L. C. Duraes1,2, G. Gantt1,2, J. DeVecchio2, A. Mace1,2, G. Karagkounis1,2, L. Thai1,2, M. F. Kalady1,2 1Cleveland Clinic,Colorectal Department,Cleveland, OH, USA 2Cleveland Clinic,Department Of Stem Cell Biology And Regenerative Medicine – Lerner Research Institute,Cleveland, OH, USA
Introduction:
Patients with a pathologic complete response (pCR) to neoadjuvant chemoradiation have improved oncologic outcomes. Unfortunately only about 20% of patients achieve pCR and ways to improve this number remain elusive. Our laboratory studies genetic factors that may provide insight to the biology underlying response to treatment. Preliminary work by our group has suggested that spermatogenesis associated 20 (SPATA20), which is a gene important for cell differentiation, multicellular organismal development, and spermatogenesis, may be associated with poor outcome in rectal cancer. The purpose of this study is to determine the association between SPATA20 expression and response to neoadjuvant treatment in rectal cancer patients.
Methods:
Thirty-three rectal adenocarcinoma patients treated with neoadjuvant chemoradiation had pretreatment tumor biopsies snap frozen according to an IRB-approved protocol. Total tumor mRNA was extracted from the biopsies and gene expression was determined using high-throughput microarrays on an Illumina platform. Chemoradiation response was evaluated based on American Joint Committee on Cancer (AJCC) criteria (0 – complete response; 1 – small group of tumor cells; 2 – residual cancer outgrown by fibrosis; 3 – minimal tumor kill) and correlated with gene expression levels. Gene expression levels as determined by microarray were validated using quantitative real-time PCR (qPCR). Protein expression was analyzed using immunofluorescence. Statistical analysis was performed and p<0.05 was considered significant.
Results:
SPATA20 expression was significantly decreased in complete responders (AJCC 0) compared to partial and non-responders (AJCC 1-3); and increased in non-responders (AJCC 3) compared to partial and complete responders (AJCC0-2) on microarray analysis. These results were further validated by qPCR (p<0.05) (figure). Furthermore, SPATA20 protein levels were also decreased in complete responders and most elevated in non-responders, as measured by protein immunofluorescence.
Conclusion:
SPATA20 may serve as a novel biomarker in predicting rectal cancer response to chemoradiation. Further prospective validation and exploration into the biological mechanism of how it may contribute to treatment resistance is warranted.
