Microarray Profiling of Mononuclear Peripheral Blood Cells Identifies Novel Candidate Genes Related to Chemoradiation Response in Rectal Cancer

Abstract

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.

Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

“…Pre-treatment peripheral blood mononuclear cells in 35 cases of locally advanced rectal cancers treated with long-course therapy were subjected to microarray gene profiling [67]. Differentially expressed genes were BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2 and ZFP26.…”

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

“…However, only bromodomain PHD finger transcription factor, which encodes for a transcription factor that regulates apoptosis, was confirmed using qRT-PCR. 74 …”

Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

“…Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making their use as therapy predictors possible. Furthermore, the importance of the immune response in radiosensitivity of solid organs led Palma et al [ 8 ] to hypothesize that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to CRT in LARC. Thirty-five 35 patients with locally advanced rectal cancer were recruited initially to perform the study.…”

“…It is clear that there is a biological basis as to why some tumors respond to CRT and that biology could be related to the tumor, the patient, or both. In this context, the genes identified in Mononuclear Peripheral Blood Cells could offer new insights into the immune system's dysregulation in LARC [ 8 ] and should be further investigated. Furthermore, the answer may not lie strictly in the genome of the tumor but could represent epigenetic factors, and these would also need to be explored.…”

“…In addition, patients who are unlikely to respond could be offered alternative approaches to therapy. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in LARC treated with neoadjuvant CRT [ 7 , 8 ]. The goal of this review is to examine the current literature for the most commonly researched biomarkers for predicting outcome to neoadjuvant CRT in LARC patients.…”