Sorry, you need to enable JavaScript to visit this website.

A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer

TitleA combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2019
AuthorsButtarelli, M., Babini G., Raspaglio G., Filippetti F., Battaglia A., Ciucci A., Ferrandina G., Petrillo M., Marino Carmela, Mancuso Mariateresa, Saran A., Villani Maria Elena, Desiderio Angiola, D'Ambrosio C., Scaloni A., Scambia G., and Gallo D.
JournalJournal of experimental & clinical cancer research : CR
Keywordsadult, aged, Annexin A2, antineoplastic agent, Antineoplastic Agents, ANXA2 gene, ANXA2 protein, article, biological marker, Biomarkers, cell cycle protein, Cell Cycle Proteins, cell death, Cell Survival, chemoradiotherapy, cisplatin, Female, gene expression profiling, gene expression regulation, gene identification, genetics, human, human cell, human tissue, Humans, in vitro study, Intracellular Signaling Peptides and Proteins, lipocortin 2, metabolism, Middle Aged, N-myc downstream-regulated gene 1 protein, NDRG1 gene, neoadjuvant therapy, Neoplastic, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1, PARP1 protein, Pathology, Poly (ADP-Ribose) Polymerase-1, priority journal, Proteomics, Radiation Tolerance, random forest, signal peptide, STAT1 gene, STAT1 protein, STAT1 Transcription Factor, transcriptome, treatment response, Tumor, tumor biopsy, tumor marker, Uterine Cervical Neoplasms, uterine cervix cancer, uterine cervix tumor, young adult

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.


cited By 0

Citation KeyButtarelli2019279