TY - JOUR
T1 - The relevance of prelamin A and RAD51 as molecular biomarkers in cervical cancer
AU - Leonardi, Simona
AU - Buttarelli, Marianna
AU - De Stefano, Ilaria
AU - Ferrandina, Maria Gabriella
AU - Petrillo, Marco
AU - Babini, Gabriele
AU - Scambia, Giovanni
AU - Marino, Carmela
AU - Mancuso, Mariateresa
AU - Gallo Guido, Daniela
PY - 2017
Y1 - 2017
N2 - Along with their role in the maintenance of nuclear architecture, nuclear lamins also control genomic stability, DNA damage repair, transcription, cell proliferation, differentiation and senescence. Recent reports reveal that prelamin A-processing defects play a role in cancer development by impacting on transcription of key players in the maintenance of the genome stability, including RAD51. Here, we performed a 'proof of concept' study evaluating the role of prelamin A and RAD51 expression in clinical outcome of cervical cancer patients. We analyzed biomarker expression by immunohistochemistry in tumor material from locally advanced cervical cancer (LACC) patients (n=66) and correlated data with clinicopathological parameters and with response to neoadjuvant chemoradiation (CT/RT). In LACC patients who underwent neoadjuvant CT/RT the percentage of cases showing high prelamin A levels was greater in patients who completely responded to treatment (25 of 40, 62.5%) than in patients with macroscopic residual tumor (6 of 26, 23.1%, p=0.0024). Conversely, patients showing high RAD51 expression were less likely to respond to treatment (14 of 26, 53.8%) than were those with low protein levels (12 of 40, 30%, p=0.072). Only prelamin A retained an independent role in predicting response to treatment (p=0.003), while RAD51 approached statistical significance (p=0.07). Notably, high RAD51 expression highly significantly predicted poor outcome, emerging as an independent prognostic factor for disease free survival (p=0.038), while approaching statistical significance for overall survival (p=0.09). Our findings provide a framework for future prospective studies investigating molecular predictors of response to neoadjuvant chemoradiotherapy in LACC patients.
AB - Along with their role in the maintenance of nuclear architecture, nuclear lamins also control genomic stability, DNA damage repair, transcription, cell proliferation, differentiation and senescence. Recent reports reveal that prelamin A-processing defects play a role in cancer development by impacting on transcription of key players in the maintenance of the genome stability, including RAD51. Here, we performed a 'proof of concept' study evaluating the role of prelamin A and RAD51 expression in clinical outcome of cervical cancer patients. We analyzed biomarker expression by immunohistochemistry in tumor material from locally advanced cervical cancer (LACC) patients (n=66) and correlated data with clinicopathological parameters and with response to neoadjuvant chemoradiation (CT/RT). In LACC patients who underwent neoadjuvant CT/RT the percentage of cases showing high prelamin A levels was greater in patients who completely responded to treatment (25 of 40, 62.5%) than in patients with macroscopic residual tumor (6 of 26, 23.1%, p=0.0024). Conversely, patients showing high RAD51 expression were less likely to respond to treatment (14 of 26, 53.8%) than were those with low protein levels (12 of 40, 30%, p=0.072). Only prelamin A retained an independent role in predicting response to treatment (p=0.003), while RAD51 approached statistical significance (p=0.07). Notably, high RAD51 expression highly significantly predicted poor outcome, emerging as an independent prognostic factor for disease free survival (p=0.038), while approaching statistical significance for overall survival (p=0.09). Our findings provide a framework for future prospective studies investigating molecular predictors of response to neoadjuvant chemoradiotherapy in LACC patients.
KW - Cervix
KW - Chemoradiotherapy
KW - DNA repair
KW - LACC
KW - Lamin A/C
KW - Oncology
KW - Cervix
KW - Chemoradiotherapy
KW - DNA repair
KW - LACC
KW - Lamin A/C
KW - Oncology
UR - http://hdl.handle.net/10807/112829
UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5b%5d=21686&path%5b%5d=68837
U2 - 10.18632/oncotarget.21686
DO - 10.18632/oncotarget.21686
M3 - Article
SN - 1949-2553
VL - 8
SP - 94247
EP - 94258
JO - Oncotarget
JF - Oncotarget
ER -