Informative and useful for a reliable clinical application offer further discussion and variability among the studies. However, considering the utility of gene expression profiling in other tumors, like breast cancer, expression profiling of LARC could be crucial to improve the management of these patients. The results reported here show the expression patterns of response to CRT in LARC patients. Many of the genes were related to the Cellular Growth and Proliferation IPA category, and were over-expressed in patients who responded to treatment. They included a broad range of genes involved in cell-cycle control, DNA synthesis, and c-Myc network such as Gng4, Mapk9, Mcm3, c-Myc, Pola1, Polr2k, and Rrm1, suggesting that LARC cells in CTR- responders present a higher proliferative rate compared to non-responders. Although this hypothesis will need to be confirmed by direct analysis of cell cycle in LARC tumor samples, our results are in agreement with previous studies showing an increased proliferative capacity of tumor cells in patients that respond to treatment. We demonstrated that high Gng4, cMyc, Pola1, and Rrm1 mRNA expression levels were a significant prognostic factor for response to treatment in LARC patients. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with a sensitivity of 60% and a high specificity of 100%. These findings indicate that up-regulation of these genes could represent an independent predictor of response to treatment in LARC patients. It is necessary to further identify the specific mechanisms involved in this process to further understand the response to treatment of LARC. Understanding of the function of c-Myc could increase our understanding of the biology of the responder LARC patients but also may provide a novel therapeutic molecular target for clinical practice. However, the prognostic value for the over-expression of c-Myc mRNA has not been analyzed in rectal tumors, and it should be noted that our cohort of patients is small, and that these results will need to be validated in additional patient cohorts and across multiple institutions. Deregulation and over-expression of c-Myc, in addition to having proliferative effects, is frequently associated with an apoptosis-prone phenotype. Thus opening the possibility of therapeutic intervention due to rapidly proliferating cells are generally more sensitive to chemotherapy. However, the relationship between c-Myc expression and its apoptosis-promoting effects of more clinically relevant chemotherapeutic agents on rectal cancer cells has not been investigated. This could be important since amplification of c-Myc was identified in primary colon tumor patients with increased PF-04217903 disease-free and overall survival after 5-fluorouracil based adjuvant therapy, and amplification of c-Myc was shown to result in a further upregulation of c-Myc “in vitro”. In contrast, c-Myc expression was associated with reduced cancer specific survival in rectal cancer patients.