TY - JOUR
T1 - A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer
AU - Buttarelli, Marianna
AU - Babini, Gabriele
AU - Raspaglio, Giuseppina
AU - Filippetti, Flavia
AU - Battaglia, Alessandra
AU - Ciucci, Alessandra
AU - Ferrandina, Maria Gabriella
AU - Petrillo, Marco
AU - Marino, Carmela
AU - Mancuso, Mariateresa
AU - Saran, Anna
AU - Villani, Maria Elena
AU - Desiderio, Angiola
AU - D'Ambrosio, Chiara
AU - Scaloni, Andrea
AU - Scambia, Giovanni
AU - Gallo, Daniela
PY - 2019
Y1 - 2019
N2 - A combined ANXA2-NDRG1-STAT1 gene signature predicts response to
chemoradiotherapy in cervical cancer.
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: 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: 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: 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.
AB - A combined ANXA2-NDRG1-STAT1 gene signature predicts response to
chemoradiotherapy in cervical cancer.
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: 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: 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: 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.
KW - Cervix
KW - LACC
KW - Molecular biomarkers
KW - Personalized medicine
KW - Proteomics
KW - Cervix
KW - LACC
KW - Molecular biomarkers
KW - Personalized medicine
KW - Proteomics
UR - http://hdl.handle.net/10807/138187
U2 - 10.1186/s13046-019-1268-y
DO - 10.1186/s13046-019-1268-y
M3 - Article
SN - 0392-9078
VL - 38
SP - 279-N/A
JO - JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
JF - JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
ER -