Palma, PabloCano, CarlosConde-Muiño, RaquelComino, AnaBueno, PabloFerrón, J AntonioCuadros, Marta2015-05-282015-05-282014-11-07Palma P, Cano C, Conde-Muiño R, Comino A, Bueno P, Ferrón JA, et al. Expression profiling of rectal tumors defines response to neoadjuvant treatment related genes. PLoS ONE. 2014; 9(11):e112189http://hdl.handle.net/10668/1898Journal Article; Research Support, Non-U.S. Gov't;To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.enQuimiorradioterapiaRadiotoleranciaNeoplasias del rectoPeríodo preoperatorioResultado del tratamientoPerfiles de expresión génicaMarcadores biológicosTratamiento neoadyuvanteAnálisis de secuencias por matrices de oligonucleótidosMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy::ChemoradiotherapyMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Radiation ToleranceMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal NeoplasmsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Perioperative Period::Preoperative PeriodMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression ProfilingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and ProteinsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic::TranscriptomeMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant TherapyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Microchip Analytical Procedures::Microarray Analysis::Oligonucleotide Array Sequence AnalysisExpression profiling of rectal tumors defines response to neoadjuvant treatment related genes.research article25380052open access10.1371/journal.pone.01121891932-6203PMC4224421