Evidence map›Paper›PMID 37667354›Full record

ArticleMolecular cancer2023

Identification of multidrug chemoresistant genes in head and neck squamous cell carcinoma cells.

Neha Khera, Asvika Soodhalaagunta Rajkumar, Khlood Abdulkader M Alkurdi, Zhiao Liu, Hong Ma, Ahmad Waseem, Muy-Teck Teh

Open access · goldAbstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Metabolic-epigenetic reprogrammingActa pharmaceutica Sinica. B · 2026
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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 at 2 institutions in 2 countries.

Neha KheraCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK.
Asvika Soodhalaagunta RajkumarCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK.
Khlood Abdulkader M AlkurdiCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK.
Zhiao LiuCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK.
Hong MaChina-British Joint Molecular Head and Neck Cancer Research Laboratory, Affiliated Stomatological Hospital of Guizhou Medical University, Guizhou, China.
Ahmad WaseemCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK.
Muy-Teck TehCentre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizard Building, 4, Newark Street, London, E1 2AT, UK. m.t.teh@qmul.ac.uk.
Queen Mary University of London · GBAffiliated Hospital of Guizhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance.

Indexed as

CisplatinHead and Neck NeoplasmsCell LineForkhead Transcription FactorsHumansNIMA-Related KinasesSignal TransductionSquamous Cell Carcinoma of Head and NeckCisplatinForkhead Transcription FactorsFOXO6 protein, humanNEK2 protein, humanNIMA-Related KinasesChemosensitizationCisplatinDrug-gene interactionINHBAMultidrug chemoresistanceNEK2Oral cancerSquamous cell carcinomas

Identifiers

PMID37667354
PMCPMC10476423
OpenAlexW4386418094

What OpenQuestion holds

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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 OpenQuestion graph.