra-high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS). The Bruker Human Metabolome Database (HMDB) library was used to identify the differentially abundant metabolites through MetaboScape 4.0 software (Bruker). For protein annotation and identification, the Uniprot proteome for Homo sapiens (Human) database was utilized through MaxQuant. The results revealed that 27 metabolites and 18 proteins were significantly dysregulated due to sorafenib resistance in Hep3B cells compared to the parental phenotype. D-alanine, L-proline, o-tyrosine, succinic acid and phosphatidylcholine (PC, 16:0/16:0) were among the significantly altered metabolites. Ubiquitin carboxyl-terminal hydrolase isozyme L1, mitochondrial superoxide dismutase, UDP-glucose-6-dehydrogenase, sorbitol dehydrogenase and calpain small subunit 1 were among the significantly altered proteins. The findings revealed that resistant Hep3B cells demonstrated significant alterations in amino acid and nucleotide metabolic pathways, energy production pathways and other pathways related to cancer aggressiveness, such as migration, proliferation and drug-resistance. Joint pathway enrichment analysis unveiled unique pathways, including the antifolate resistance pathway and other important pathways that maintain cancer cells' survival, growth, and proliferation. Collectively, the results identified potential biomarkers for sorafenib-resistant HCC and gave insights into their role in chemotherapeutic drug resistance, cancer initiation, progression and aggressiveness, which may contribute to better prognosis and chemotherapeutic outcomes.

Indexed as

Antineoplastic AgentsCarcinoma, HepatocellularFolic Acid AntagonistsLiver NeoplasmsAlanineAmino AcidsBiomarkersCalpainCell Line, TumorCell ProliferationDrug Resistance, NeoplasmGlucoseHumansL-Iditol 2-DehydrogenaseMetabolic Networks and PathwaysNucleotidesAlanineAmino AcidsAntineoplastic AgentsBiomarkersCalpainFolic Acid AntagonistsGlucoseL-Iditol 2-DehydrogenaseNucleotidesPhosphatidylcholinesProlineProtein Kinase InhibitorsProteomeSorafenibSuccinic AcidSuperoxide DismutaseTyrosineUbiquitin ThiolesteraseUridine Diphosphatemetabolomicsparental Hep3B cellsproteomicssorafenib-resistant Hep3B cellsUHPLC-QTOF-MS

Identifiers

PMID36233276
PMCPMC9569810
OpenAlexW4303946191

What Socratic holds

Textmetadata
LicenceCC BY
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.