Open Access
ARTICLE
PNN and KCNQ1OT1 Can Predict the Efficacy of Adjuvant Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer Patients
Andrea Lapucci*†1, Gabriele Perrone*†1, Antonello Di Paolo‡§, Cristina Napoli*†, Ida Landini*†,
Giandomenico Roviello*†, Laura Calosi¶, Antonio Giuseppe Naccarato#, Alfredo Falcone#, Daniele Bani¶, Enrico Mini*†§2, Stefania Nobili*†§2,3
* Department of Health Sciences, University of Florence, Florence, Italy
† DENOTHE Excellence Center, University of Florence, Florence, Italy
‡ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
§ Cancer Pharmacology Working Group of the Italian Society of Pharmacology, Milan, Italy
¶ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
# Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Oncology Research 2020, 28(6), 631-644. https://doi.org/10.3727/096504020X16056983169118
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
PNN and
KCNQ1OT1 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.
PNN and
KCNQ1OT1 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
PNN, 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.
PNN and
KCNQ1OT1
mRNA mean expression levels were significantly higher in tumor compared with normal tissues. Patients with
high
PNN or
KCNQ1OT1 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
PNN or
KCNQ1OT1 gene expression levels. These data confirm our previous findings and underscore the relevance of
PNN and
KCNQ1OT1 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
PNN and
KCNQ1OT1 in CRC, they might also be exploited as potential therapeutic targets.
Keywords
Cite This Article
APA Style
Lapucci, A., Perrone, G., Paolo, A.D., Napoli, C., Landini, I. et al. (2020). pnn and kcnq1ot1 can predict the efficacy of adjuvant fluoropyrimidine-based chemotherapy in colorectal cancer patients. Oncology Research, 28(6), 631-644. https://doi.org/10.3727/096504020X16056983169118
Vancouver Style
Lapucci A, Perrone G, Paolo AD, Napoli C, Landini I, Roviello
, et al. pnn and kcnq1ot1 can predict the efficacy of adjuvant fluoropyrimidine-based chemotherapy in colorectal cancer patients. Oncol Res. 2020;28(6):631-644 https://doi.org/10.3727/096504020X16056983169118
IEEE Style
A. Lapucci et al., "PNN and KCNQ1OT1 Can Predict the Efficacy of Adjuvant Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer Patients," Oncol. Res., vol. 28, no. 6, pp. 631-644. 2020. https://doi.org/10.3727/096504020X16056983169118