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
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.
- Molecular biomarkers
- Personalized medicine