Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer

• Published in: PloS one Vol. 8; no. 9; p. e74034
• Main Authors: Palma, Pablo, Cuadros, Marta, Conde-Muíño, Raquel, Olmedo, Carmen, Cano, Carlos, Segura-Jiménez, Inmaculada, Blanco, Armando, Bueno, Pablo, Ferrón, J Antonio, Medina, Pedro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.09.2013; Public Library of Science (PLoS)
• Subjects: Adjuvant chemotherapy; Adult; Aged; Analysis; Apoptosis; Artificial intelligence; Biochemistry; Biomarkers, Tumor; Blood; Blood cells; Cancer; Cancer genetics; Cancer therapies; Chemoradiotherapy; Chemotherapy; Colon; Colorectal cancer; Computer science; DNA microarrays; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Genes; Histocompatibility antigen HLA; Humans; Hybridization; Immune response; Immune system; Immunology; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - radiation effects; Male; Medical research; Middle Aged; Molecular biology; Neoplasm Staging; Organs; Patients; Peripheral blood mononuclear cells; Prognosis; Quality; Radiation therapy; Rectal Neoplasms - drug therapy; Rectal Neoplasms - genetics; Rectal Neoplasms - radiotherapy; Rectum; Regression analysis; Reproducibility of Results; Ribonucleic acid; RNA; Statistical analysis; Statistical methods; Surgery; Treatment Outcome; Vascular endothelial growth factor; United States > US; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074034

Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced rectal cancer. Moreover, our investigation added further evidence to the importance of mononuclear cells' mediated response in the neoadjuvant treatment of rectal cancer.