(Higher Education Institutional Excellence Programme of the Ministry for Innovation
and Technology in Hungary, within the framework of the Bionic thematic programme of
the Semmelweis University)
Szakterületek:
Onkológia
Orvos- és egészségtudomány
Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors
with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various
diseases and modulate therapy response as well. The aim of this study was to identify
predictive miRNAs in platinum-treated SCCs. Methods: miRNA expression data of platinum-treated
head and neck (HNSC), cervical (CESC) and lung (LUSC) cancer were collected from the
TCGA repositories. Treatment response was defined based on presence or absence of
disease progression at 18 months. Responder and nonresponder cohorts were compared
using Mann–Whitney and Receiver Operating Characteristic tests. Logistic regression
was developed to establish a predictive miRNA signature. Significance was set at FDR
< 5%. Results: The integrated database includes 266 SCC patient samples with platinum-based
therapy and available follow-up. We uncovered 16, 103, and 9 miRNAs correlated to
chemotherapy response in the CESC, HNSC, and LUSC cohorts, respectively. Eight miRNAs
overlapped between the CESC and HNSC subgroups, and three miRNAs overlapped between
the LUSC and HNSC subgroups. We established a logistic regression model in HNSC and
CESC which included six miRNAs: hsa-miR-5586 (Exp (B): 2.94, p = 0.001), hsa-miR-632
(Exp (B): 10.75, p = 0.002), hsa-miR-2355 (Exp (B): 0.48, p = 0.004), hsa-miR-642a
(Exp (B): 2.22, p = 0.01), hsa-miR-101-2 (Exp (B): 0.39, p = 0.013) and hsa-miR-6728
(Exp (B): 0.21, p = 0.016). The model using these miRNAs was able to predict chemotherapy
resistance with an AUC of 0.897. Conclusions: We performed an analysis of RNA-seq
data of squamous cell carcinomas samples and identified significant miRNAs correlated
to the response against platinum-based therapy in cervical, head and neck, and lung
tumors.