Improving the prediction accuracy in classification using the combined data sets by ranks of gene expressions

<p>Abstract</p> <p>Background</p> <p>The information from different data sets experimented under different conditions may be inconsistent even though they are performed with the same research objectives. More than that, even when the data sets were generated from the same platform, the data agreement may be affected by the technical variation among the laboratories. In this case, it is necessary to use the combined data set after adjusting the differences between such data sets, for detecting the more reliable information.</p> <p>Results</p> <p>The proposed method combines data sets posterior to the discretization of data sets based on the ranks of the gene expression ratios, and the statistical method is applied to the combined data set for predictive gene selection. The efficiency of the proposed method was evaluated using five colon cancer related data sets, which were experimented using cDNA microarrays with different RNA sources, and one experiment utilized oligonucleotide arrays. NCI-60 cell lines data sets were used, which were performed with two different platforms of cDNA microarrays and Affymetrix HU6800 oligonucleotide arrays. The combined data set by the proposed method predicted the test data sets more accurately than the separated data sets did. The biological significant genes were detected from the combined data set, which were missed on the separated data sets.</p> <p>Conclusion</p> <p>By transforming gene expressions using ranks, the proposed method is not influenced by systematic bias among chips and normalization method. The method may be especially more useful to find predictive genes from data sets which have different scale in gene expressions.</p

Novel and simple transformation algorithm for combining microarray data sets

<p>Abstract</p> <p>Background</p> <p>With microarray technology, variability in experimental environments such as RNA sources, microarray production, or the use of different platforms, can cause bias. Such systematic differences present a substantial obstacle to the analysis of microarray data, resulting in inconsistent and unreliable information. Therefore, one of the most pressing challenges in the field of microarray technology is how to integrate results from different microarray experiments or combine data sets prior to the specific analysis.</p> <p>Results</p> <p>Two microarray data sets based on a 17k cDNA microarray system were used, consisting of 82 normal colon mucosa and 72 colorectal cancer tissues. Each data set was prepared from either total RNA or amplified mRNA, and the difference of RNA source between these two data sets was detected by ANOVA (Analysis of variance) model. A simple integration method was introduced which was based on the distributions of gene expression ratios among different microarray data sets. The method transformed gene expression ratios into the form of a reference data set on a gene by gene basis. Hierarchical clustering analysis, density and box plots, and mixture scores with correlation coefficients revealed that the two data sets were well intermingled, indicating that the proposed method minimized the experimental bias. In addition, any RNA source effect was not detected by the proposed transformation method. In the mixed data set, two previously identified subgroups of normal and tumor were well separated, and the efficiency of integration was more prominent in tumor groups than normal groups. The transformation method was slightly more effective when a data set with strong homogeneity in the same experimental group was used as a reference data set.</p> <p>Conclusion</p> <p>Proposed method is simple but useful to combine several data sets from different experimental conditions. With this method, biologically useful information can be detectable by applying various analytic methods to the combined data set with increased sample size.</p

Genome-wide genetic aberrations of thymoma using cDNA microarray based comparative genomic hybridization

BACKGROUND: Thymoma is a heterogeneous group of tumors in biology and clinical behavior. Even though thymoma is divided into five subgroups following the World Health Organization classification, the nature of the disease is mixed within the subgroups. RESULTS: We investigated the molecular characteristics of genetic changes variation of thymoma using cDNA microarray based-comparative genomic hybridization (CGH) with a 17 K cDNA microarray in an indirect, sex-matched design. Genomic DNA from the paraffin embedded 39 thymoma tissues (A 6, AB 11, B1 7, B2 7, B3 8) labeled with Cy-3 was co-hybridized with the reference placenta gDNA labeled with Cy-5. Using the CAMVS software, we investigated the deletions on chromosomes 1, 2, 3, 4, 5, 6, 8, 12, 13 and 18 throughout the thymoma. Then, we evaluated the genetic variations of thymoma based on the subgroups and the clinical behavior. First, the 36 significant genes differentiating five subgroups were selected by Significance Analysis of Microarray. Based on these genes, type AB was suggested to be heterogeneous at the molecular level as well as histologically. Next, we observed that the thymoma was divided into A, B (1, 2) and B3 subgroups with 33 significant genes. In addition, we selected 70 genes differentiating types A and B3, which differ largely in clinical behaviors. Finally, the 11 heterogeneous AB subtypes were able to correctly assign into A and B (1, 2) types based on their genetic characteristics. CONCLUSION: In our study, we observed the genome-wide chromosomal aberrations of thymoma and identified significant gene sets with genetic variations related to thymoma subgroups, which might provide useful information for thymoma pathobiology.ope

Two Dosages of Oral Fluoropyrimidine S-1 of 35 and 40 mg/m2 bid: Comparison of the Pharmacokinetic Profiles in Korean Patients with Advanced Gastric Cancer

Objective: In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after adminis-tration of S-1 at 35 or 40 mg/m2 bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer. Methods: Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m2, ranging from 70 to 88 mg/m2. Results: Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. Cmax and AUC0–48h values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity. Conclusions: We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs. Key words: S-1 – gastric cancer – pharmacokinetics – Asian populatio

Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction

Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival

Relationship Between Sarcopenia and Prognosis in Patient With Concurrent Chemo-Radiation Therapy for Esophageal Cancer

Background: Sarcopenia, defined as skeletal muscle loss, has been known as a poor prognosis factor in various malignant diseases The aim of this study is to investigate the effect of sarcopenia on prognosis in patients with esophageal cancer who received concurrent chemo- and radiotherapy (CCRT).Methods: We retrospectively collected clinical data of 287 patients with esophageal cancer who were treated by definite CCRT at Gangnam Severance and Severance hospital from August 2005 to December 2014. The cross-sectional area of muscle at the level of the third lumbar vertebra was measured using pre- and post-CCRT computed tomography images. Sarcopenia was defined as skeletal muscle index &lt;49 cm2/m2 for men and of &lt;31 cm2/m2 for women by Korean-specific cutoffs. Overall survival (OS) and progression free survival (PFS) were analyzed according to sarcopenia.Results: Sarcopenia identified before CCRT did not affect OS and PFS. However, patients with post-CCRT sarcopenia showed shorter OS and PFS than patients without it (median OS: 73 months vs. 28 months; median PFS: 34 months vs. 25 months, respectively). Post-CCRT sarcopenia was an independent prognostic factor of poor OS (hazards ratio: 1.697; 95% confidence interval: 1.036–2.780; P = 0.036). In multivariate analysis, male sex (P = 0.004) and presence of CCRT-related complications, such as esophagitis or general weakness were significantly associated with post-CCRT sarcopenia (P = 0.016).Conclusions: Sarcopenia after CCRT can be a useful predictor for long-term prognosis in patients with esophageal cancer. To control CCRT-related complications may be important to prevent skeletal muscle loss during CCRT

Salvage chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) in previously treated patients with advanced gastric cancer

PURPOSE: This phase II trial first describes the combination chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) for pretreated advanced gastric cancer (AGC) patients. METHODS: Patients who had previously been treated with greater than or equal to one regimen were enrolled. They received S-1 35 mg/m(2) twice daily on days 1-14 and irinotecan 150 mg/m(2) on days 1 and 15, every 4 weeks. The primary endpoint was overall survival (OS). RESULTS: Among the 38 patients enrolled, 18 patients were treated as second line, and the remaining 20 patients were enrolled as third- or fourth line. A total of 208 cycles were administered with the median being four cycles (range 1-16). The median OS was 8.7 months [95% confidence interval (CI) 7.5-10.3], and the median progression-free survival was 6.3 months (95% CI 5.3-7.3). Low serum albumin (<3.5 mg/dL) was an independent adverse prognosticator for survival. Overall response rate was 17% (95% CI 4-30%). The major grade 3/4 toxicities were neutropenia (26%) and diarrhea (18%). CONCLUSIONS: Biweekly IRIS showed the moderate activity as salvage treatment in AGC. Considering high neutropenia and gastrointestinal toxicity, patient selection should be warranted; serum albumin may be a predictive factor for treatment decisionope