Abstract 42: Identification of gene expression patterns distinguishing responders and non-responders to induction chemotherapy in sinonasal undifferentiated carcinoma
Authors: Takahashi Yoko , Bell Diana , Gleber-Netto Frederico O. , Xie Tong-Xin , Roberts Dianna , Pickering Curtis , Myers Jeffrey N. , Hanna Ehab Y. 
Published: December 2017

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer that arises in the nasal cavity and paranasal sinuses. Despite aggressive multimodal therapy the prognosis remains poor, and the median survival time is less than 18 months. Because of its locally advanced nature, cisplatin-based induction chemotherapy has been used in our institution to downstage unresectable tumors before definitive surgery or radiation therapy. Interestingly, our previous study showed that response to induction chemotherapy is a prognostic indicator and may be used to select patients for definitive local treatment. In this study, we performed gene expression analysis on SNUC specimens to identify molecular markers to predict/distinguish between responders and non-responders to induction chemotherapy.

Materials and Methods: Twenty-seven formalin-fixed paraffin-embedded samples from 24 patients treated at MD Anderson Cancer Center between 1999 to 2016 were used in this study. Among them, 12 specimens were treatment-naïve. Gene expression analysis was performed on an HTG EdgeSeq Oncology Biomarker Panel. Unsupervised clustering analysis and Mann-Whitney test were performed using JMP software and IBM SPSS Statistics 23, previously. Pathway analysis was performed using Ingenuity Pathway Analysis.

Results: First, we attempted to identify a set of genes which could predict response to induction chemotherapy. Unfortunately, unsupervised clustering analysis on treatment-naïve specimen was incapable of distinguishing between responders and non-responders. However, using discriminant analysis we succeeded in finding genes classifying patients into responders and non-responders. Then we studied the tumor specimens harvested after induction chemotherapy; differentially expressed genes between the two groups (Mann-Whitney test; p&lt;0.05) were analyzed for pathway analysis. Multiple upstream regulators related to cell survival and proliferation including Transforming growth factor beta 1 were predicted to be activated in the non-responders' specimens.

Conclusions: Our study revealed the possibility that cell survival and proliferation pathways are upregulated in non-responders to induction chemotherapy in SNUC. This finding suggests that non-responders to induction chemotherapy might be treated by inhibiting those pathways. Our comprehensive gene expression study is a significant step towards developing new therapeutic approaches in SNUC.

Citation Format: Yoko Takahashi, Diana Bell, Frederico O. Gleber-Netto, Tong-Xin Xie, Dianna Roberts, Curtis Pickering, Jeffrey N. Myers, Ehab Y. Hanna. Identification of gene expression patterns distinguishing responders and non-responders to induction chemotherapy in sinonasal undifferentiated carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 42.