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Hierarchical Clustering Analysis (hierarchical + clustering_analysis)
Selected AbstractsGene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarraysLIVER TRANSPLANTATION, Issue 5 2009Naoki Hama Acute cellular rejection (ACR) is still a major problem in organ transplantation, and its genetic and molecular mechanisms remain poorly understood. We used DNA microarrays to investigate the gene expression profiles in ACR. We hypothesized that changes of gene expression in grafts could also be detected in peripheral blood leukocytes. We first compared the gene expression profiles in liver isografts (Lewis to Lewis) and allografts (Dark Agouti to Lewis) harvested from rats at days 1, 3, 5, and 7 after transplantation. Hierarchical clustering analysis indicated that gene expression started to change on day 3, and 89 differentially expressed genes were extracted from allografts in comparison with isografts at day 3. Most of the up-regulated genes were associated with graft-infiltrating leukocytes. We then confirmed the similarity of gene expression changes in peripheral leukocytes by quantitative real-time polymerase chain reaction. We also investigated the gene expression changes in other inflammatory and liver dysfunction models. Two interferon-gamma inducible genes, interferon regulatory factor 1 and guanylate nucleotide binding protein 2, were overexpressed in both the peripheral leukocytes and liver graft during ACR. Although further studies are necessary, these 2 genes in peripheral leukocytes could be potentially useful markers for rejection or immunosuppression. Liver Transpl 15:509,521, 2009. © 2009 AASLD. [source] Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysisPATHOLOGY INTERNATIONAL, Issue 12 2007Gehan Gamal To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%). The PAP-mixed was significantly male predominant and had more progressed clinicopathological features. A significant cytological difference was observed among the three subgroups. A tissue microarray was constructed and immunohistochemistry was undertaken using 15 biomarkers. Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters. The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups. Statistically, approximately half of the 15 biomarkers were significant for differentiating between ADMIX subgroups and between different histological growth patterns. In conclusion, ADMIX can be classified into three histopathological subgroups according to the most differentiated growth pattern, of which a PAP growth pattern might indicate more aggressive behavior than that of a BAC growth pattern. [source] Novel classification based on immunohistochemistry combined with hierarchical clustering analysis in non-functioning neuroendocrine tumor patientsCANCER SCIENCE, Issue 10 2010Shinya Iida Somatostatin analogues ameliorated many symptoms caused by neuroendocrine tumors (NET), but their antitumor activities are limited especially in non-functioning cases. An overactivation of signaling pathways under receptor tyrosine-kinase (RTK) has been recently demonstrated in some NET patients, but its details have remained largely unknown. Therefore, in this study, we immunolocalized therapeutic factors and evaluated the data to study the clinical significance of the molecules in non-functioning Japanese gastrointestinal NET. Fifty-two NET cases were available for examination in this study and expression of somatostatin receptor (sstr) 1, 2A, 2B, 3 and 5, activated form of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4-binding protein 1 (4EBP1), ribosomal protein s6 (S6), extracellular signal-regulated kinase (ERK) and insulin-like growth factor 1 receptor (IGF-1R) was evaluated using immunohistochemistry. We then studied the correlation among the immunohistochemical results of the individual cases using hierarchical clustering analysis. Results of clustering analysis demonstrated that NET cases were basically classified into Cluster I and II. Cluster I was associated with higher expression of sstr1, 2B and 3 and Cluster II was characterized by an activation of the PI3K/Akt pathway and IGF-1R and higher proliferative status. Cluster II was further classified into Cluster IIa and IIb. Cluster IIa was associated with higher expression of sstr1 and 5 and higher proliferative status and Cluster IIb was characterized by ERK activation. Hierarchical clustering analysis of immunoreactivity of the therapeutic factors can classify NET cases into three distinctive groups and the medical treatment may be determined according to this novel classification method for non-functioning NET patients. (Cancer Sci 2010; 00: 000,000) [source] Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expressionARTHRITIS & RHEUMATISM, Issue 3 2010Patricia J. Hunter Objective To identify biomarkers in the first synovial fluid (SF) aspirate obtained from children with oligoarticular juvenile idiopathic arthritis (JIA), which could be used to identify children whose disease is likely to extend to a more severe phenotype. Methods Patients with recent-onset oligoarticular JIA were identified and grouped according to those whose mild disease persisted (persistent disease) or those whose disease would extend from a mild to more severe phenotype (extended-to-be disease) at 1 year after diagnosis. Flow cytometry was used to delineate differences in the mononuclear cell populations between the first blood sample and first SF aspirate from the same patient and between outcome (persistent versus extended-to-be) groups. Proportions of lymphocytes in the joint were modeled on chemotaxis of lymphocytes to CCL5, using Transwell migration assays. Levels of CCL5 in the SF were quantified by enzyme-linked immunosorbent assay. RNA profiles of SF mononuclear cells were compared between groups using the Affymetrix GeneChip hybridization protocol and hierarchical clustering analyses. Results Compared with peripheral blood mononuclear cells, SF mononuclear cells displayed an expansion of CD8+ T cells, reduced proportion of B cells, and expansion of CD16, natural killer cells. The lower CD4:CD8 ratio in the SF was recapitulated in vitro by the observed migration of blood T cells in response to CCL5. Synovial CCL5 levels were higher in children whose disease extended to a more severe phenotype. The CD4:CD8 ratio in the SF was significantly lower in patients with extended-to-be oligoarticular JIA (0.57 compared with 0.90 in the persistent disease group, difference 0.33, 95% confidence interval 0.04,0.62; P = 0.009). Gene expression profiling revealed that 344 genes were >1.5-fold differentially expressed between outcome groups (P < 0.05), and these included genes associated with inflammation and macrophage differentiation, which showed increased levels in patients with extended disease at 1 year, and genes associated with immune regulation, which showed increased levels in patients with persistent disease at 1 year. Conclusion Analyses of the proportions of synovial lymphocytes, levels of CCL5, and differential gene expression yielded potential biomarkers with which to predict the likelihood of extension of oligoarticular JIA to a more severe disease phenotype. [source] Receptor architecture of human cingulate cortex: Evaluation of the four-region neurobiological modelHUMAN BRAIN MAPPING, Issue 8 2009Nicola Palomero-Gallagher Abstract The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABAB, benzodiazepine, and M3 but lower NMDA and GABAA binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, ,2, 5-HT1A, and D1 but lowest GABAA densities. The MCC has lowest AMPA, kainate, ,2, and D1 densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABAA, GABAB, and M2 receptors. The PCC and RSC differ in the higher M1 and ,1 but lower M3 densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profilesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Ayodele A. Alaiya Abstract Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors. © 2002 Wiley-Liss, Inc. [source] Endomyocardial biopsy derived adherent proliferating cells,A potential cell source for cardiac tissue engineeringJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Marion Haag Abstract Heart diseases are a leading cause of morbidity and mortality. Cardiac stem cells (CSC) are considered as candidates for cardiac-directed cell therapies. However, clinical translation is hampered since their isolation and expansion is complex. We describe a population of human cardiac derived adherent proliferating (CAP) cells that can be reliably and efficiently isolated and expanded from endomyocardial biopsies (0.1,cm3). Growth kinetics revealed a mean cell doubling time of 49.9,h and a high number of 2.54,×,107 cells in passage 3. Microarray analysis directed at investigating the gene expression profile of human CAP cells demonstrated the absence of the hematopoietic cell markers CD34 and CD45, and of CD90, which is expressed on mesenchymal stem cells (MSC) and fibroblasts. These data were confirmed by flow cytometry analysis. CAP cells could not be differentiated into adipocytes, osteoblasts, chondrocytes, or myoblasts, demonstrating the absence of multilineage potential. Moreover, despite the expression of heart muscle markers like ,-sarcomeric actin and cardiac myosin, CAP cells cannot be differentiated into cardiomyocytes. Regarding functionality, CAP cells were especially positive for many genes involved in angiogenesis like angiopoietin-1, VEGF, KDR, and neuropilins. Globally, principal component and hierarchical clustering analysis and comparison with microarray data from many undifferentiated and differentiated reference cell types, revealed a unique identity of CAP cells. In conclusion, we have identified a unique cardiac tissue derived cell type that can be isolated and expanded from endomyocardial biopsies and which presents a potential cell source for cardiac repair. Results indicate that these cells rather support angiogenesis than cardiomyocyte differentiation. J. Cell. Biochem. 109: 564,575, 2010. © 2009 Wiley-Liss, Inc. [source] Quantitative analysis and chromatographic fingerprinting for the quality evaluation of Forsythia suspensa extract by HPLC coupled with photodiode array detectorJOURNAL OF SEPARATION SCIENCE, JSS, Issue 23-24 2009Yonggang Xia Abstract A simple and reproducible HPLC-photodiode array detector method has been described for evaluating and controlling quality of Forsythia suspensa extract (FSE). First, by analysis of chromatographic fingerprints, the similarities of chromatograms of FSE samples from the same pharmaceutical company exceeded 0.999, 0.997 and 0.960, respectively, although they were much lower from different pharmaceutical companies. Second, by further comparing many batches of extract chromatograph charts with the corresponding reference herb materials, the "common peaks" 3, 5, 7 and 10 were defined as "marker peaks", which were identified as (+)-pinoresinol-,- D -glucoside, forsythiaside, phillyrin and phillygenin, respectively. Third, four "marker peaks" were simultaneously determined based on fingerprint chromatogram for further controlling the quality of FSE quantitatively. Namely, the newly developed method was successfully applied to analyze 38 batches of FSE samples supplied by three pharmaceutical factories, which showed acceptable linearity, intra-day precision (RSD<2.76%), inter-day precision (RSD<3.43%) and the average recovery rates in the range of (95.38±2.96)% to (101.60±3.08)%. At last, hierarchical clustering analysis and Bayes discriminant analysis statistical methods were used to classify and differentiate the 38 FSE samples to provide the basis for guiding reasonable use of FSE and controlling its quality better. [source] Fingerprint chromatogram analysis of Pseudostellaria heterophylla (Miq.) Pax root by high performance liquid chromatographyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 14 2006Chao Han Abstract A simple and reliable high performance liquid chromatographic (HPLC) method has been developed and validated for the fingerprinting of extracts from the root of Pseudostellaria heterophylla (Miq.) Pax. HPLC with gradient elution was performed on an authentic reference standard of powdered P. heterophylla (Miq.) Pax root and 11 plant samples of the root were collected from different geographic locations. The HPLC chromatograms have been standardized through the selection and identification of reference peaks and the normalization of retention times and peak intensities of all the common peaks. The standardized HPLC fingerprints show high stability and reproducibility, and thus can be used effectively for the screening analysis or quality assessment of the root or its derived products. Similarity index calculations based on cosine angle values or correlation methods have been performed on the HPLC fingerprints. As a group, the fingerprints of the P. heterophylla (Miq.) Pax samples studied are highly correlated with closely similar fingerprints. Within the group, the samples can be further divided into subgroups based on hierarchical clustering analysis (HCA). Sample grouping based on HCA coincides nicely with those based on the geographical origins of the samples. The HPLC fingerprinting techniques thus have high potential in authentication or source-tracing types of applications. [source] Analysis of query keywords of sports-related queries using visualization and clusteringJOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY, Issue 8 2009Jin Zhang The authors investigated 11 sports-related query keywords extracted from a public search engine query log to better understand sports-related information seeking on the Internet. After the query log contents were cleaned and query data were parsed, popular sports-related keywords were identified, along with frequently co-occurring query terms associated with the identified keywords. Relationships among each sports-related focus keyword and its related keywords were characterized and grouped using multidimensional scaling (MDS) in combination with traditional hierarchical clustering methods. The two approaches were synthesized in a visual context by highlighting the results of the hierarchical clustering analysis in the visual MDS configuration. Important events, people, subjects, merchandise, and so on related to a sport were illustrated, and relationships among the sports were analyzed. A small-scale comparative study of sports searches with and without term assistance was conducted. Searches that used search term assistance by relying on previous query term relationships outperformed the searches without the search term assistance. The findings of this study provide insights into sports information seeking behavior on the Internet. The developed method also may be applied to other query log subject areas. [source] Identification of tryptase- and chymase-related gene clusters in human mast cells using microarraysALLERGY, Issue 3 2006C. Dahl Tryptase and chymase are the two major granular proteases present in human mast cell (MC)s. We used oligonucleotide microarray to measure the levels of approximately 22 000 transcripts in cord blood-derived MCs at 4 weeks, 8 weeks, 12 weeks and 18 weeks in culture. Tryptase (TPSB2) was expressed at the highest level among all transcripts and its expression level reached a plateau at 8 weeks. On the other hand, the expression level of chymase (CMAI) doubled every 4,6 weeks. A similar tendency was found at the protein levels with FACS analysis. After filtering the transcripts with MC-specificity, hierarchical clustering analysis identified 494 and 81 transcripts in the same clusters with tryptase and chymase, respectively. MC-specific genes, KIT and HDC were found in the tryptase cluster. In the chymase cluster, a critical suppressor for cell senescence, BMI1 and the several related genes were found, suggesting that chymase expression may be closely related to cell senescence/quiescence events. [source] IgA nephropathy and mesangial cell proliferation: shared global gene expression profilesNEPHROLOGY, Issue 2002Hideto SAKAI SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [,- 33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN. [source] The effects of MRI signal intensity changes and clinical manifestations on prognosis after surgical intervention for cervical spondylotic myelopathyORTHOPAEDIC SURGERY, Issue 2 2009Ying-ze Zhang MD Objective:, To investigate whether the magnetic resonance (MR) T2 image signal intensity ratio and clinical manifestations can predict the prognosis in patients with cervical spondylotic myelopathy (CSM). Methods:, A total of 73 patients treated with anterior, posterior, or posterior-anterior combined surgery for compressive cervical myelopathy were enrolled retrospectively in this study. 1.5 T magnetic resonance imaging (MRI) was performed on all patients before surgery. T2-weighted images (T2WI) of sagittal signal intensity were obtained of the cervical spinal cord, and the regions of interest (ROI) were taken by 0.05 cm2. MR T2WI of sagittal normal cord signal at the C7-T1 disc level were also obtained, and the ROI were taken by 0.3 cm2. Signal value was measured by computer and the signal ratio between regions 0.05 cm2 and 0.3 cm2 calculated. Where no intramedullary high signal intensity was noted on MR T2WI, the ROI were taken by 0.05 cm2 of the region of most severe spinal cord compression. The 73 patients were divided into three groups by hierarchical clustering analysis with signal intensity ratio (group 1: low signal intensity ratio; group 2: middle signal intensity ratio; group 3: high signal intensity ratio). Statistical analyses were performed with SPSS 11.0. Results:, There were significant differences between the three groups according to the recovery rate (P < 0.001), age (P= 0.003), duration of disease (P= 0.001), Babinski sign (P < 0.001), pre- and postoperative Japanese Orthopaedic Association (JOA) score (P= 0.006). With increases in both signal intensity ratio grade and age, the recovery rate and pre- and postoperative JOA scores gradually decreased, and the incidence of Babinski sign increased. There was no significant difference in sex among the three groups (P= 0.387). Multiple comparison tests further supported the above-mentioned results. Conclusion:, Patients with light or no intramedullary signal changes on T2WI had a good surgical outcome. However, increase of signal intensity ratio and occurrence of the pyramidal sign were associated with a poor prognosis after surgery. [source] Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysisPATHOLOGY INTERNATIONAL, Issue 12 2007Gehan Gamal To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%). The PAP-mixed was significantly male predominant and had more progressed clinicopathological features. A significant cytological difference was observed among the three subgroups. A tissue microarray was constructed and immunohistochemistry was undertaken using 15 biomarkers. Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters. The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups. Statistically, approximately half of the 15 biomarkers were significant for differentiating between ADMIX subgroups and between different histological growth patterns. In conclusion, ADMIX can be classified into three histopathological subgroups according to the most differentiated growth pattern, of which a PAP growth pattern might indicate more aggressive behavior than that of a BAC growth pattern. [source] Plant-extract-induced changes in the proteome of the soil-borne pathogenic fungus Thielaviopsis basicolaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2010Joėlle V. F. Coumans Abstract Thielaviopsis basicola is a hemibiotroph fungus that causes black root rot disease in diverse plants with significant impact on cotton production in Australia. To elucidate how T. basicola growth and proteome are influenced by interactions with natural sources, this fungus was cultured in the presence of root extracts from non-host (wheat, hairy vetch) and susceptible host (cotton, lupin) plants. We found that T. basicola growth was significantly favored in the presence of host extracts, while hierarchical clustering analysis of 2-DE protein profiles of T. basicola showed plant species had a larger effect on the proteome than host/non-host status. Analysis by LC-MS/MS of unique and differentially expressed spots and identification using cross-species similarity searching and de novo sequencing allowed successful identification of 41 spots. These proteins were principally involved in primary metabolism with smaller numbers implicated in other diverse functions. Identification of several "morpho" proteins suggested morphological differences that were further microscopically investigated. Identification of several highly expressed spots suggested that vitamin B6 is important in the T. basicola response to components present in hairy vetch extract, and finally, three spots, induced in the presence of lupin extract, may correspond to malic enzyme and be involved in lipid accumulation. [source] Novel classification based on immunohistochemistry combined with hierarchical clustering analysis in non-functioning neuroendocrine tumor patientsCANCER SCIENCE, Issue 10 2010Shinya Iida Somatostatin analogues ameliorated many symptoms caused by neuroendocrine tumors (NET), but their antitumor activities are limited especially in non-functioning cases. An overactivation of signaling pathways under receptor tyrosine-kinase (RTK) has been recently demonstrated in some NET patients, but its details have remained largely unknown. Therefore, in this study, we immunolocalized therapeutic factors and evaluated the data to study the clinical significance of the molecules in non-functioning Japanese gastrointestinal NET. Fifty-two NET cases were available for examination in this study and expression of somatostatin receptor (sstr) 1, 2A, 2B, 3 and 5, activated form of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4-binding protein 1 (4EBP1), ribosomal protein s6 (S6), extracellular signal-regulated kinase (ERK) and insulin-like growth factor 1 receptor (IGF-1R) was evaluated using immunohistochemistry. We then studied the correlation among the immunohistochemical results of the individual cases using hierarchical clustering analysis. Results of clustering analysis demonstrated that NET cases were basically classified into Cluster I and II. Cluster I was associated with higher expression of sstr1, 2B and 3 and Cluster II was characterized by an activation of the PI3K/Akt pathway and IGF-1R and higher proliferative status. Cluster II was further classified into Cluster IIa and IIb. Cluster IIa was associated with higher expression of sstr1 and 5 and higher proliferative status and Cluster IIb was characterized by ERK activation. Hierarchical clustering analysis of immunoreactivity of the therapeutic factors can classify NET cases into three distinctive groups and the medical treatment may be determined according to this novel classification method for non-functioning NET patients. (Cancer Sci 2010; 00: 000,000) [source] Prediction of in vitro response to interferon-, in renal cell carcinoma cell linesCANCER SCIENCE, Issue 4 2007Toru Shimazui We analyzed the correlation between interferon-, (IFN,) response and gene expression profiles to predict IFN, sensitivity and identified key molecules regulating the IFN, response in renal cell carcinoma (RCC) cell lines. To classify eight RCC cell lines of the SKRC series into three subgroups according to IFN, sensitivity, that is, sensitive, resistant and intermediate group, responses to IFN, (300,3000 IU/mL) were quantified by WST-1 assay. Microarray, followed by supervised hierarchical clustering analysis, was applied to selected genes according to IFN, sensitivity. In order to find alteration of expression profiles induced by IFN,, sequential microarray analyses were performed at 3, 6, and 12 h after IFN, treatment of RCC cell lines and mRNA expression level was confirmed using quantitative real time polymerase chain reaction. According to the sequential microarray analysis between IFN,-sensitive and -resistant line, seven genes were selected as candidates for IFN,-sensitivity-related genes in RCC cell lines. Among these seven genes, we further developed a model to predict tumor inhibition with four genes, that is, adipose differentiation-related protein, microphthalmia associated transcription factor, mitochondrial tumor suppressor 1, and troponin T1 using multiple linear regression analysis (coefficient = 0.948, P = 0.0291) and validated the model using other RCC cell lines including six primary cultured RCC cells. The expression levels of the combined selected genes may provide predictive information on the IFN, response in RCC. Furthermore, the IFN, response to RCC might be modulated by regulation of the expression level of these molecules. (Cancer Sci 2007; 98: 529,534) [source] | ||||||||||||||||