Gene expression profile reveals a nodal status signature in rectal carcinomas

Background

A significant number (> 50%) of patients with rectal cancer presents locally advanced disease at diagnosis, which are associated with high risk of recurrence. Positive nodal status after treatment was recently proven to be associated with poor prognosis in these cases, even after primary tumor regression. Herein, the gene expression profiling of tumor biopsies was assessed aiming to identify a gene signature capable to predict the nodal status in rectal carcinomas.

Methods

Large scale transcriptome analysis of 33 pre-treatment rectal adenocarcinoma biopsies was evaluated using the GeneChip Human Transcriptome Array 2.0 (Affymetrix, USA). Formalin fixed paraffin embedded tissue was macrodissected and the RNA was extracted using the RecoverAll™ Total Nucleic Acid Isolation Kit (ThermoFisher, USA). Data were normalized using Expression Console Software (Affymetrix). Differentially expressed genes in relation to lymph node status were assessed using BRB array tools software, establishing a two-tailed P-value 

Results

Five of 33 patients presented lymph node positivity. A signature of 88 coding transcripts was able to differentiate the cases according to lymph node status after surgery. Among these genes, a set of histones (HIST1H4I, HIST1H2BK, HIST1H2BJ, HIST1H3F, HIST1H2BD, H2AFX) was overexpressed in patients with positive nodal status. These cases also presented no pathological response to chemoradiotherapy and worse prognosis features. Additional differentially expressed transcripts were also related to chromatin assembly and disassembly and to nucleic acid binding.

Conclusions

The regulation of chromatin condensation is a putative mechanism associated with response to treatment as well as with lymph node positivity prediction in rectal cancer samples. More importantly, the discrepancy in nuclear structure regulation could be detected upon diagnosis, which can be used as a tool to predict outcomes and design new treatment strategies for rectal cancer patients.

Clinical trial identification

Legal entity responsible for the study

Silvia Regina Rogatto

Funding

INCiTO (FAPESP 2008/57887 and CNPq 573589/09-9) and FAPESP (2014/06323-9).

Disclosure

All authors have declared no conflicts of interest.