Comprehensive Gene Expression Analysis Research Articles

Transcriptome Analysis in Male Strobilus Induction by Gibberellin Treatment in Cryptomeria japonica D. Don

The plant hormone gibberellin (GA) is known to regulate elongating growth, seed germination, and the initiation of flower bud formation, and it has been postulated that GAs originally had functions in reproductive processes. Studies on the mechanism of induction of flowering by GA have been performed in Arabidopsis and other model plants. In coniferous trees, reproductive organ induction by GAs is known to occur, but there are few reports on the molecular mechanism in this system. To clarify the gene expression dynamics of the GA induction of the male strobilus in Cryptomeria japonica, we performed comprehensive gene expression analysis using a microarray. A GA-treated group and a nontreated group were allowed to set, and individual trees were sampled over a 6-week time course. A total of 881 genes exhibiting changed expression was identified. In the GA-treated group, genes related to ‘stress response’ and to ‘cell wall’ were initially enriched, and genes related to ‘transcription’ and ‘transcription factor activity’ were enriched at later stages. This analysis also clarified the dynamics of the expression of genes related to GA signaling transduction following GA treatment, permitting us to compare and contrast with the expression dynamics of genes implicated in signal transduction responses to other plant hormones. These results suggested that various plant hormones have complex influences on the male strobilus induction. Additionally, principal component analysis (PCA) using expression patterns of the genes that exhibited sequence similarity with flower bud or floral organ formation-related genes of Arabidopsis was performed. PCA suggested that gene expression leading to male strobilus formation in C. japonica became conspicuous within one week of GA treatment. Together, these findings help to clarify the evolution of the mechanism of induction of reproductive organs by GA.

2059-P: Gene Repression during Maturation of Pancreatic ß-Cells Mirrors Those Upregulated in Islets of Diabetic db/db Mice

Pancreatic β-cells are specialized to properly regulate glucose metabolism. Loss of individual transcription factors that are critical for endocrine differentiation embryonically causes a deep loss of cell identity and upregulation of genes normally repressed in mature β-cells. We hypothesized that the factors important for maintenance of mature β-cell homeostasis are those that are lost in the identity loss or dedifferentiation. To identify genes critical for acquisition and loss of β-cell identity, we examined islets and β-cells by comprehensive gene expression analyses. Islets isolated from 8 wk (mature) and 4 wk (immature) old C57BL/6J mice were analyzed by microarray, and FACS-sorted mature β-cells (Mafa+7AAD-) and other islet cells including Mafa negative β-cells (Mafa-7AAD-) purified from Mafa reporter mice by RNAseq. We found that the maturation process involved genome-wide downregulated gene expression. Mature islets and Mafa+ β-cells had suppression of many genes including “β-cell disallowed genes” such as Igfbp4 and Nfib, but little to noupregulation of genes critical for β-cell function such as Ins1, Slc2a2, Ucn3 and Sytl4 from 4 wk to 8 wk. In contrast, most of the suppressed genes were significantly upregulated (by RNAseq) in islets from 21 wk old diabetic BKS-db/db mice compared with BKS-db/+ (misty). Comprehensive methylation screening (MeDIP-seq) of DNA from islets of 4 and 8 wk old C57BL/6J mice specifically identified highly methylated regulatory regions in some “repressed” genes in 8 wk old islets. In conclusion, the gain of identity during maturation phase of β-cells mirrors that of the dedifferentiation during diabetes. Disclosure W. Nishimura: None. M. Tumurkhuu: None. Y. Noda: None. K. Yasuda: None. Funding Japan Society for the Promotion of Science (JP16H01647, JP26461351, JP17K09843); International University of Health and Welfare; Japan Diabetes Foundation; Novartis Pharmaceuticals

Comprehensive Analysis of PD-1 Gene Expression, Immune Characteristics and Prognostic Significance in 1396 Glioma Patients.

BackgroundProgrammed cell death protein-1 (PD-1) blockade therapy is one of the most remarkable immunotherapy strategies in many solid tumors, excluding glioma. The PD-1 expression, immune characteristics, and prognosis relevance in glioma remain poorly understood.Patients and MethodsRNA sequencing (RNA-seq) and mRNA microarray data were obtained for 325 and 301 glioma patients, respectively, from the Chinese Glioma Genome Atlas (CGGA) database. We analyzed the expression profile of PDCD1 (encoding PD-1) according to the different grade, isocitrate dehydrogenase (IDH) mutation status, and molecular subtype of glioblastoma. Gene ontology (GO) analyses were performed to explore biological processes of PD-1-related genes. Survival analysis was conducted using the Kaplan–Meier method. The findings were validated using The Cancer Genome Atlas (TCGA) RNA-seq data from 697 glioma samples. We also confirmed the PDCD1 gene expression feature and survival relevance in our own cohort of 73 glioma patients. R language was used for statistical analysis and generating figures.ResultsPDCD1 was enriched in glioblastoma (WHO, grade IV), IDH wild-type glioma and mesenchymal glioblastoma in CGGA and TCGA datasets; similar results were validated in our own patient cohort. GO analysis revealed that PDCD1-related genes were involved in inflammation immune responses and T cell-mediated immune responses in glioma. Circos plots indicated that PDCD1 was positively associated with CD28, ICOS, and the inhibitory checkpoint molecules CTLA4, HAVCR2, TIGIT, and LAG3. Patients with PDCD1 upregulation had much shorter overall survival.ConclusionPDCD1 upregulation was found in more malignant phenotypes of glioma and indicated a worse prognosis. Immunotherapy of targeting PD-1 or combined with other checkpoint molecules (eg, TIM-3, LAG-3, or TIGIT) blockade may represent a promising treatment strategy for glioma.

Pyruvate-triggered TCA cycle regulation in Staphylococcus aureus promotes tolerance to betamethasone valerate

Staphylococcus aureus is a resident skin bacterium involved in the exacerbation of atopic dermatitis. Here we report that S. aureus regulates the tricarboxylic acid (TCA) cycle via the production of pyruvate for tolerance to betamethasone valerate (BV), an anti-inflammatory drug used in the treatment of atopic dermatitis. The addition of BV or clobetasol propionate to the medium among 5 different anti-inflammatory steroids delayed the growth of S. aureus. Comprehensive gene expression analysis by RNA-seq revealed that BV increased the expression of genes related to glycolysis in S. aureus. Pyruvate, a product of glycolysis, suppressed the S. aureus growth inhibition by BV. The addition of oxaloacetate, a compound in the TCA cycle biosynthesized from pyruvate, was also suppressed the inhibitory effect of BV. Malonate, an inhibitor of succinate dehydrogenase in the TCA cycle, increased the inhibitory effect of BV on the growth of S. aureus. These findings suggest that S. aureus promotes tolerance to BV, an anti-inflammatory steroid, by regulating the TCA cycle via the production of pyruvate.

12P Gene expression profiling in early breast cancer treated with neoadjuvant ribociclib plus letrozole (R+L) versus chemotherapy (CT): A correlative analysis of the SOLTI-1402/CORALLEEN phase II trial

In the CORALLEEN trial, R+L achieved similar response rates to multi-agent CT. We present a comprehensive gene expression analysis done before, during, and after therapy to fully characterize the biology behind the primary results of the trial.

Notch signaling is activated in knee-innervating dorsal root ganglia in an osteoarthritis mouse model

Purpose: Surgical destabilization of the medial meniscus (DMM) is a widely used mouse model to study the onset and progression of posttraumatic osteoarthritis (OA) and OA-associated pain. To explore peripheral neuronal mechanisms of OA pain, we used transcriptome microarrays to perform comprehensive gene expression analysis of knee-innervating dorsal root ganglia (L3-L5 DRG) after DMM surgery. We found that, in addition to known genes related to OA pain (including Ccl2, Cx3cl1, and Ngf), a number of genes encoding molecules in the Notch signaling pathway were regulated (mostly at late stage of disease, i.e.

Comprehensive Gene Expression Analysis and Identification of Stat-1 as Master Regulator in Oral Squamous Cell Carcinoma

Comprehensive Gene Expression Analysis and Identification of Stat-1 as Master Regulator in Oral Squamous Cell Carcinoma

Prediction of S-1 adjuvant chemotherapy benefit in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis.

Studies to identify predictive biomarkers of adjuvant chemotherapy with S-1 after gastrectomy in Stage II/III gastric cancer patients have been done; however, more clarity and understanding are needed. Our aim in the present study was to identify biomarkers predicting benefit due to S-1 adjuvant chemotherapy using comprehensive gene expression analysis. We retrospectively analyzed 102 patients receiving adjuvant chemotherapy with S-1 and 46 patients not receiving S-1 adjuvant chemotherapy after gastrectomy for gastric cancer treatment between January 2014 and December 2016. Hierarchical clustering analysis was performed based on the gene expression data obtained using cDNA microarray. Differentially expressed genes (DEGs) were identified using thresholds of absolute fold changes of > 4.0 and a false discovery rate P value of < 0.01. Gene Ontology (GO) analysis and GO network visualization were performed using the ClueGO app in Cytoscape. Hierarchical clustering analysis in patients treated with S-1 adjuvant chemotherapy revealed two clusters with favorable and unfavorable survival outcomes. We identified 147 upregulated DEGs and 192 downregulated DEGs in the favorable outcome group. GO analysis to identify significantly upregulated genes showed enrichment in immune-related genes and GO terms. Upregulation of these immune-related genes was not associated with survival in patients not receiving S-1 adjuvant chemotherapy. The upregulation and enrichment of immune-related genes and GO terms may be predictive biomarkers in patients who would benefit from adjuvant S-1 chemotherapy to treat Stage II/III gastric cancer.

Aberrant expression of Wnt/β-catenin signaling pathway genes in aggressive malignant gastric gastrointestinal stromal tumors

IntroductionRecent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis. Materials and methodsWe investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands. ResultsGEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7. ConclusionWnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST.

Role of plasminogen activator inhibitor-1 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells

There is increasing evidence that epithelial-mesenchymal transition (EMT) contributes to the development of organ fibrosis. We demonstrated that methotrexate (MTX) clearly induced EMT through the transforming growth factor (TGF)-β-related signaling pathway in human alveolar epithelial cell line, A549. However, critical factors associated with MTX-induced EMT have not yet been identified. In our study, we attempted to identify factors playing a crucial role in MTX-induced EMT in A549 cells. We focused on plasminogen activator inhibitor-1 (PAI-1) as the possible target for the prevention of MTX-induced EMT-related lung injury. Comprehensive gene expression analysis by microarray revealed that mRNA expression level of PAI-1 was clearly increased by MTX treatment. In addition, using several cloned A549 cells, we found a good correlation between MTX-induced increase in mRNA expression levels of α-smooth muscle actin (SMA), a representative EMT marker, and PAI-1. Furthermore, MTX upregulated mRNA and protein expression levels of PAI-1 in A549 cells; this upregulation was canceled by co-treatment with SB431542, a TGF-β-related signaling pathway inhibitor. Notably, tiplaxtinin, a PAI-1 inhibitor, and knockdown of urokinase-type plasminogen activator receptor (uPAR) prevented MTX-induced EMT in A549 cells. These findings indicate that MTX may induce EMT via upregulation of PAI-1 expression and interaction of PAI-1 with uPAR in A549 cells.

Comprehensive analysis of DNA methylation and gene expression in orally tolerized T cells

T cell anergy is known to be a crucial mechanism for various types of immune tolerance, including oral tolerance. The expression of several anergy-specific genes was reportedly up-regulated in anergic T cells, and played important roles in the cells. However, how the genes were up-regulated has not been understood. In this study, we comprehensively analyzed the altered gene expression and DNA methylation status in T cells tolerized by oral antigen in vivo. Our results showed that many genes were significantly up-regulated in the orally tolerized T cells, and most of the genes found in this study have not been reported previously as anergy related genes; for example, ribosomal protein L41 (FC = 3.54E06, p = 3.70E-09: Fisher's exact test; the same applies hereinafter) and CD52 (FC = 2.18E05, p = 3.44E-06). Furthermore, we showed that the DNA methylation statuses of many genes; for example, enoyl-coenzyme A delta isomerase 3 (FC = 3.62E-01, p = 3.01E-02) and leucine zipper protein 1 (FC = 4.80E-01, p = 3.25E-02), including the ones distinctly expressed in tolerized T cells; for example, latexin (FC = 3.85E03, p = 4.06E-02 for expression; FC = 7.75E-01, p = 4.13E-01 for DNA methylation) and small nuclear ribonucleoprotein polypeptide F (FC = 3.12E04, p = 4.46E-04 for expression; FC = 8.56E-01, p = 5.15E-01 for DNA methylation), changed during tolerization, suggesting that the distinct expression of some genes was epigenetically regulated in the tolerized T cells. This study would contribute to providing a novel clue to the fine understanding of the mechanism for T cell anergy and oral tolerance.

Phenotypic traits and gonadal development of hybrids between Misgurnus anguillicaudatus and Paramisgurnus dabryanus

Misgurnus anguillicaudatus and Paramisgurnus dabryanus are two loach species widely sympatrically distributed in China. Hybrids of the two species have been detected in the wild and produced by artificial hybridization experiments, but their sexual development has not been studied. In this study, the phenotypic traits of purebred and hybrid groups were evaluated in the aspects of survival, growth, gonad development and sex-related genes (dmrt1a, dmrt1b, cyp19a1a and cyp19a1b) expression. Hybrids and purebreds showed the same high levels of fertilization, hatching success and early survival. Growth of hybrids was intermediate between those of parental species, showing hybrid heterosis compared to M. anguillicaudatus. Cyp19a1a and dmrt1s were expressed in the ovary and testis but expression levels were sexually dimorphic. Although the exact timing of dmrt1s and cyp19a1a expression during the gonad development varied between groups, in general their expressions were correlated with the differentiation and formation of testes and ovaries respectively. Histological analysis showed that in purebreds ovaries differentiate/form much earlier than testes: 15/35 and 35/80 days after hatching (dah) respectively. In hybrids, however, both differentiation and formation are simultaneous: 35 and 80 dah respectively. Adult hybrids possessed mature gametes, but they appeared to exhibit weaker reproductive ability than either of the parental species. Comprehensive gene expression and histological analysis demonstrate that gonad development in hybrids is retarded than in parental species.

Comprehensive gene expression analysis after ERH gene knockdown in human bladder cancer T24 cell lines

In this article, we utilized Ingenuity® Pathway Analysis (IPA®) bioinformatics analysis software and Metascape® bioinformatics analysis website tools to analyse the possible mechanism of ERH affecting tumourigenesis (proliferation and apoptosis) in bladder cancer (BC) T24 cells. The ERH gene was knocked down, and BC T24 cells were divided into ERH normal and knockdown groups. Affymetrix® gene expression microarrays were performed to obtain a differentially expressed gene list (DEGL) between the 2 groups. IPA® data analyses contain five modules: disease and function analysis, upstream analysis, regulator effects analysis, canonical pathway analysis and molecular network analysis. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were analysed by Metascape®. The results of the gene expression profiling chip and the DEGL showed that 344 genes were upregulated and 254 genes were downregulated. The IPA® and Metascape® pathway analyses showed that the ERH gene may affect proliferation and apoptosis by affecting the apoptosis, cell cycle, Toll-like receptor (TLR), NF-κB or TGF-beta signalling pathways. Upstream analysis determined that the ERH gene may regulate TNF and NK-κB in the BC T24 cell lines. The ERH gene may be involved in the "cell death and survival" molecular network in BC T24 cells. ERH may be a regulator of KITLG through TNF. The ERH gene may affect apoptosis through the TLR, NF-κB, TNF or TGF-beta signalling pathways in BC T24 cells, and may be a regulator of KITLG to ultimately activate the growth of malignant tumours.

Postweaning Iron Deficiency in Male Rats Leads to Long-Term Hyperactivity and Decreased Reelin Gene Expression in the Nucleus Accumbens

Background:Epidemiological research indicates that iron deficiency (ID) in infancy correlates with long-term cognitive impairment and behavioral disturbances, despite therapy. However, the mechanisms underlying these effects are unknown. Objectives:We investigated how ID affected postweaning behavior and monoamine concentration in rat brains to determine whether ID during the juvenile period affected gene expression and synapse formation in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Methods:Fischer 344/Jcl postweaning male rats aged 21–39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. After day 39, all rats were fed the iron-adequate diet. The locomotor activity was evaluated by the open field and elevated plus maze tests at 8 and 12 wk of age. Monoamine concentrations in the brain were analyzed using HPLC at 9 and 13 wk of age. Comprehensive gene expression analysis was performed in the PFC and NAcc at 13 wk of age. Finally, we investigated synaptic density in the PFC and NAcc by synaptophysin immunostaining. Results:Behavioral tests revealed a significant reduction of the age-related decline in the total distance traveled in ID rats compared with CN rats (P < 0.05), indicating that ID affected hyperactivity, which persisted into adulthood (13 wk ofage). At this age, reelin (Reln) mRNA expression (adjusted P < 0.01) decreased and synaptic density (P < 0.01) increasedin the NAcc in the ID group. Regarding the mesolimbic pathway, homovanillic acid concentration increased in the NAcc,whereas the dopamine concentration decreased in the ventral midbrain. Conclusions:Our results suggest that ID during the postweaning period in male rats, despite complete iron repletion following ID, led to long-term hyperactivity via monoamine disturbance in the brain and an alteration in the synaptic plasticity accompanied by downregulation of Reln expression in the NAcc.

Comprehensive Analysis of Differential Gene Expression to Identify Common Gene Signatures in Multiple Cancers.

BackgroundWith the development of research on cancer genomics and microenvironment, a new era of oncology focusing on the complicated gene regulation of pan-cancer research and cancer immunotherapy is emerging. This study aimed to identify the common gene expression characteristics of multiple cancers – lung cancer, liver cancer, kidney cancer, cervical cancer, and breast cancer – and the potential therapeutic targets in public databases.Material/MethodsGene expression analysis of GSE42568, GSE19188, GSE121248, GSE63514, and GSE66272 in the GEO database of multitype cancers revealed differentially expressed genes (DEGs). Then, GO analysis, KEGG function, and path enrichment analyses were performed. Hub-genes were identified by using the degree of association of protein interaction networks. Moreover, the expression of hub-genes in cancers was verified, and hub-gene-related survival analysis was conducted. Finally, infiltration levels of tumor immune cells with related genes were explored.ResultsWe found 12 cross DEGs in the 5 databases (screening conditions: “adj p<0.05” and “logFC>2 or logFC<–2”). The biological processes of DEGs were mainly concentrated in cell division, regulation of chromosome segregation, nuclear division, cell cycle checkpoint, and mitotic nuclear division. Furthermore, 10 hub-genes were obtained using Cytoscape: TOP2A, ECT2, RRM2, ANLN, NEK2, ASPM, BUB1B, CDK1, DTL, and PRC1. The high expression levels of the 10 genes were associated with the poor survival of these multiple cancers, as well as ASPM, may be associated with immune cell infiltration.ConclusionsAnalysis of the common DEGs of multiple cancers showed that 10 hub-genes, especially ASPM and CDK1, can become potential therapeutic targets. This study can serve as a reference to understand the characteristics of different cancers, design basket clinical trials, and create personalized treatments.

Study Protocol for Pleiotropic Effects and Safety of Sodium-Glucose Cotransporter2 Inhibitor Versus Sulfonylurea in Patients with Type2 Diabetes and Nonalcoholic Fatty Liver Disease.

IntroductionClinicopathological analyses revealed that reduction in HbA1c and use of insulin independently contribute to reduction in liver fibrosis scores during the course of nonalcoholic fatty liver disease (NAFLD) development. We will test our hypothesis that lowering glucose and increasing insulin reduce liver fibrosis in NAFLD. Sodium–glucose cotransporter 2 (SGLT2) inhibitors lower insulin levels and sulfonylureas increase insulin levels, while both lower glucose levels.MethodsThis study is a 48-week, one-center (only Kanazawa University Hospital), open-label, randomized, parallel trial. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily 20 mg tofogliflozin or 0.5 mg glimepiride. The sample size was calculated to be 14 in each group with a significance level of 0.05 and power of 0.90. The design required 40 evaluable patients in this study. The primary endpoint of this study will be the improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. The secondary efficacy endpoints in the present study include organ-specific insulin sensitivity, insulin/glucagon secretion, ectopic fat accumulation, bioelectrical impedance analysis, sympathetic nerve activity, comprehensive gene expression analyses in the liver and blood cells, and gut microbiota profiling.Planned OutcomesRecruitment into this study started in November 2015 and will end in September 2020, with 40 patients randomized into the two groups. The treatment follow-up of the participants is currently ongoing and is due to finish by the end of 2022. The findings of this trial will be disseminated through peer-reviewed publications and international presentations.Trial RegistrationThis trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000020544) and ClinicalTrials.gov (NCT02649465).

Comprehensive gene expression analysis of semaphorins in oral squamous cell carcinoma

AbstractSemaphorin family members (Semaphorins; SEMAs) consist of a large family that includes both secreted and membrane‐associated proteins that are originally found to provide axon guidance in selected areas for neural development. The SEMAs have diverse biologic activities such as neuronal cellular migration, axon guidance, vasculogenesis, branching morphogenesis, and cardiac organogenesis. Recent studies have reported that SEMAs also play crucial roles in various carcinomas. However, the association and their role in oral squamous cell carcinoma (OSCC) are still poorly understood. In this study, we evaluated SEMAs mRNA expression in OSCC‐derived cell lines using quantitative reverse transcriptase‐polymerase chain reaction (qRT‐PCR) analysis and revealed the altered gene expression profile of the SEMAs in OSCC cell lines compared with human normal oral keratinocytes. We found that tendency for up‐regulation of SEMA3E, 4C, 5A, 6B, and 7A in OSCC‐derived cell lines. Especially, SEMA3E and SEMA7A mRNA were significantly up‐regulated in all OSCC‐derived cell lines. On the other hands, SEMA3A, 3C, 3F, and 6A mRNA were significantly down‐regulated in all OSCC‐derived cell lines. The expression and role of SEMAs in OSCC depend on the forms and may provide novel insights and therapeutic target for OSCCs.

Comprehensive analysis of gene expression of isolated pancreatic islets during pretransplant culture.

Background: The aim of this study was to investigate the effect of pretransplant culture on the survival of pancreatic islet grafts, and to determine the biological characteristics of isolated islets during pretransplant culture. Methods: The survival of islets from Wistar rats, transplanted to diabetic C57BL/B6 mice, was compared between fresh islets and cultured islets. A comprehensive gene expression analysis was employed to investigate biological processes during pretransplant culture, and in vitro validation studies were performed. Results: Survival of cultured xenografts was significantly prolonged as compared to that of fresh islets (fresh: 12.5 ± 1.9 days, 1-day cultured: 16.0 ± 1.3 days (p= 0.017), 3-day cultured: 17.0 ± 2.6 days (p= 0.014)). Comprehensive gene expression analysis identified significant upregulation of annotated functions associated with inflammation in cultured groups. Six proinflammatory genes, including heme oxygenase 1 (HO-1) and IL-6, were significantly upregulated during culture. Validation studies revealed significantly higher levels of IL-6 in the supernatant of cultured islets and HO-1 in the cultured islets when compared with fresh islets. Conclusion: Transplantation of cultured islets induced significant but minimal prolongation of graft survival in xenogeneic combinations. Comprehensive analysis of gene expression in cultured islets showed biological processes associated with proinflammation during culture.

Comprehensive analysis of gene expression and DNA methylation data identifies potential biomarkers and functional epigenetic modules for lung adenocarcinoma.

Lung cancer has one of the highest mortality rates of malignant neoplasms. Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer. DNA methylation is more stable than gene expression and could be used as a biomarker for early tumor diagnosis. This study is aimed to screen potential DNA methylation signatures to facilitate the diagnosis and prognosis of LUAD and integrate gene expression and DNA methylation data of LUAD to identify functional epigenetic modules. We systematically integrated gene expression and DNA methylation data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), bioinformatic models and algorithms were implemented to identify signatures and functional modules for LUAD. Three promising diagnostic and five potential prognostic signatures for LUAD were screened by rigorous filtration, and our tumor-normal classifier and prognostic model were validated in two separate data sets. Additionally, we identified functional epigenetic modules in the TCGA LUAD dataset and GEO independent validation data set. Interestingly, the MUC1 module was identified in both datasets. The potential biomarkers for the diagnosis and prognosis of LUAD are expected to be further verified in clinical practice to aid in the diagnosis and treatment of LUAD.

Biological and clinical aspects of HPV-related cancers.

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.