Biomarkers Of Chemoradiotherapy Response In Rectal Carcinomas
Luisa MATOS DO CANTO, A.C. Camargo Cancer Center, Brazil
ROGATTO S. 1,4
, CATIN B. 3
, AGUIAR JR. S. 3
, BEGNAMI M. 2
1 CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil
2 Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil
3 Department of Surgical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
4 Department of Clinical Cancer Genetics, Vejle Hospital - University of Odense, Vejle, Denmark
Purpose: The large scale gene expression analysis was performed in rectal carcinoma (ReCa) from patients that undergo neoadjuvant radio- or radiochemotherapy (nCRT) aiming to identify biomarkers of pathological complete response (pCR).
Methods: The transcriptome analyses (GeneChip® Human Transcriptome Array 2.0, Affymetrix, USA) were performed in tumor biopsies from 29 patients with ReCa: 21 with pathological incomplete response (pIR) and 8 with complete response (pCR). Data were normalized and analyzed (Transcriptome Analysis Console 3.0, Affymetrix) (ANOVA p<0.05) according to the manufacturer´s recommendations.
Results: The data comparison between pIR and pCR cases resulted in 193 genes differentially expressed; 179 of them showed lower expression levels in pCR patients. Among the genes downexpressed in pCR, 15 are related to histone modification (HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L, HIST4H4, HIST2H3A, HIST2H3C, and HIST2H3D), suggesting the involvement of epigenetic alterations in the nCRT response.
Conclusions: Lower expression levels of these particular histones could result in a less tightly bound to DNA and thus making the chromatin more accessible to radio and chemotherapy. Patients with pCR have better prognosis than those with residual disease. These patients could be spared of a highly morbid surgery if the response to nCRT were accurately identified before the procedure.
Financial Support: INCiTO (FAPESP 2008/57887 and CNPq 573589/08-9) and FAPESP (2014/06323-9)