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Cited by 10Head and Neck Cancer StudiesBreast Cancer Treatment StudiesGene expression and cancer classification

A Head and Neck Cancer Tumor Response-Specific Gene Signature for Cisplatin, 5-Fluorouracil Induction Chemotherapy Fails with Added Taxanes

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Tomkiewicz, Céline, Hans, Stéphane, Mucchielli, Marie Hélène, Agier, Nicolas, Delacroix, Hervé, Marisa, Laetitia, Brasnu, Daniel, Aggerbeck, Lawrence P. +3 more·2012·PLoS ONE
DOI 10.1371/journal.pone.0047170PMC PMC3467249
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Abstract

BACKGROUND: It is a major clinical challenge to predict which patients, with advanced stage head and neck squamous cell carcinoma, will not exhibit a reduction in tumor size following induction chemotherapy in order to avoid toxic effects of ineffective chemotherapy and delays for instituting other therapeutic options. Further, it is of interest to know to what extent a gene signature, which identifies patients with tumors that will not respond to a particular induction chemotherapy, is applicable when additional chemotherapeutic agents are added to the regimen. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes that predict tumor resistance to induction with cisplatin/5-fluorouracil (PF) or PF and a taxane, we analyzed patient tumor biopsies with whole genome microarrays and quantitative reverse transcriptase-PCR (TLDA) cards. A leave one out cross-validation procedure allowed evaluation of the prediction tool. A ten-gene microarray signature correctly classified 12/13 responders and 7/10 non-responders to PF (92% specificity, 82.6% accuracy). TLDA analysis (using the same classifier) of the patients correctly classified 12/12 responders and 8/10 non-responders (100% specificity, 90.9% accuracy). Further, TLDA analysis correctly predicted the response of 5 new patients and, overall, 12/12 responders and 13/15 non-responders (100% specificity, 92.6% accuracy). The protein products of the genes constituting the signature physically associate with 27 other proteins, involved in regulating gene expression, constituting an interaction network. In contrast, TLDA-based prediction (with the same gene signature) of responses to induction with PF and either of two taxanes was poor (0% specificity, 25% accuracy and 33.3% specificity, 25% accuracy). CONCLUSIONS/SIGNIFICANCE: Successful transfer of the microarray-based gene signature to an independent, PCR-based technology suggests that TLDA-based signatures could be a useful hospital-based technology for determining therapeutic options. Although highly specific for tumor responses to PF induction, the gene signature is unsuccessful when taxanes are added. The results illustrate the subtlety in developing "personalized medicine".

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  • Another cisplatin response signature, extracted from 26 head and neck cancer patients with complete clinical response or non-response to cisplatin and 5-FU, contains 10 genes that do not overlap with CisSig.

    “Another cisplatin response signature, extracted from 26 head and neck cancer patients with complete clinical response or non-response to cisplatin and 5-FU contains 10 genes that do not overlap with CisSig34.”

    From Exploiting convergent phenotypes to derive a pan-cancer cisplatin response gene expression signature (2023) · cites this paper as [34]

    The Results section, “A Gene Signature for Response to Cisplatin/5-fluorouracil Induction” (page not provided), reports a ten-gene signature derived from biopsies of 23 patients treated with cisplatin and 5-FU, not 26. It distinguishes complete clinical responders from non-responders. Our copy does not address whether those genes overlap with CisSig. (LLM, conf=0.89)

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Authors
Tomkiewicz, C., Hans, S., Mucchielli, M. H., Agier, N., Delacroix, H., Marisa, L., Brasnu, D., Aggerbeck, L. P., Badoual, C., Barouki, R., & Aggerbeck, M.
Affiliations
  • Inserm (FR)
  • Sorbonne Paris Cité (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Université Paris-Sud (FR)
  • Hôpital Necker-Enfants Malades (FR)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-10-09
Volume
7
Issue
10
Pages
e47170
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0047170
PMC
PMC3467249
OpenAlex
W1987241849
Cited by
10
References
1
Citations by year
2023: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2014: 2
FWCI
0.63
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • Université Paris Descartes
Topics
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
head and neck squamous cell carcinoma, cisplatin, 5-fluorouracil, induction chemotherapy, taxanes, gene expression signatures, predictive biomarkers, tumor response prediction, transcriptome signature, protein-protein interaction network, personalized medicine
MeSH terms
Adult, Aged, Cisplatin, Fluorouracil, Head and Neck Neoplasms, Humans, Male, Middle Aged, Protein Binding, Gene Expression Regulation, Neoplastic, Reverse Transcriptase Polymerase Chain Reaction, Taxoids, Induction Chemotherapy

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