scholarly journals Roles of G1 cyclins in the temporal organization of yeast cell cycle - a transcriptome-wide analysis

2018 ◽  
Author(s):  
Lotte Teufel ◽  
Katja Tummler ◽  
Max Flöttmann ◽  
Andreas Herrmann ◽  
Naama Barkai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Expression Profiles ◽  
Temporal Organization ◽  
Fine Tuning ◽  
Peak Time ◽  
Time Resolved ◽  
G1 Cyclins ◽  
Measured Time ◽  
Cell Cycle Phases

AbstractOscillating gene expression is crucial for correct timing and progression through cell cycle. In Saccharomyces cerevisiae, G1 cyclins Cln1-3 are essential drivers of the cell cycle and have an important role for temporal fine-tuning. We measured time-resolved transcriptome-wide gene expression for wild type and cyclin single and double knockouts over cell cycle with and without osmotic stress. Clustering of expression profiles, peak-time detection of oscillating genes, integration with transcription factor network dynamics, and assignment to cell cycle phases allowed us to quantify the effect of genetic or stress perturbations on the duration of cell cycle phases. Cln1 and Cln2 showed functional differences, especially affecting later phases. Deletion of Cln3 led to a delay of START followed by normal progression through later phases. Our data and network analysis suggest mutual effects of cyclins with the transcriptional regulators SBF and MBF.

scholarly journals Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression

2019 ◽  
Vol 116 (39) ◽  
pp. 19490-19499 ◽  
Author(s):  
Chenglong Xia ◽  
Jean Fan ◽  
George Emanuel ◽  
Junjie Hao ◽  
Xiaowei Zhuang
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Spatial Information ◽  
Detection Efficiency ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Rna Profiling ◽  
Spatially Resolved ◽  
Cycle Dependent

The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluorescence in situ hybridization (MERFISH) has achieved spatially resolved RNA quantification at transcriptome scale by massively multiplexing single-molecule FISH measurements. Here, we increased the gene throughput of MERFISH and demonstrated simultaneous measurements of RNA transcripts from ∼10,000 genes in individual cells with ∼80% detection efficiency and ∼4% misidentification rate. We combined MERFISH with cellular structure imaging to determine subcellular compartmentalization of RNAs. We validated this approach by showing enrichment of secretome transcripts at the endoplasmic reticulum, and further revealed enrichment of long noncoding RNAs, RNAs with retained introns, and a subgroup of protein-coding mRNAs in the cell nucleus. Leveraging spatially resolved RNA profiling, we developed an approach to determine RNA velocity in situ using the balance of nuclear versus cytoplasmic RNA counts. We applied this approach to infer pseudotime ordering of cells and identified cells at different cell-cycle states, revealing ∼1,600 genes with putative cell cycle-dependent expression and a gradual transcription profile change as cells progress through cell-cycle stages. Our analysis further revealed cell cycle-dependent and cell cycle-independent spatial heterogeneity of transcriptionally distinct cells. We envision that the ability to perform spatially resolved, genome-wide RNA profiling with high detection efficiency and accuracy by MERFISH could help address a wide array of questions ranging from the regulation of gene expression in cells to the development of cell fate and organization in tissues.

345 GENE EXPRESSION IN OOCYTES AFTER MEIOTIC INHIBITION WITH THE CYCLIN-DEPENDENT KINASE INHIBITOR BUTYROLACTONE I

2010 ◽  
Vol 22 (1) ◽  
pp. 329
Author(s):  
C. L. V. Leal ◽  
S. Mamo ◽  
T. Fair ◽  
P. Lonergan
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Relative Abundance ◽  
Kinase Inhibitor ◽  
Expression Profiles ◽  
Cyclin Dependent Kinase ◽  
Oocyte Competence ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Bovine Oocytes

Once removed from the follicle, mammalian oocytes resume meiosis spontaneously and progress through breakdown of the germinal vesicle to the matured state at metaphase II. The ability to reversibly inhibit such meiotic resumption has been reported and is a potentially useful method for studying developmental competence acquisition in oocytes as well as in some cases allowing flexibility in an IVF system where oocytes are collected from distant locations or on different days. The aim of the present study was to determine the effect of temporary inhibition of meiotic resumption using the cyclin-dependent kinase inhibitor butyrolactone I (BLI) on gene expression in bovine oocytes. Immature bovine oocytes were recovered from the ovaries of slaughtered heifers at a commercial abattoir and assigned to 1 of 4 groups: (1) Control: immature oocytes were collected either immediately or (2) after IVM for 24 h in TCM-199 containing 10 ng mL-1 EGF and 10% (v/v) FCS, (3) Inhibited oocytes collected either 24 h after incubation in the presence of 100 μM BLI in TCM-199 with 3 mg mL-1 BSA or (4) after meiotic inhibition for 24 h followed by in vitro maturation. All cultures were carried out at 38.5°C under 5% CO2 in air and maximum humidity. For mRNA relative abundance analysis, cumulus cells were removed and pools of 10 denuded oocytes were snap frozen in liquid nitrogen and stored at -80°C until use. A total of 42 transcripts, previously reported to be related to cell cycle regulation and/or oocyte competence were evaluated by quantitative real time PCR. Differences in relative abundance were analyzed by ANOVA and Student’s t-test. The majority of transcripts were downregulated (P < 0.05) after IVM in control oocytes (23 out of 42) and the same pattern was observed in inhibited oocytes that were allowed to mature. Twelve transcripts remained stable (P > 0.05) after IVM in control oocytes; of these, only two (PTTG1 and INHBA) did not show the same pattern in inhibited and matured oocytes. Few genes (7) were upregulated after IVM in control oocytes (P < 0.05) and of these, three (PLAT1, RBP1, and INHBB) were not upregulated in inhibited oocytes after IVM. Inhibited oocytes showed similar levels of expression (P > 0.05) as immature control oocytes, except for two genes (LUM and INHBB), which were increased in these oocytes (P < 0.05). The expression profiles of cell cycle genes were mostly unaffected by the BLI treatment. The few genes affected were previously reported as competence-related and could be useful markers of oocyte competence following pretreatment. In conclusion, the changes occurring in transcript abundance during oocyte maturation in vitro were to a large extent mirrored following inhibition of meiotic resumption prior to IVM and subsequent release from inhibition and maturation. CLV Leal was supported by CNPq, Brazil (PDE 201487/2007-1); Supported by Science Foundation Ireland (07/SRC/B1156).

Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4998-5006 ◽  
Author(s):  
Florence Magrangeas ◽  
Valéry Nasser ◽  
Hervé Avet-Loiseau ◽  
Béatrice Loriod ◽  
Olivier Decaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
Immune Response ◽  
Light Chain ◽  
Dna Microarrays ◽  
Chromosomal Abnormalities ◽  
Expression Profiles ◽  
Cell Cycle Control ◽  
Primary Tumors

AbstractAlthough multiple myeloma (MM) is a unique entity, a marked heterogeneity is actually observed among the patients, which has been first related to immunoglobulin (Ig) types and light chain subtypes and more recently to chromosomal abnormalities. To further investigate this genetic heterogeneity, we analyzed gene expression profiles of 92 primary tumors according to their Ig types and light chain subtypes with DNA microarrays. Several clusters of genes involved in various biologic functions such as immune response, cell cycle control, signaling, apoptosis, cell adhesion, and structure significantly discriminated IgA- from IgG-MM. Genes associated with inhibition of differentiation and apoptosis induction were up-regulated while genes associated with immune response, cell cycle control, and apoptosis were down-regulated in IgA-MM. According to the expression of the 61 most discriminating genes, BJ-MM represented a separate subgroup that did not express either the genes characteristic of IgG-MM or those of IgA-MM at a high level. This suggests that transcriptional programs associated to the switch could be maintained up to plasma cell differentiation. Several genes whose products are known to stimulate bone remodeling discriminate between κ- and λ-MM. One of these genes, Mip-1α, was overexpressed in the κ subgroup. In addition, we established a strong association (P = .0001) between κ subgroup expressing high levels of Mip-1α and active myeloma bone disease. This study shows that DNA microarrays enable us to perform a molecular dissection of the bioclinical diversity of MM and provide new molecular tools to investigate the pathogenesis of malignant plasma cells.

The IGF1-R Inhibitor AEW541 Is a Potent Anti-Myeloma Agent That Overcomes Drugs Resistance, and Has Synergistic Activity with Other New Drugs.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2599-2599
Author(s):  
Patricia Maiso ◽  
Enrique M. Ocio ◽  
Mercedes Garayoa ◽  
Mark A. Pearson ◽  
Atanasio Pandiella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
Expression Profiles ◽  
Chemotherapeutic Agents ◽  
Mitochondrial Outer Membrane ◽  
Late Time ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Myeloma Cells

Abstract Multiple myeloma (MM) represents an incurable disease for which development of new therapies is required. Here we report the effect on myeloma cells of AEW541, a new small molecule, belonging to the pyrrolo[2,3-d] pyrimidine class, identified as inhibitor of the IGF-1R in vitro kinase activity. AEW541 showed a potent antimyeloma activity (IC50 <4.5 μM) on MM cell lines both sensitive (MM1S, U266, OPM2, RPMI8226) and resistant (MM1R and U266LR7) to conventional chemotherapeutic agents. In fresh cells from five MM patients a marked antitumor activity was confirmed. AEW541 showed a synergistic effect with dexamethasone and lenalidomide, while it was additive with melphalan and bortezomib. Moreover the triple combination of AEW541, bortezomib and dexamethasone showed even higher anti-MM activity. Gene expression profiles of MM1S cells identified a total of 967 genes to be significantly deregulated (transcriptional changes in gene expression of 2-fold or greater) by treatment with AEW541. The classification of these genes according to functional categories indicated that 3.5% were involved in apoptosis/responses to stress and 13% in the control of cell cycle/proliferation. By Western analyses, we observed that AEW541 affected genes involved in cell cycle and cell death pathways. AEW541 blocked cell cycle progression, and this was accompanied by p27, up-regulation and pRb, CCND1, CCNA and CCNE downregulation. AEW541 induced cell death through an increase in the mitochondrial outer membrane permeability and provoked DNA fragmentation. AEW541 induced apoptosis and at late time points, also activated caspases 8,9 and 3. The pan-caspase inhibitor Z-VAD-FMK only slightly decreased the sensitivity to AEW541. In addition, AEW541 stimulated a caspase-independent pathway, through the release of AIF and Endonuclease G from the mitochondria. It is therefore conceivable that both caspase dependent and independent pathways are activated by AEW541 in MM cells, although the effect of AEW541 on cell cycle arrest is an earlier and more potent event. Finally, AEW541 was able to overcome the protective effect that confers IL-6, IGF-1 and BMSCs to myeloma cells in a dose dependent manner. All these data indicate that AEW541 could be a useful drug for the treatment of MM patients, particularly in combination with other novel agents such as bortezomib or lenalidomide together with dexamethasone.

Hematopoiesis in the Elderly: Age-Associated Effects in Frequency, Function, and Gene Expression of Human Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1505-1505
Author(s):  
Wendy W. Pang ◽  
Elizabeth A. Price ◽  
Irving L. Weissman ◽  
Stanley L. Schrier
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Expression Profiles ◽  
Frequency Function ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Cell Cycle Status

Abstract Abstract 1505 Poster Board I-528 Aging of the human hematopoietic system is associated with an increase in the development of anemia, myeloid malignancies, and decreased adaptive immune function. While the hematopoietic stem cell (HSC) population in mouse has been shown to change both quantitatively as well as functionally with age, age-associated alterations in the human HSC and progenitor cell populations have not been characterized. In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated and compared HSC and other hematopoietic progenitor populations prospectively isolated via fluorescence activated cell sorting (FACS) from 10 healthy young (20-35 years of age) and 8 healthy elderly (65+ years of age) human bone marrow samples. Bone marrow was obtained from hematologically normal young and old volunteers, under a protocol approved by the Stanford Institutional Review Board. We determined by flow cytometry the distribution frequencies and cell cycle status of HSC and progenitor populations. We also analyzed the in vitro function and generated gene expression profiles of the sorted HSC and progenitor populations. We found that bone marrow samples obtained from normal elderly adults contain ∼2-3 times the frequency of immunophenotypic HSC (Lin-CD34+CD38-CD90+) compared to bone marrow obtained from normal young adults (p < 0.02). Furthermore, upon evaluation of cell cycle status using RNA (Pyronin-Y) and DNA (Hoechst 33342) dyes, we observed that a greater percentage of HSC from young bone marrow are in the quiescent G0- phase of the cell cycle compared to elderly HSC, of which there is a greater percentage in G1-, S-, G2-, or M-phases of the cell cycle (2.5-fold difference; p < 0.03). In contrast to the increase in HSC frequency, we did not detect any significant differences in the frequency of the earliest immunophenotypic common myeloid progenitors (CMP; Lin-CD34+CD38+CD123+CD45RA-), granulocyte-macrophage progenitors (GMP; Lin-CD34+CD38+CD123+CD45RA+), and megakaryocytic-erythroid progenitors (MEP; Lin-CD34+CD38+CD123-CD45RA-) from young and elderly bone marrow. We next analyzed the ability of young and elderly HSC to differentiate into myeloid and lymphoid lineages in vitro. We found that elderly HSC exhibit diminished capacity to differentiate into lymphoid B-lineage cells in the AC6.21 culture environment. We did not, however, observe significant differences in the ability of young and elderly HSC to form myeloid and erythroid colonies in methylcellulose culture, indicating that myelo-erythroid differentiation capacity is preserved in elderly HSC. Correspondingly, gene expression profiling of young and elderly human HSC indicate that elderly HSC have up-regulation of genes that specify myelo-erythroid fate and function and down-regulation of genes associated with lymphopoiesis. Additionally, elderly HSC exhibit increased levels of transcripts associated with transcription, active cell-cycle, cell growth and proliferation, and cell death. These data suggest that hematopoietic aging is associated with intrinsic changes in the gene expression of human HSC that reflect the quantitative and functional alterations of HSC seen in elderly bone marrow. In aged individuals, HSC are more numerous and, as a population, are more myeloid biased than young HSC, which are more balanced in lymphoid and myeloid potential. We are currently investigating the causes of and mechanisms behind these highly specific age-associated changes in human HSC. Disclosures: Weissman: Amgen: Equity Ownership; Cellerant Inc.: ; Stem Cells Inc.: ; U.S. Patent Application 11/528,890 entitled “Methods for Diagnosing and Evaluating Treatment of Blood Disorders.”: Patents & Royalties.

Complete Response to First-Line Bortezomib-Thalidomide-Dexamethasone Therapy in Multiple Myeloma Patients with t(4;14): Analysis of Gene Expression Profile.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2811-2811
Author(s):  
Carolina Terragna ◽  
Sandra Durante ◽  
Daniel Remondini ◽  
Giovanni Martinelli ◽  
Francesca Patriarca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Cycle Progression ◽  
Plasma Cells ◽  
Expression Profiles ◽  
First Line ◽  
Cycle Progression ◽  
Hedgehog Signalling ◽  
Regulated Expression

Abstract Abstract 2811 Poster Board II-787 Introduction The recurrent translocation t(4;14)(p16;q32) occurs in less than 20% of patients with newly diagnosed Multiple Myeloma (MM) and is associated with a poor clinical outcome following either conventional or high-dose chemotherapy. Recently, it has been reported that patients carrying t(4;14) are prognostically heterogeneous and that the novel agents bortezomib and lenalidomide may overcome the poor prognosis related to this cytogenetic abnormality. In the present study, we analyzed the gene expression profile of patients who carried or not t(4;14) and were primarily treated with a bortezomib-based regimen. Patients and methods Two hundred thirty six patients with MM who received a combination of bortezomib-thalidomide-dexamethasone (VTD) as first-line therapy were evaluated for the presence at diagnosis of t(4;14). Of these, 41 patients (17.3%) were t(4;14) positive. On an intention-to-treat basis, the rate of CR and near CR (nCR) to VTD induction therapy among patients carrying t(4;14) was 41%, a value higher than the 29% observed among t(4;14) negative patients. In 218 patients for whom data on t(4;14), del(13q) and del(17p) were available, the differential gene expression of CD138+ enriched plasma cells was evaluated by means of expression microarray using the Affymetrix platform. The analysis was performed in t(4;14) negative patients and patients carrying t(4;14), either alone or combined with other abnormalities; t(4;14) negative patients included those with del(13q) alone and with any of these abnormalities. Results In 27 patients, t(4;14) was associated with either del(13q) (24 patients) or del(17p) (3 patients); the remaining 14 patients carried t(4;14) alone. The expression profiles of patients carrying either t(4;14) alone or t(4;14) combined with del(13q) significantly clustered apart when compared with those of cytogenetic negative patients. Similarly, the expression profiles of patients with del(13) alone clustered with those of cytogenetic negative patients. De-regulated expression of similar molecular pathways was demonstrated in patients carrying t(4;14) alone or combined with del(13q). Thus, the analysis of gene expression profiles according to response or no response to VTD was performed in two subgroups of patients, including those carrying t(4;14) alone or combined with del(13q) and those carrying either del(13q) alone or without cytogenetic abnormalities. By comparing the lists of genes differentially expressed (P '0.05) in patients who responded (e.g. those who achieved CR+nCR) and failed to respond (NR) to VTD according to the presence or absence of t(4;14), we found that the differential expression of 3719 genes characterized CR+nCR vs NR patients in the t(4;14) positive subgroup. At the opposite, the differential expression of 3182 genes characterized CR+nCR vs NR patients in the t(4;14) negative subgroup. 271 genes which were common to the two groups of genes were excluded from the list of genes found to be differentially expressed in t(4;14) positive patients who responded to VTD. Among these patients, we observed the de-regulated expression of genes involved in cell cycle progression (e.g. MDM2, CDK6 and SMAD2), Wnt signalling pathway (e.g. FZD7, WNT10A, MMP7,WNT2B, WNT6, WNT9A and DAAM2), and Hedgehog signalling pathway (GAS1, STK36 and GLI1). Overall, genes involved in cell cycle progression resulted over-expressed, thus suggesting a more aggressive phenotype of t(4;14) positive plasma cells of responder patients; nevertheless, the overall down-regulation of genes involved in Wnt and Hedgehog signalling pathways (known to be involved in the maintenance of a putative tumoral stem cell compartment) might mitigate this phenotype and predispose t(4;14) positive plasma cells to more favourably respond to VTD induction therapy. Supported by: BolognAIL, Fondazione Carisbo, Progetto di Ricerca Finalizzata (M.C). Disclosures: No relevant conflicts of interest to declare.

Gene Expression Profiles of Hydroxyurea Tolerant Cell Lines Identify Genetic Mechanisms That Influence Hydroxyurea Maximum Tolerated Dose

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1005-1005
Author(s):  
Rosa Diaz ◽  
Jonathan M Flanagan ◽  
Thad A Howard ◽  
Russell E. Ware
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Lines ◽  
Expression Profiles ◽  
K562 Cells ◽  
Maximum Tolerated Dose ◽  
False Discovery ◽  
Microarray Expression ◽  
Tolerant Cell

Abstract Abstract 1005 Hydroxyurea has emerged over the past decade as an effective therapeutic agent for patients with sickle cell anemia (SCA). However, drug dosing and hematological responses can be highly variable; both %HbF response and maximum tolerated dose (MTD) vary widely among patients with SCA who receive hydroxyurea treatment. To obtain further insight into the cellular and molecular pathways, as well as genetic factors that might influence the hydroxyurea MTD, K562 erythroleukemia cells were exposed to hydroxyurea in vitro, to create cell lines that were highly drug tolerant to doses ranging from 250μM to 1500μM. Cell lines had dose-response curves that exhibited clear drug tolerance; naïve K562 showed 50% proliferation in the presence of 250μM hydroxyurea, while tolerant cell lines showed >90% proliferation at the same dose as measured by the BrdU Cell Proliferation Assay. In addition, the tolerant lines showed normal and equivalent progression through cell cycle by flow cytometry cell cycle analysis. After 15 weeks of continuous exposure, cells were harvested and mRNA microarray expression profiles were analyzed for naïve K562 (no hydroxyurea exposure) and cell lines tolerant to 500, 1000, or 1500μM hydroxyurea. Gene expression was measured on Affymetrix U133 Plus 2.0 chips. Differential expression between sample groups was determined using ANOVA, and p-values were corrected for multiple testing using the Benjamin-Hochberg false discovery rate (FDR) method to identify genetic profiles and genes consistently increased or decreased compared to naïve K562 cells. Using a threshold of 2-fold change compared to untreated cells and a false discovery rate <5%, a total of 864 genes were significantly altered in hydroxyurea tolerant cells, including 337 genes whose expression consistently correlated with increasing hydroxyurea dose (Pearson correlation p<.001). The PANTHER classification system was used to group genes into categories based on molecular functions. Of the genes that correlated significantly with increasing hydroxyurea dosing (n=337), there were 181 up-regulated genes and 156 down-regulated genes that had molecular functions including catalytic activity, binding, transcription regulator activity and transporter activity. Genes with transporter activity included SLC6A19, ATP6VOD1, ABCG2, ATP6V1B2 and KCNN4. Other genes of interest based on function included RRM2, PLS3, KCNAB2, UBE2A and SRI. Real-time quantitative reverse transcription (RT)-PCR then quantified the expression of 20 candidate genes to verify the accuracy of the microarray expression data. The next steps will include correlation of these findings with clinical data, specifically early reticulocyte mRNA expression and hydroxyurea MTD values obtained from children with SCA enrolled in the prospective Hydroxyurea Study of Long-term Effects (HUSTLE, NCT00305175). These data document that continuous in vitro exposure of K562 cells to hydroxyurea leads to tolerant cell lines that feature substantial changes in gene expression. Altered expression of certain genes present in erythroid cells including RRM2 and membrane transporters represent compensatory changes in response to hydroxyurea exposure, and may help explain the variability in hydroxyurea MTD observed among patients with SCA. Disclosures: Off Label Use: Hydroxyurea is not FDA approved for pediatric sickle cell patients. Howard:Baylor College of Medicine: Employment.

scholarly journals Integrated bioinformatics analysis reveals ASPM and CENPF with prognostic value in lung cancer

2019 ◽  
Author(s):  
jinghang li ◽  
Jing Zhang ◽  
Lin Huang ◽  
Sheng Zhao
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Cycle ◽  
Expression Profiles ◽  
Mirna Gene ◽  
Gene Expression Profiles ◽  
Genetic Alterations ◽  
Potential Candidate ◽  
Expression Microarrays ◽  
Regulation Of Cell Cycle

Abstract Lung cancer (LC) is the most frequent type of cancer in the world. But the mechanism of LC is still largely unknown. In this study, we analyzed three lung cancer gene expression microarrays of different pathologic types to explore the potential candidate genes in LC by Integrated bioinformatical methods. 459 overlapped differentially expressed genes (DEGs) were explored in three GEO gene expression profiles of different pathologic types of lung cancer and function annotation of DEGs were performed. The main biological process of DEGs was regulation of vasculature development and angiogenesis. The most significant molecular function of DEGs was TGF-β receptor activity. The most significant Reactome pathway of DEGs was cell cycle and extracellular matrix organization pathway. The PPI network of the DEGs was constructed and 23 candidate hub genes were identified in the network . Kaplan-Meier survival analysis show 21 genes were associated with the prognosis of LC. The genetic alterations analysis of these genes by using cBioPortal shown ASPM has the highest genetic alteration rate of 9% in main pathological types of 3191 LC patients , CENPF has the second highest alteration rate of 6% in LC patients. ASPM and CENPF also identified have a significant co-occurrence relationship in LC, and the GO analysis shown they both participate in the regulation of cell cycle. In the TF -miRNA-gene network of 21 genes shown CENPF have the most significant value in the network and the most relevant TF are NFYA, E2F1 and MYC.In conclusion, this study explored several key genes about LC and analyzed potential TF of those genes, provides possible therapeutic targets and biomarker for further clinical application.

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