P-195 - SPRY2 and response to FOLFOX/CAPOX in metastatic KRAS mutated colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter R. Montal
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors R. Montal1, M.J. Paúles2, F.J. Pérez Martín3, M.-. Merche4, B. Anta1, N. Martínez5, C. Santos1, X. Sanjuan6, D. Azuara7, R. Salazar7, J.M. Rojas1
  • 1Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat/ES
  • 2Interdisciplinary Committee Of Esophagogastric Tumours, Institut Català D'oncologia (ico), Hospitalet de Llobregat, Llobregat/ES
  • 3Hospitalet De Llobregat, IDIBELL, Llobregat/ES
  • 4Institut Català d'Oncologia - IDIBELL, L'Hospitalet de Llobregat/ES
  • 5Insituto de Salud Carlos III - UFIEC, Majadahonda/ES
  • 6Hospital Universitari Bellvitge-IDIBELL, L'Hospitalet de Llobregat/ES
  • 7Institut Catala d'Oncologia-IDIBELL, L'Hospitalet de Llobregat/ES

Abstract

Introduction

Chemotherapy with fluoropyrimidine in combination with either oxaliplatin or irinotecan remains the mainstay of treatment for metastatic colorectal cancer (CRC) but their outcomes are mixed, with no clear validated response predictors. It is known that the docking/scaffold protein SPRY2 modulates the EGFR signaling pathway and also regulates cellular apoptosis in response to DNA damage. Moreover, SPRY2 is up-regulated in CRC, especially in the KRAS mutant status. In this study we are going to assess SPRY2 as a key determinant of response to standard chemotherapy in CRC.

Methods

We designed a retrospective study of metastatic CRC patients harboring KRAS mutation that have been treated in Institut Català d'Oncologia with fluoropyrimidine and oxaliplatin-based chemotherapy (FOLFOX or CAPOX) in the first or second line during the period of 2009-2013. All of them had paraffin sample of the tumor available (primary tumor or metastatic) and clinical information. For each sample, we macrodissected the tumoral from the non-tumoral tissue and extracted the RNA with the High Pure RNA Micro FFPE Kit. The cDNA was done with random hexamers using the GE Healthcare “Ready-To-Go You-prime First-Strand Beads” kit. Finally, quantitative PCR was performed using SYBR Green technology with the SPRY2 and GAPDH (control) primers for the human sequence. With this information we correlated the levels of SPRY2 expression with clinical parameters like response according RECIST v1.1 criteria and progression free survival.

Results

In this pilot study we have analyzed 16 patients. The best radiological response reached was partial response (PR) in 7 patients, stable disease (SD) in 6 patients and progression disease (PD) in 3 patients. The median of progression free survival (mPFS) was 8.5 months (IC95 [2-13]). The median of the expression of SPRY2 (mRNA SPRY2/mRNA GADPH) was 0.07 with a rank of 0.01-0.35. Most of them had levels of expression lower than 0.15 with a mPFS of 8 months but 3 patients had higher levels (2 PR and 1 SD with a mPFS of 13 months). Be mentioned that despite having low values of SPRY2, patients could achieve 38% of PR. The 9 stage IV patients at diagnosis had a median of the expression of SPRY2 of 0.15, higher than the 0.07 of the 7 patients with localized disease at diagnosis (p-value 0.17).

Conclusion

As it has been described before, SPRY2 seems to be overexpressed in more aggressive CRC: in the high-grade undifferentiated tumor in the study of Barbachano et al, and in the stage IV in our study. On the other hand, with this preliminary data, we cannot affirm that the level of expression of SPRY2 is directly linked to tumor response to FOLFOX / CAPOX in CRC. The role of SPRY2 in cancer is complex, orchestrating a multilayered regulatory system and mediating a crosstalk among different signaling pathways that remains to be further elucidated.