@Article{096504020X16056983169118,
AUTHOR = {Andrea Lapucci, Gabriele Perrone, Antonello Di Paolo, Cristina Napoli, Ida Landini, 
Giandomenico Roviello, Laura Calosi, Antonio Giuseppe Naccarato, Alfredo Falcone, Daniele Bani, Enrico Mini, Stefania Nobili},
TITLE = {<i>PNN</i> and <i>KCNQ1OT1</i> Can Predict the Efficacy of Adjuvant  Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer Patients},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {6},
PAGES = {631--644},
URL = {http://www.techscience.com/or/v28n6/48500},
ISSN = {1555-3906},
ABSTRACT = {The benefit of adjuvant chemotherapy in the early stages of colorectal cancer (CRC) is still disappointing and 
the prediction of treatment outcome quite difficult. Recently, through a transcriptomic approach, we evidenced 
a role of <i>PNN</i> and <i>KCNQ1OT1</i> gene expression in predicting response to fluoropyrimidine-based adjuvant 
chemotherapy in stage III CRC patients. Thus, the aim of this study was to validate in an independent cohort of 
stages II–III CRC patients our previous findings. <i>PNN</i> and <i>KCNQ1OT1</i> mRNA expression levels were evaluated in 74 formalin-fixed paraffin-embedded tumor and matched normal mucosa samples obtained by stages 
II–III CRC patients treated with fluoropyrimidine-based adjuvant chemotherapy. PININ, the protein encoded 
by <i>PNN</i>, was immunohistochemically evaluated in 15 tumor and corresponding normal mucosa samples, 
selected on the basis of a low, medium, or high mRNA expression tumor/mucosa ratio. <i>PNN</i> and <i>KCNQ1OT1</i>
mRNA mean expression levels were significantly higher in tumor compared with normal tissues. Patients with 
high <i>PNN</i> or <i>KCNQ1OT1</i> tumor mRNA levels according to ROC-based cutoffs showed a shorter disease-free 
survival (DFS) compared with patients with low tumor mRNA gene expression. Also, patients with tumor 
mRNA expression values of both genes below the identified cutoffs had a significantly longer DFS compared 
with patients with the expression of one or both genes above the cutoffs. In a representative large cohort of 
stages II–III CRC untreated patients retrieved from GEO datasets, no difference in DFS was observed between 
patients with high and low <i>PNN</i> or <i>KCNQ1OT1</i> gene expression levels. These data confirm our previous findings and underscore the relevance of <i>PNN</i> and <i>KCNQ1OT1</i> expression in predicting DFS in early stages of 
CRC treated with fluoropyrimidine-based adjuvant chemotherapy. If further validated in a prospective case 
series, both biomarkers could be used to identify patients who benefit from this treatment and to offer alternative chemotherapy regimens to potential unresponsive patients. In relation to the suggested biological role of 
<i>PNN</i> and <i>KCNQ1OT1</i> in CRC, they might also be exploited as potential therapeutic targets.},
DOI = {10.3727/096504020X16056983169118}
}