A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer.
Adult
Aged
Annexin A2
/ genetics
Antineoplastic Agents
/ therapeutic use
Biomarkers, Tumor
Cell Cycle Proteins
/ genetics
Chemoradiotherapy
Cisplatin
/ therapeutic use
Female
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Middle Aged
Neoadjuvant Therapy
Poly (ADP-Ribose) Polymerase-1
/ metabolism
Radiation Tolerance
STAT1 Transcription Factor
/ genetics
Transcriptome
Uterine Cervical Neoplasms
/ genetics
Young Adult
Cervix
LACC
Molecular biomarkers
Personalized medicine
Proteomics
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
26 Jun 2019
26 Jun 2019
Historique:
received:
26
03
2019
accepted:
04
06
2019
entrez:
28
6
2019
pubmed:
28
6
2019
medline:
18
12
2019
Statut:
epublish
Résumé
A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor. To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer. We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1 (NDRG1) and signal transducer and activator of transcription 1 (STAT1) as biomarkers of LACC patients' responsiveness to CRT. The dataset collected through qPCR on these genes was used as training dataset to implement a Random Forest algorithm able to predict the response of new patients to this treatment. Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. Our results define a predictive gene signature that can help in cervical cancer patient stratification, thus providing a useful tool towards more personalized treatment modalities.
Sections du résumé
BACKGROUND
BACKGROUND
A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor.
METHODS
METHODS
To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer.
RESULTS
RESULTS
We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1 (NDRG1) and signal transducer and activator of transcription 1 (STAT1) as biomarkers of LACC patients' responsiveness to CRT. The dataset collected through qPCR on these genes was used as training dataset to implement a Random Forest algorithm able to predict the response of new patients to this treatment. Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells.
CONCLUSIONS
CONCLUSIONS
Our results define a predictive gene signature that can help in cervical cancer patient stratification, thus providing a useful tool towards more personalized treatment modalities.
Identifiants
pubmed: 31242951
doi: 10.1186/s13046-019-1268-y
pii: 10.1186/s13046-019-1268-y
pmc: PMC6595690
doi:
Substances chimiques
ANXA2 protein, human
0
Annexin A2
0
Antineoplastic Agents
0
Biomarkers, Tumor
0
Cell Cycle Proteins
0
Intracellular Signaling Peptides and Proteins
0
N-myc downstream-regulated gene 1 protein
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
279Subventions
Organisme : Regione Campania
ID : PO FESR 2014-2020
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