scholarly journals Identification of Pan-Cancer Biomarkers Based on the Gene Expression Profiles of Cancer Cell Lines

2021 ◽  
Vol 9 ◽  
Author(s):  
ShiJian Ding ◽  
Hao Li ◽  
Yu-Hang Zhang ◽  
XianChao Zhou ◽  
KaiYan Feng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Feature Selection ◽  
Cell Line ◽  
Cancer Patients ◽  
Cell Lines ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Biomarkers ◽  
Cancer Types ◽  
Pan Cancer

There are many types of cancers. Although they share some hallmarks, such as proliferation and metastasis, they are still very different from many perspectives. They grow on different organ or tissues. Does each cancer have a unique gene expression pattern that makes it different from other cancer types? After the Cancer Genome Atlas (TCGA) project, there are more and more pan-cancer studies. Researchers want to get robust gene expression signature from pan-cancer patients. But there is large variance in cancer patients due to heterogeneity. To get robust results, the sample size will be too large to recruit. In this study, we tried another approach to get robust pan-cancer biomarkers by using the cell line data to reduce the variance. We applied several advanced computational methods to analyze the Cancer Cell Line Encyclopedia (CCLE) gene expression profiles which included 988 cell lines from 20 cancer types. Two feature selection methods, including Boruta, and max-relevance and min-redundancy methods, were applied to the cell line gene expression data one by one, generating a feature list. Such list was fed into incremental feature selection method, incorporating one classification algorithm, to extract biomarkers, construct optimal classifiers and decision rules. The optimal classifiers provided good performance, which can be useful tools to identify cell lines from different cancer types, whereas the biomarkers (e.g. NCKAP1, TNFRSF12A, LAMB2, FKBP9, PFN2, TOM1L1) and rules identified in this work may provide a meaningful and precise reference for differentiating multiple types of cancer and contribute to the personalized treatment of tumors.

Melphalan Resistance in Multiple Myeloma Can Be Overcome by Proteasome Inhibition or Histone Deacetylation: Lack of Syngergism of the Combination.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3393-3393
Author(s):  
Pieter Sonneveld ◽  
Eric Kamst ◽  
Yvonne de Knegt ◽  
Naomi Klarenbeek ◽  
Martijn Schoester
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Cell Line ◽  
Cell Lines ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Proteasome Inhibition ◽  
Histone Deacetylation ◽  
Interaction Factor ◽  
Resistant Cells

Abstract Multiple Myeloma (MM) is a disease of monoclonal plasma cells in the bone marrow which has a transient response to classic chemotherapy. At diagnosis, induction chemotherapy followed by high-dose melphalan (HDM) with stem cell support is used in most patients to achieve a clinical response. Because all patients will ultimately relapse, the treatment of melphalan-refractory disease represents a major clinical challenge and new agents are needed to overcome melphalan resistance. We have investigated the anti-myeloma efficacy of two new classes of targeted agents, i.e. proteasome inhibition and histone deacetylation inhibition alone or in combination in the melphalan sensitive MM1S and the Melphalan refractory MM1MEL2000 cell lines. The IC50 values of Bortezomib (B), Melphalan (M) and LAQ824 (L) in MM1S were 2.1 nM, 1.9 uM and 1.7 nM, respectively and in MM1MEL2000 3.9 nM, 50 uM and 4.0 nM. Using isobologram analysis a synergysm between B and L was observed in the sensitive, however not in the melphalan refractory cell line. These data indicate that B proteasome inhibition and histone deacetylation inhibition may be effective ways to overcome melphalan resistance. However, the previously reported synergism between these drugs does not seem to occur in melphalan resistant cells. The gene expression profiles of these cell lines were analysed using the Affymetrix U133plus 2.0 gene chip before and after treatment with melfaphalan or the proteasome inhibitor B or the histone deacetylation inhibitor L or the combination of B and L. Genes that were highly expressed in the melphalan refractory derivate cell line MM1MEL2000 as compared with wild-type MM1S included GP M6B, ADAM23 and HTPAP. Following melphalan exposure, TMF1, a CEBp glucocorticoid interaction factor, WHSC1L1, a MMSET homologue with EGF like domain and several transcription factors had highly increased expression as compared to MM1S. With exposure to B combined with L, increased expression in MM1MEL2000 over MM1S was observed for GTP exchange factor TIAM1 which interacts with RAS and JNK, and the lymphoid enhancer factor, a notch transcription factor. It is concluded that Bortezomib and the histone deacetylase inhibitor LAQ824 are effective agents to overcome melphalan resistance in multiple myeloma. However, the combination fails to show the synergism observed in melphalan sensitive cells. Gene analysis sofar does not provide a clear explanation for this lack of synergism. A comprehensive summary of the observed shifts of gene expression profiles in melphalan resistant cells following exposure to these agents, will be presented.

Metabolic evaluation of sporadic papillary kidney cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 377-377
Author(s):  
Brian Shuch ◽  
Christopher Ricketts ◽  
Carole Sourbier ◽  
Shinji Tsutsumi ◽  
Xiu-ying Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Membrane Potential ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Kidney Cancer ◽  
Expression Profiles ◽  
Fumarate Hydratase ◽  
Gene Expression Profiles ◽  
Cancer Cell Lines

377 Background: Papillary kidney cancer, which occurs in 15% of patients with kidney cancer, can be aggressive and there is currently no effective form of therapy for this disease. To evaluate the metabolic characteristics of sporadic papillary kidney cancer, we have evaluated metabolic parameters of several papillary kidney cancer cell lines and available gene expression profiles. Methods: Established cell lines derived from patients with sporadic papillary kidney cancer (LABAZ, MDACC-55, HRC-86T2) and from a hereditary form of fumarate hydratase-deficient kidney cancer (UOK262) were evaluated. All sporadic lines were initially sequenced for fumarate hydratase (FH). All cell lines were metabolically profiled using the Seahorse Extracellular Flux Analyzer and further evaluated for reactive oxygen species (ROS), mitochondrial membrane potential, and glucose dependence. Finally gene expression profiles of publically available datasets of papillary and HLRCC tumors were downloaded, normalized, and analyzed. Results: Sporadic lines had no alterations in FH and metabolic analysis demonstrated normal oxygen consumption and minimal lactate production, in contrast to highly glycolytic UOK262. Also unlike UOK262, the sporadic papillary kidney cancer lines were not sensitive to glucose withdrawal, had low levels of ROS, and had normal mitochondria membrane potential. Principal component analysis (PCA) demonstrated that HLRCC tumor specimens are very different from sporadic papillary tumors at the molecular level. Conclusions: Our study of established sporadic papillary RCC and fumarate hydratase-deficient HLRCC cell line together with analysis of available gene expression profiles demonstrates that these sporadic papillary kidney cancer cell lines appear to have a distinct metabolic profile from those in the fumarate hydratase deficient kidney cancer cell line. Understanding the metabolic basis of papillary kidney cancer could provide the foundation for the development of targeted approaches to therapy for patients with this disease.

scholarly journals Gene expression profiles of liver cancer cell lines reveal two hepatocyte-like and fibroblast-like clusters

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245939
Author(s):  
Keita Fukuyama ◽  
Masataka Asagiri ◽  
Masahiro Sugimoto ◽  
Hiraki Tsushima ◽  
Satoru Seo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Cell Lines ◽  
Liver Cancer Cell ◽  
Study Objective

Cancer cell lines are widely used in basic research to study cancer development, growth, invasion, or metastasis. They are also used for the development and screening of anticancer drugs. However, there are no clear criteria for choosing the most suitable cell lines among the wide variety of cancer cell lines commercially available for research, and the choice is often based on previously published reports. Here, we investigated the characteristics of liver cancer cell lines by analyzing the gene expression data available in the Cancer Cell Line Encyclopedia. Unsupervised clustering analysis of 28 liver cancer cell lines yielded two main clusters. One cluster showed a gene expression pattern similar to that of hepatocytes, and the other showed a pattern similar to that of fibroblasts. Analysis of hepatocellular carcinoma gene expression profiles available in The Cancer Genome Atlas showed that the gene expression patterns in most hepatoma tissues were similar to those in the hepatocyte-like cluster. With respect to liver cancer research, our findings may be useful for selecting an appropriate cell line for a specific study objective. Furthermore, our approach of utilizing a public database for comparing the properties of cell lines could be an attractive cell line selection strategy that can be applied to other fields of research.

scholarly journals Molecular Characterization of Putative Chordoma Cell Lines

Sarcoma ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Silke Brüderlein ◽  
Joshua B. Sommer ◽  
Paul S. Meltzer ◽  
Sufeng Li ◽  
Takuya Osada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Cell Lines ◽  
Copy Number ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Cancer Cell Line ◽  
Copy Number Variations ◽  
Genetic Changes

Immortal tumor cell lines are an important model system for cancer research, however, misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in detail. We analyzed gene expression patterns and genomic copy number variations in five putative chordoma cell lines (U-CH1, CCL3, CCL4, GB60, and CM319). We also created a new chordoma cell line, U-CH2, and provided genotypes for cell lines for identity confirmation. Our analyses revealed that CCL3, CCL4, and GB60 are not chordoma cell lines, and that CM319 is a cancer cell line possibly derived from chordoma, but lacking expression of key chordoma biomarkers. U-CH1 and U-CH2 both have gene expression profiles, copy number aberrations, and morphology consistent with chordoma tumors. These cell lines also harbor genetic changes, such as loss of p16, MTAP, or PTEN, that make them potentially useful models for studying mechanisms of chordoma pathogenesis and for evaluating targeted therapies.

scholarly journals Different gene expression profiles of AD293 and HEK293 cell lines that show contrasting susceptibility to apoptosis induced by overexpression of Bim L.

2006 ◽  
Vol 53 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Jiayi Zhang ◽  
Jinzhong Chen ◽  
Lingfeng Liu ◽  
Chaoneng Ji ◽  
Shaohua Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Cell Lines ◽  
Expression Profile ◽  
Hek293 Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Subtractive Hybridization ◽  
Hek293 Cells ◽  
Differential Expression Profile

Bim is a pro-apoptotic member of the Bcl-2 protein family. Overexpression of Bim proved to be highly cytotoxic for diverse cells. The AD293 cell line is derived directly from the HEK293 cell line but has been transfected with a gene that can improve cell adherence. We found that there was almost no apoptosis seen in Bim L-transfected AD293 cells, but more than half of Bim L-transfected HEK293 cells underwent apoptosis. Suppression subtractive hybridization was used to detect the different gene expression profile between these two cell lines. In 192 sequenced positive clones, there were 30 clones repeating twice or more. Ten genes were selected for identification by semi-quantitative RT-PCR. The transcripts of two adhesion-related genes (actin and parvin) and two apoptosis-related genes (cyclin 2 and protein phosphatase 1G) were up-regulated in AD293 cells. These results suggest that the high expression of cell adhesion-related proteins might be responsible for the different apoptosis status after the transfection of Bim L. Our data provide candidate genes responsible for the different apoptosis sensitivity of these two cell lines. Further investigation on the differential expression profile between AD293 and HEK293 might improve our understanding of cell apoptosis mechanism.

scholarly journals Pan-Cancer Transcriptional Models Predicting Chemosensitivity in Human Tumors

2021 ◽  
Vol 20 ◽  
pp. 117693512110024
Author(s):  
Jason D Wells ◽  
Jacqueline R Griffin ◽  
Todd W Miller
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Human Tumors ◽  
Molecular Characteristics ◽  
Survival Times ◽  
Chemotherapy Drugs ◽  
Testing Dataset ◽  
Cancer Models ◽  
Cancer Types ◽  
Pan Cancer

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

scholarly journals Genome-Wide Role of HSF1 in Transcriptional Regulation of Desiccation Tolerance in the Anhydrobiotic Cell Line, Pv11

2021 ◽  
Vol 22 (11) ◽  
pp. 5798
Author(s):  
Shoko Tokumoto ◽  
Yugo Miyata ◽  
Ruslan Deviatiiarov ◽  
Takahiro G. Yamada ◽  
Yusuke Hiki ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Desiccation Tolerance ◽  
Expression Profiles ◽  
Insect Cell Line ◽  
Gene Expression Profiles ◽  
Late Embryogenesis Abundant ◽  
Heat Shock Factor 1 ◽  
Genome Wide ◽  
A Genome

The Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of extreme hypometabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. The HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an extreme hypometabolism state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

scholarly journals Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines

Oncogene ◽  
2002 ◽  
Vol 21 (42) ◽  
pp. 6549-6556 ◽  
Author(s):  
Jiafu Ji ◽  
Xin Chen ◽  
Suet Yi Leung ◽  
Jen-Tsan A Chi ◽  
Kent Man Chu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Comprehensive Analysis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cell Lines

Design, synthesis, molecular docking and ADME studies of novel indole-thiazolidinedione derivatives and their antineoplastic activity as CDK6 inhibitors

2021 ◽  
Author(s):  
Zeynep Ates-Alagoz ◽  
Mehmet Murat Kisla ◽  
Fikriye Zengin Karadayi ◽  
Sercan Baran ◽  
Tuğba Somay Doğan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Antineoplastic Activity ◽  
Design Synthesis ◽  
Mcf 7

Several indole-thiazolidinedione derivatives (9–24) were designed and synthesized as CDK6 inhibitors, and their anticancer activity was probed on the MCF-7 cell line and the effects on gene expression profiles were elucidated.

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