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MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)-A*2402-restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA-A*2402-matched group and 10 patients from the HLA-A*2402-unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402-matched group with high expression of miR-196b-5p and low expression of miR-378a-3p and miR-486-5p. There was no difference in prognosis in the 10 patients in the HLA-A*2402-unmatched group. Therefore, high miR-196b expression and low miR-378a-3p and miR-486-5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR-196b-5p, miR-378a-3p and miR-486-5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the association between tumor necrosis factor (TNF)-α polymorphisms and oral mucositis (OM) from 5-fluorouracil (5-FU) plus cisplatin (CDDP) chemotherapy for esophageal cancer. The rs1799964 polymorphism of TNF-α was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction. The experimental group comprised 64 patients who received chemotherapy for esophageal cancer between 1997 and 2004; a total of 106 patients between 2005 and 2013 were investigated as the validation group. Univariate analysis of the experimental group revealed that the TT genotype of TNF-α rs1799964 was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes [univariate odds ratio (OR)=4.0; P=0.029]. Similarly, univariate analysis of the validation group revealed that the percentage of the TT genotype was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes (OR=2.8; P=0.043). This difference in risk was replicated in the validation cohort. Thus, the TT genotype of TNF-α rs1799964 may be a predictor of chemotherapy-induced OM in patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

The aim of the present study was to characterize infiltrated T cell clones that define the tumor immune environment and are important in the response to treatment in patients with advanced colorectal cancer (CRC). In order to explore predictive biomarkers for the efficacy of immunochemotherapies, T cell receptor (TCR) repertoire analysis was performed using blood samples and tumor tissues obtained from patients with advanced CRC that had been treated with a combination of five-cancer peptide vaccines and oxaliplatin-based chemotherapy. The TCR-a/β complementary DNAs (cDNAs), prepared from the messenger RNAs (mRNAs) obtained from 17 tumor tissues and 39 peripheral blood mononuclear cells of 9 CRC patients at various time points, were sequenced. The oligoclonal enrichment of certain TCR sequences was identified in tumor tissues and blood samples; however, only a few TCR sequences with a frequency of >0.1% were commonly detected in pre- and post-treatment tumor tissues, or in post-treatment blood and tissue samples. The average correlation coefficients of the TCR-a and TCR-β clonotype frequencies between the post-treatment tumor tissues and blood samples were 0.023 and 0.035, respectively, and were much lower compared with the correlation coefficients of the TCR-a and TCR-β clonotype frequencies between pre- and post-treatment blood samples (0.430 and 0.370, respectively), suggesting that T cell populations in tumor tissues vary from those in blood. Although the sample size was small, a tendency for the TCR diversity in tumor tissues to drastically decrease during the treatment was indicated in two patients, who exhibited a longer progression-free survival time. The results of the present study suggest that TCR diversity scores in tissues may be a useful predictive biomarker for the therapeutic effect of immunochemotherapy for patients with advanced CRC. [ABSTRACT FROM AUTHOR]

Neoplastic cells that are exfoliated from the colorectal epithelium exhibit dysfunctional apoptotic mechanisms, and thus it is possible to identify high-molecular-weight DNA fragments (long DNA) in feces. In the present study, the sensitivity and specificity of fecal-based long DNA assays were evaluated for the detection of colorectal cancer (CRC). Feces were collected from 54 healthy volunteers and 130 patients with CRC prior to surgical treatment. The presence of long DNA of the adenomatosis polyposis coli, Kirsten rat sarcoma viral oncogene homolog (KRAS), B-raf proto-oncogene, serine/threonine kinase and p53 genes was assessed by polymerase chain reaction followed by electrophoresis. The identification of long DNA in feces was found to exhibit a sensitivity of 56.2% and specificity of 96.3% for CRC detection. In addition, long DNA was identified in the feces of 58/90 (64.4%) patients with distal CRC and 15/40 (37.5%) patients with proximal CRC. This study indicates the potential of the fecal long DNA assay as a non-invasive and easily performed method for the detection of individuals with CRC. [ABSTRACT FROM AUTHOR]