Expression profiling of rectal tumors defines response to neoadjuvant treatment related genes.
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.
Division of Colon & Rectal Surgery, Virgen de las Nieves Hospital (HUVN), Granada, Spain.
Pablo
P
Palma
Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain.
Carlos
C
Cano
Division of Colon & Rectal Surgery, Virgen de las Nieves Hospital (HUVN), Granada, Spain.
Raquel
R
Conde-Muiño
Department of Surgical Research, Virgen de las Nieves Hospital (HUVN), Granada, Spain.
Ana
A
Comino
Department of Surgical Research, Virgen de las Nieves Hospital (HUVN), Granada, Spain.
Pablo
P
Bueno
Division of Colon & Rectal Surgery, Virgen de las Nieves Hospital (HUVN), Granada, Spain; Department of Surgical Research, Virgen de las Nieves Hospital (HUVN), Granada, Spain.
J Antonio
JA
Ferrón
Department of Biochemistry and Molecular Biology III e Immunology, University of Granada, Granada, Spain; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of de Granada/Junta de Andalucía, Granada, Spain.
Marta
M
Cuadros
D000368:Aged; D059248:Chemoradiotherapy; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome