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PubMed1993

Cytogenetic profiling using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH).

Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) allow cytogenetic analyses of primary tumors without culture. CGH allows detection and mapping of allelic imbalance by simultaneous in situ hybridization of differentially labeled tumor (green fluorescing) and normal DNA (red fluorescing) to a normal human metaphase spread. Regions of increased or decreased copy number in the tumor are mapped onto the normal metaphase chromosomes as increases or decreases in the green to red fluorescence ratio. This technique gives a comprehensive assessment of gene dosage imbalance throughout the tumor. However, it is limited, at present, to fairly large tumors containing few normal cells. FISH, on the other hand, allows analysis of DNA sequence copy number at specific loci in single nuclei. A wide variety of DNA probes is available for FISH, including chromosome-specific probes which hybridize to alpha-satellite pericentromeric DNA regions (to detect changes in specific chromosome copy number and overall ploidy) and specific locus probes targeting 20-150 kilobase sequences (to detect specific amplifications, deletions, breakpoints, or rearrangements). FISH using these probes has been applied to interphase nuclei in touch preparations, smears from fine needle aspirates, and thin (< 6 microns) and thick (> 20 microns) sections cut from formalin-fixed, paraffin-embedded tissue. Analysis of thick sections allows accurate actual signal enumeration within the histological context. This approach may allow analysis of subtle premalignant, early malignant, and infiltrating tumors in which malignant cells must be differentiated from nonmalignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Aberrations↗

PubMed2005

Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues.

A major advantage of the mouse model lies in the increasing information on its genome, transcriptome, and proteome, as well as in the availability of a fast growing number of targeted and induced mutant alleles. However, data from comparative transcriptome and proteome analyses in this model organism are very limited. We use DNA chip-based RNA expression profiling and 2D gel electrophoresis, combined with peptide mass fingerprinting of liver and kidney, to explore the feasibility of such comprehensive gene expression analyses. Although protein analyses mostly identify known metabolic enzymes and structural proteins, transcriptome analyses reveal the differential expression of functionally diverse and not yet described genes. The comparative analysis suggests correlation between transcriptional and translational expression for the majority of genes. Significant exceptions from this correlation confirm the complementarities of both approaches. Based on RNA expression data from the 200 most differentially expressed genes, we identify chromosomal colocalization of known, as well as not yet described, gene clusters. The determination of 29 such clusters may suggest that coexpression of colocalizing genes is probably rather common.

Animals↗

PubMed2004

Protein network inference from multiple genomic data: a supervised approach.

MOTIVATION: An increasing number of observations support the hypothesis that most biological functions involve the interactions between many proteins, and that the complexity of living systems arises as a result of such interactions. In this context, the problem of inferring a global protein network for a given organism, using all available genomic data about the organism, is quickly becoming one of the main challenges in current computational biology. RESULTS: This paper presents a new method to infer protein networks from multiple types of genomic data. Based on a variant of kernel canonical correlation analysis, its originality is in the formalization of the protein network inference problem as a supervised learning problem, and in the integration of heterogeneous genomic data within this framework. We present promising results on the prediction of the protein network for the yeast Saccharomyces cerevisiae from four types of widely available data: gene expressions, protein interactions measured by yeast two-hybrid systems, protein localizations in the cell and protein phylogenetic profiles. The method is shown to outperform other unsupervised protein network inference methods. We finally conduct a comprehensive prediction of the protein network for all proteins of the yeast, which enables us to propose protein candidates for missing enzymes in a biosynthesis pathway. AVAILABILITY: Softwares are available upon request.

Artificial Intelligence↗

PubMed2025

A survey of dietary effects on tRNA abundance and modifications.

Transfer RNAs (tRNAs) play a central role in protein translation and are increasingly recognized as dynamic regulators of gene expression. Both physiological and environmental signals can modulate tRNA abundance and chemical modifications, yet the impact of dietary cues on the tRNA landscape remains poorly understood. Here, we investigated the effects of two distinct dietary interventions-low-protein and high-fat diets-on tRNA abundance and modification profiles across multiple mouse tissues. We conducted a comprehensive analysis of tRNA abundance and modification changes in response to these nutritional challenges using RNA mass spectrometry and Ordered Two-Template Relay sequencing (OTTR-seq), a modified-base-sensitive tRNA sequencing method. Our results reveal both shared and tissue-specific alterations in abundance and modifications of specific nuclear and mitochondrial genome-encoded tRNAs in response to dietary conditions at isotype, isoacceptor, and isodecoder levels. As many of the tissue-specific or diet-responsive tRNA modifications have been previously reported to affect decoding efficiency or translational fidelity, these results have implications for understanding translational adaptation in response to dietary conditions.

Journal Article↗

PubMed2026

Systematic characterization of neurotransmitter receptor dysregulation identifies a neural-related prognostic signature associated with biochemical recurrence in prostate cancer.

BACKGROUND: The nervous system is increasingly recognized to play a critical role in tumor initiation and progression. Central to this complex relationship are the interactions between neurotransmitters secreted by neurons and their receptors (neurotransmitter receptors, NTRs) expressed on cancer cells, which activate multiple intracellular signaling pathways. However, the spectrum of NTR dysregulation and its association with biochemical recurrence (BCR) in prostate cancer (PCa) has not been explored. Therefore, the aim of this study was to fill this gap. METHODS: We systematically characterized the expression profiles of 130 NTR genes by integrating bulk and single-cell transcriptomic data. Consistently dysregulated NTR (cdNTR) genes were identified and used to construct a PCa signature (PCaSig) using elastic-net regression. The robustness of PCaSig was evaluated across three independent cohorts. In addition, the associations of PCaSig with clinicopathological characteristics, genomic alterations, tumor immune-related characteristics, and biological pathways were comprehensively investigated. RESULTS: Thirteen cdNTR genes with strong cell-type specificity, particularly in luminal epithelial cells, were identified. PCaSig robustly stratified patients into distinct BCR risk groups across multiple independent cohorts and remained an independent predictor after adjustment for clinicopathological factors. High PCaSig scores were associated with aggressive clinicopathological features, elevated tumor mutation burden (TMB), suppression of neurotransmitter-related signaling, and activation of cell-cycle and immune-related pathways. Notably, PCaSig refined prognostic stratification regardless of TMB status and was associated with distinct immune-related characteristics, including immune checkpoint expression and immune cell infiltration. Incorporation of PCaSig into a clinical nomogram significantly improved prognostic accuracy and clinical net benefit. CONCLUSIONS: These findings establish NTR dysregulation as a previously underappreciated dimension of PCa and support PCaSig as a clinically relevant tool for personalized management.

Neurotransmitter receptor (NTR)↗

PubMed2026

Genome-wide identification of the Glutathione Peroxidase (GPX) gene family in Taxodium distichum and functional characterization of TdGPX9 in enhancing salt tolerance.

This study systematically identified 10 TdGPX genes in Taxodium distichum, demonstrating that the nucleocytoplasmic-localized TdGPX9 plays a pivotal role in salt stress response. Overexpression of TdGPX9 significantly enhances salt tolerance by strengthening the antioxidant defense system and improving root system plasticity under stress. Taxodium distichum is a premier coniferous species renowned for its exceptional waterlogging and salinity tolerance, serving as a vital forest resource for coastal afforestation and wetland ecological restoration. Within the physiological framework of plant stress resistance, the glutathione peroxidase (GPX) family represents a cornerstone of the antioxidant enzymatic system, playing a critical role in scavenging reactive oxygen species and maintaining cellular redox homeostasis. In this study, 10 TdGPX genes were identified via a comprehensive genome-wide analysis and mapped across eight chromosomes. These genes possess a highly conserved Thioredoxin_like domain, with structural and motif analyses revealing a well-maintained arrangement of conserved motifs within each subgroup. The promoter analysis identified a sophisticated regulatory network enriched with cis-acting elements responsive to light, phytohormones, and abiotic stresses, suggesting their integration into diverse signaling pathways. Expression profiling across various tissues and embryonic developmental stages further highlighted the versatile roles of TdGPX members in plant growth and organogenesis. Notably, qRT-PCR analysis identified the nucleocytoplasmic-localized TdGPX9 as a primary respondent to salinity. Functional validation demonstrated that TdGPX9 overexpression significantly enhances salt tolerance in transgenic Arabidopsis and T. distichum callus by strengthening the antioxidant defense system. Furthermore, TdGPX9 promoted root system plasticity under stress, as evidenced by increased lateral root density. These findings provide a systematic basis for understanding the redox-regulatory mechanisms in baldcypress and offer vital genetic resources for improving forest resilience in coastal wetland ecosystems.

Salt Tolerance↗

PubMed2005

Gene expression profiling of human atrial myocardium with atrial fibrillation by DNA microarray analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered arrhythmia in the clinical setting. However, a comprehensive investigation of the molecular mechanism of AF has not been performed. The aim of this study was to clarify transcriptional profiling of genes modulated in the atrium of AF patients using DNA microarray technology. METHODS: We obtained 17 fresh cardiac specimens, right atrial appendages, isolated from 10 patients with normal sinus rhythm and seven chronic AF patients who underwent cardiac surgery. Affymetrix GeneChip (Human Genome U95A) investigating 12,000 human genes was used for each specimen. Quantitative analysis of selected genes was performed by the real-time PCR method. RESULTS: The left atrial diameter in the AF group was greater than that in the sinus rhythm group. We could identify 33 AF-specific genes that were significantly activated (>1.5-fold), compared with the sinus rhythm group, including an ion channel, an antioxidant, an inflammation, three cell growth/cell cycle, three transcription such as nuclear factor-interleukin 6-beta, several cell signaling and several protein genes, and seven expressed sequence tags (ESTs). In contrast, we found 63 sinus rhythm-specific genes, including several cell signaling/communication such as sarcoplasmic reticulum Ca2+-ATPase 2, several cellular respiration and energy production and two antiproliferative or negative regulator of cell growth genes, and 22 ESTs. CONCLUSIONS: The present study demonstrated that about one hundred genes were modulated in the atria of AF patients. These findings suggest that these genes may play critical roles in the initiation or perpetuation of AF and the pathophysiology of atrial remodeling.

Adolescent↗

PubMed2026

Single-cell transcriptomics on FFPE placenta: A novel method for comprehensive exploration of an entire placental section.

INTRODUCTION: The placenta's complex cellular diversity challenges traditional transcriptomic analyses. Single-cell RNA sequencing (scRNA-seq) offers breakthrough capabilities by enabling transcriptome profiling at the single-cell level. However, traditional scRNA-seq relies on fresh or frozen samples, which present practical storage and quality challenges. Applying scRNA-seq to Formalin-Fixed, Paraffin-Embedded (FFPE) placentas could harness archived samples for clinical insights. METHODS: We used 10x Genomics Flex technology to analyze 8 non-pathological placentas ranging from 21 + 6 weeks of gestation (WoG) to 39 + 4 WoG. RESULTS: Our approach identifies diverse cell populations and allows us to discern maternal from fetal cells. Despite sample size limitations, the method yields comparable data to prior fresh/frozen tissue studies and we complete these data by integrating new molecular markers. The potential to correlate single-cell results with histopathology enables us to conduct an in-depth analysis across entire placental sections by concurrently addressing both fetal and maternal cells. We could thus confirm molecular markers like KRT5/6 using immunohistochemistry by revisiting the slide. DISCUSSION: This innovation could aid in understanding focal anomalies observed on standard histology slides, thereby enhancing traditional histopathological assessments. Given its practicality, integrating our method into routine practice is both feasible and promising.

Differentially expressed genes (DEG)↗

PubMed2006

Genome-wide screening of dioxin-responsive genes in fetal brain: bioinformatic and experimental approaches.

Many of the effects of dioxins, which are potent environmental pollutants and teratogens, are mediated through the aryl hydrocarbon receptor, also known as the dioxin receptor. The purpose of the present study was to characterize dioxin-responsive genes in a comprehensive manner using two complementary approaches: bioinformatic analysis and microarray analysis. First, we characterized the overall distribution of the cis-regulatory element for the dioxin-responsive element sequence (DRE) 'gcgtg' within putative promoter regions. We assembled the upstream sequences 10 kb from the transcription start site and evaluated their location and frequency in the human and mouse genomes. Second, we characterized the expression profile of mouse embryonic day 12 fetal brain exposed to 2,3,7,8-tetrarchlorodibenzo-p-dioxin. The distributions of 26,680 DREs among 2,843 human genes and 98,711 DREs among 18,541 mouse genes were examined. In both species, the DREs tended to be located close to the transcription start site. Forty genes exhibited significant induction or repression following dioxin exposure in fetal mice. The set of genes exhibited a strong functional coherence, with statistically significant enrichment in organogenesis and the DNA-dependent regulation of transcription, according to Gene Ontology annotations. In both humans and mice, DREs were preferentially distributed close to transcription start sites. Evolutionary conservation of this unique DRE distribution pattern suggests that DREs may be involved in transcriptional regulation. In mice, prenatal dioxin exposure altered the expression of 10 transcription factors, many of which have been documented to play a role in organogenesis. These genes may represent potential mediators of dioxin's effects in fetal tissues.

Animals↗

PubMed2005

Systems biology in drug safety and metabolism: integration of microarray, real-time PCR and enzyme approaches.

The last decade has seen a rapid expansion in the field of functional genomics, due mainly to the global gene expression profiling capabilities provided by techniques, such as microarray analysis. Application of these technologies in fields as diverse as plant research, to public health and environmental sciences, forensic science and drug research, shows the versatility of these tools and the promise they hold for revolutionizing research in the life sciences. In drug discovery, attempts have been made to use functional genomics in target identification and validation, lead selection and optimization, and in preclinical studies to predict clinical outcome. These studies have provided a plethora of data and undoubtedly expanded our understanding of genetic alterations in diseased and non-diseased states, but the benefits that these technologies hold have not yet been fully realized. This review discusses how a comprehensive approach to gene regulation studies, a 'systems biology' approach, is being applied in a drug development setting to address mechanism-based questions and issues raised by regulatory authorities.

Cytochrome P-450 Enzyme System↗

PubMed2026

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-κB, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

PubMed2006

Transcriptional profiling of brain-derived-neurotrophic factor-induced neuronal plasticity: a novel role for nociceptin in hippocampal neurite outgrowth.

Brain derived neurotrophic factor (BDNF) exhibits a sequence of actions on neurons ranging from acute enhancement of transmission to long-term promotion of neurite outgrowth and synaptogenesis associated with learning and memory. The manifold effects of BDNF on neuronal modifications may be mediated by genomic alterations. We previously found that BDNF treatment acutely increases transcription of the synaptic vesicle protein Rab3A, required for trophin-induced synaptic plasticity, as well as the peptide VGF, which increases during learning. To elucidate comprehensive transcriptional programs associated with short- and long-term BDNF exposure, we now examine mRNA abundance and complexity using Affymetrix GeneChips in cultured hippocampal neurons. Consistent with the modulation of synaptic plasticity, BDNF treatment (3-6 h) induced mRNAs encoding the synapse-associated proteins synaptojanin 2, neuronal pentraxin 1, septin 9, and ryanodine receptor 2. BDNF also induced expression of mRNAs encoding neuropeptides (6-12 h), including prepronociceptin, neuropeptide Y, and secretogranin. To determine whether these neuropeptides induced by BDNF mediate neuronal development, we examined their effects on hippocampal neurons. The four mature peptides derived from post-translational processing of the ppNociceptin propeptide induced the expression of several immediate early genes in hippocampal cultures, indicating neuronal activation. To examine the significance of activation, the effects of nociceptin (orphanin FQ) and nocistatin on neurite outgrowth were examined. Quantitative morphometric analysis revealed that nociceptin significantly increased both average neurite length and average number of neurites per neuron, while nocistatin had no effect on these parameters. These results reveal a novel role for nociceptin and suggest that these neuropeptide systems may contribute to the regulation of neuronal function by BDNF.

Animals↗

PubMed2006

Optimized PCR fragments for heteroduplex analysis of the whole human mitochondrial genome with denaturing HPLC.

Denaturing high pressure liquid chromatography (dHPLC) is an efficient method for discovery of unknown mutations by heteroduplex analysis of PCR fragments. For comprehensive mutation scanning of the whole 16.569 bp human mitochondrial genome, we developed a set of 67 primer pairs defining overlapping PCR fragments that are well suited for heteroduplex analysis. The aim of our optimization efforts was to ensure that point mutations are detectable at every nucleotide position of each amplicon. Some GC-rich regions of mitochondrial DNA (mtDNA) were found to have unfavourable melting profiles in all possible amplicons, therefore requiring GC-clamps at the end of one or both oligonucleotide PCR primers. Following detection of a heteroduplex pattern by dHPLC, our primers can also be employed for DNA sequencing to identify the underlying mutation. In case of heteroplasmic mutations with a low proportion of mutant mtDNA, a fragment collector is useful to recover the heteroduplex peak, which contains mutant and wildtype DNA molecules in a 1:1 ratio.

Base Sequence↗

PubMed2004

Profiling and comprehensive expression analysis of ABC transporter solute-binding proteins of Bacillus subtilis membrane based on a proteomic approach.

We analyzed ABC transporter solute-binding proteins (SBPs) of the Bacillus subtilis membrane using a proteomic approach. We prepared a washed cell membrane fraction that was insoluble in 134 mM nondetergent sulfobetaine and then extracted proteins using mixtures of detergents in a stepwise manner. The membrane proteins were resolved by three two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) or two one-dimensional (1-D) PAGE procedures, electroblotted, and digested in the presence of 5% or 80% acetonitrile. Thereafter, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF MS) identified 637 proteins corresponding to 15.9% of the total cellular proteins. We predicted that among these, 256 were membrane proteins, 101 were lipoproteins or secretory proteins and 280 were soluble proteins containing peripheral proteins that function in both the cytoplasm and the cell membrane such as SecA and FtsY. Among the 637 proteins, we identified 30 SBPs among 38 importers predicted by a bioinformatic search of the genome. We confirmed expression of the genes for the 30 SBPs using DNA microarray analysis. We compared the 2-D gel separation profiles of submembrane fractions solubilized by 1% n-dodecyl-beta-D-maltoside from cells cultured on Luria Bertani (LB), S7, and S7 medium without glutamate as well as DNA microarray data on LB and S7. The results suggested that YcdH, YtmK and YurO are binding proteins for Mn(++), glutamate and glucose, respectively, and that YqiX and YxeM are binding proteins for amino acids (tryptophan in S7 medium).

ATP-Binding Cassette Transporters↗

PubMed2006

The transcriptional regulatory network of the amino acid producer Corynebacterium glutamicum.

The complete nucleotide sequence of the Corynebacterium glutamicum ATCC 13032 genome was previously determined and allowed the reliable prediction of 3002 protein-coding genes within this genome. Using computational methods, we have defined 158 genes, which form the minimal repertoire for proteins that presumably act as transcriptional regulators of gene expression. Most of these regulatory proteins have a direct role as DNA-binding transcriptional regulator, while others either have less well-defined functions in transcriptional regulation or even more general functions, such as the sigma factors. Recent advances in genome-wide transcriptional profiling of C. glutamicum generated a huge amount of data on regulation of gene expression. To understand transcriptional regulation of gene expression from the perspective of systems biology, rather than from the analysis of an individual regulatory protein, we compiled the current knowledge on the defined DNA-binding transcriptional regulators and their physiological role in modulating transcription in response to environmental signals. This comprehensive data collection provides a solid basis for database-guided reconstructions of the gene regulatory network of C. glutamicum, currently comprising 56 transcriptional regulators that exert 411 regulatory interactions to control gene expression. A graphical reconstruction revealed first insights into the functional modularity, the hierarchical architecture and the topological design principles of the transcriptional regulatory network of C. glutamicum.

Amino Acids↗

PubMed2026

From standardization to precision medicine: Evolution of European Leukemianet recommendations in Philadelphia-negative myeloproliferative neoplasms.

The European LeukemiaNet (ELN) recommendations have been instrumental in shaping the diagnosis, risk stratification, and management of Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Over the past two decades, these recommendations have evolved from consensus-based frameworks focused on response standardization to increasingly sophisticated, evidence-based and biologically informed approaches. Early efforts primarily aimed to harmonize response criteria across clinical studies, establishing a foundation for consistent therapeutic evaluation. Subsequent updates introduced risk-adapted treatment strategies centered on thrombotic risk, reflecting the major determinants of morbidity and mortality in these disorders. However, the limitations of surrogate endpoints prompted a shift toward clinically meaningful outcomes, including symptom burden, vascular events, and disease progression. More recent advances have been driven by the integration of molecular genetics and the adoption of structured evidence-based methodologies, enabling refined diagnostic classification and more accurate prognostic assessment. Contemporary ELN frameworks increasingly incorporate dynamic clinical parameters, genomic profiling, and emerging biomarkers, supporting a transition toward individualized, risk-adapted therapeutic strategies. Beyond their role in standardizing MPN management, ELN recommendations have also influenced clinical trial design, endpoint selection, risk stratification, and therapeutic decision-making. Evidence from prospective studies and real-world cohorts supports the clinical applicability of these frameworks, although their implementation remains heterogeneous across healthcare settings. This review provides a comprehensive and critical overview of the evolution and implementation of ELN recommendations, highlighting their impact on clinical research and routine practice, current limitations, and future directions toward precision medicine in Philadelphia-negative MPNs.

Essential thrombocythemia↗

PubMed2003

Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies.

When using gene expression profiling to understand human tumors, one is often confronted with long lists of genes that need to be further categorized into meaningful data. We performed a comprehensive evaluation and comparison of gene expression profiles obtained from pancreatic cancers to determine those genes most differentially expressed and thus with the most promise for translation into clinically useful targets. cDNA was prepared from 50 samples of normal pancreas or duodenal mucosal tissues, 7 samples of chronic pancreatitis, and 39 samples of pancreas cancer tissues or cancer cell lines and hybridized to the complete Affymetrix Human Genome U133 GeneChip set (arrays U133A and U133B) for simultaneous analysis of 45,000 fragments corresponding to 33,000 known genes and 6,000 expressed sequence tags. Genes expressed at levels at least 3-fold greater in the pancreatic cancers as compared with nonneoplastic tissues were identified. Three hundred seventy-seven Affymetrix fragments were identified as having > or = 3-fold expression levels in pancreas cancer specimens as compared with nonneoplastic tissues, corresponding to 234 known genes. Serial analysis of gene expression libraries (http://www.ncbi.nlm.nih.gov/SAGE/) of two normal pancreatic ductal cell cultures (HX and H126) were used to exclude 17 genes with high expression levels in the normal duct epithelium (more than five tags/library). Of the remaining 217 known genes, 75 have been previously reported as highly expressed in pancreatic cancers, while the remaining 142 genes are novel. We used principal components analysis (PCA) to identify the genes among these 217 identified as the most differentially expressed and specific to pancreatic cancer tissues or cell lines. Among the most differentially expressed genes identified by PCA were Mesothelin, Muc4, Muc5A/C, Kallikrein 10, Transglutaminase 2, Fascin, TMPRSS3 and stratifin. The differential expression identified by PCA for these genes indicates they are among the more attractive targets for novel therapeutic targets, tumor markers, or as a means of screening pancreatic cancer samples for information regarding tumor classification or potential therapeutic responses. Our findings were also compared in detail to the previously reported findings of highly expressed genes in other studies of global gene expression in pancreatic cancers. We found that robust changes in gene expression were most often identified by more than one gene expression platform. Forty genes were identified by more than one method (U133 oligonucleotide arrays, cDNA arrays or serial analysis of gene expression), and 6 of these genes were identified by all three methods. Our findings identify a novel set of genes as highly expressed in pancreatic cancer, validate the differential expression of previously reported genes, and provide additional support for those genes most differentially expressed to be translated into clinically useful targets.

Carcinoma, Pancreatic Ductal↗

PubMed2026

Genome-wide identification and characterization of 1-amino-cyclopropane-1- carboxylate synthase (ACS) gene family in Carica papaya and expression insights in response to hormone stress.

ACC-synthase (1-aminocyclopropane-1-carboxylate synthase), also known as the ACS gene, plays a pivotal role in ethylene production, which is of great importance in the fruit ripening process for producing saleable yield (marketable fruit). The ACS gene family presumably controls stress responses, plant growth and development, and particularly fruit ripening. Computational biology was used as an essential tool to identify seven ACS genes in Carica papaya (red hermaphrodite) using an RNA-seq database (NCBI GEO). Further, the phylogenetic relationships of ACS genes determined gene family resemblance in the genomes of Hordeum vulgare, Musa acuminata, C. papaya, and Arabidopsis thaliana; therefore, the identified gene families were further classified into four distinct clades (Type-I, Type-II, Type-III, and Type-IV) in alignment with the well-established Arabidopsis classification. Moreover, encompassing gene structure, domain motifs, cis-element phylogenetic profiling, synteny, and transcriptomic profiling unveiled latent structural and functional attributes within CpACS genes. Through segmental duplication of CpACS, insights into evolutionary duplication events were predicted. The paralogous behavior of ACS genes in C. papaya and a comprehensive transcriptomic analysis demonstrated both up- and down-regulation patterns in response to ethylene treatment at different time points during the fruit ripening process, using the papaya manual handbook V2 (2021). Gene expression showed upregulation of two essential CpACS genes, CpACS5 and CpACS6. RT-qPCR validates the expression of these important genes during fruit ripening. However, one gene, CpACS7, is expressed in the later stages of fruit development. Our results demonstrated novel avenues for understanding the expression pathways of the ACS gene family in red hermaphrodite papaya, and most of these genes were linked to regulating various abiotic stresses, plant growth, and fruit development.

Carica↗