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PubMed2000

Tibetan and Andean patterns of adaptation to high-altitude hypoxia.

Understanding the workings of the evolutionary process in contemporary humans requires linking the evolutionary history of traits with their current genetics and biology. Unusual environments provide natural experimental settings to investigate evolution and adaptation. The example of high-altitude hypoxia illustrates some of the progress and many of the remaining challenges for studies of evolution in contemporary populations. Current studies exemplify the frequently encountered problem of determining whether large, consistent population differences in mean values of a trait reflect genetic differences. In this review I describe 4 quantitative traits that provide evidence that indigenous populations of the Tibetan and Andean plateaus differ in their phenotypic adaptive responses to high-altitude hypoxia. These 4 traits are resting ventilation, hypoxic ventilatory response, oxygen saturation, and hemoglobin concentration. The Tibetan means of the first 2 traits were more than 0.5 standard deviation higher than the Aymara means, whereas the Tibetan means were more than 1 standard deviation lower than the Aymara means for the last 2 traits. Quantitative genetic analyses of within-population variance revealed significant genetic variance in all 4 traits in the Tibetan population but only in hypoxic ventilatory response and hemoglobin concentration in the Aymara population. A major gene for oxygen saturation was detected among the Tibetans. These findings are interpreted as indirect evidence of population genetic differences. It appears that the biological characteristics of sea-level humans did not constrain high-altitude colonists of the 2 plateaus to a single adaptive response. Instead, microevolutionary processes may have operated differently in the geographically separated Tibetan and Andean populations exposed to the same environmental stress. Knowledge of the genetic bases of these traits will be necessary to evaluate these inferences. Future research will likely be directed toward determining whether the population means reflect differences identified at the chromosomal level. Future research will also likely consider the biological pathways and environmental influences linking genotypes to phenotypes, the costs and benefits of the Tibetan and Andean patterns of adaptation, and the question of whether the observed phenotypes are indeed adaptations that enhance Darwinian fitness.

Adaptation, Physiological↗

PubMed2001

PIES, a protein interaction extraction system.

We consider the problem of extracting, manipulating, and managing biological pathways, especially protein-protein interaction pathways. We discuss here the Protein Interaction Extraction System (PIES). PIES is contructed on top of three main technologies: Kleisli, BioNLP, and Graphviz. Kleisli is a broad-scale data integration system that we use for downloading Medline abstracts and for general manipulation and management of pathway/interaction databases. BioNLP is a natural language-based information extraction module that we use for analysing Medline abstracts and to extract precise protein-protein and other interaction information. Graphviz is a graphical layout package developed for directed graphs that we use for visualization of the extracted pathways. PIES can be augmented with various means for extracting protein interaction information from sequence databases, for example, by using Kleisli's power to integrate sequence comparison tools to detect gene fusion events in sequence databases.

Abstracting and Indexing↗

PubMedDate not supplied

CellML: its future, present and past.

Advances in biotechnology and experimental techniques have lead to the elucidation of vast amounts of biological data. Mathematical models provide a method of analysing this data; however, there are two issues that need to be addressed: (1) the need for standards for defining cell models so they can, for example, be exchanged across the World Wide Web, and also read into simulation software in a consistent format and (2) eliminating the errors which arise with the current method of model publication. CellML has evolved to meet these needs of the modelling community. CellML is a free, open-source, eXtensible markup language based standard for defining mathematical models of cellular function. In this paper we summarise the structure of CellML, its current applications (including biological pathway and electrophysiological models), and its future development--in particular, the development of toolsets and the integration of ontologies.

Algorithms↗

PubMed2003

New therapeutic strategies for soft tissue sarcomas.

The treatment of patients with metastatic soft tissue sarcomas (STS) is complex. There are limited agents available and many are associated with significant toxicity. When evaluating a patient with metastatic disease, physicians should ask themselves whether there is a role for surgery to render the patient free of disease. Combination chemotherapy in patients who have not received chemotherapy in the adjuvant setting is one option, particularly in a young patient with a good performance status. Sequential single-agent therapy for patients who are more elderly or debilitated by their disease may be more appropriate. Gemcitabine appears to be an agent with activity, particularly in patients with leiomyosarcomas. The data regarding prolonged gemcitabine infusions suggest improved activity that was predicted based on prolonged intracellular gemcitabine levels. Because of these data, the prolonged infusion schedule should be used. In addition, because of the paucity of effective agents, consideration of clinical trial participation for patients with newly diagnosed metastatic disease is appropriate, particularly in chemotherapy-insensitive histologies. The role of the newer agents (eg, ecteinascidin-743, epothilones, and mammalian target of rapamycin) is undefined. Ecteinascidin-743 has been the most extensively tested agent, and its ability to slow growth kinetics of a tumor and stabilize it clinically is intriguing. Data regarding the response to BMS-247550 will be published shortly and will help define the further role of epothilones in this disease. There is a preclinical rationale that makes the mammalian target of rapamycin inhibitors attractive for the treatment of muscle-derived neoplasms. In addition, there are cell-line data suggesting activity in rhabdomyosarcoma. These agents are being tested in adult STS and will likely be tested in pediatric histologies when there are more safety data available in that population. SU11248 will continue to be tested in patients refractory to imatinib mesylate and may well prove to be another active agent for patients with gastrointestinal stromal tumors. As depicted by the analysis of gemcitabine efficacy, agents with activity in a subgroup of STS may be overlooked by the "come one come all" approach to clinical trials in STS. Identifying key targets in specific STS will be helpful in the testing of newer molecularly targeted agents. Biologic differences will support histology-specific trials to better understand the activity of an agent in a specific disease site or specifically target a biologic pathway with relevance to the malignant potential of the disease. For future clinical trials in STS to achieve the goal of histology-specific trials, cooperative group and multi-institutional trials will be required to obtain the appropriate patients with these rare histologies. It will also be increasingly important to be committed to obtaining tumor tissue in these patients to validate hypotheses regarding tumor biology and the effectiveness of therapeutic agents.

Antineoplastic Agents↗

PubMed2002

Proteomics and its trends facing nature's complexity.

The complexity of nature is tremendous, particularly at the epigenetic level. Proteomic studies must therefore complement genomic discoveries to better understand biological processes. Because of the very large number of modified proteins and their great variability in physico-chemical properties, no single method can be used to analyze all of them. Mass spectrometry has demonstrated its superior ability to rapidly identify and partially characterize numerous proteins in low abundance and has become a central element in most proteomic projects. Studies of protein function are necessary to understand biological pathways and this is being tackled using several approaches such as two hybrid systems, phage technology or affinity methods. Finally, mathematical and bioinformatic developments will be essential to study nature's complex systems.

Computational Biology↗

PubMed2003

New perspectives on growth factor-sex steroid interaction in the prostate.

Many organs respond to both sex steroids and growth factors. Regulation of these pathways is integral to cell-cell communications during development and aberrant changes cause disease pathogenesis. Traditionally, paracrine and endocrine actions of growth factors and steroid hormones are considered independently. Recently, new data indicated that activin/TGFbeta and sex steroid signalling are linked; explicitly, that the pathways cross-talk intracellularly. Here we present new perspectives on these interactions, using examples predominantly from the prostate, as it is a well-characterised organ in this context. While this information provides insight to the potential mechanisms behind these interactions, it also presents a new challenge; the action of any of these factors cannot be considered exclusively without considering the impact on the other biological pathways.

Activins↗

PubMed2006

Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing.

Advances in molecular biology and neuroimaging have provided a unique opportunity to explore the relationships between genes, brain, and behavior. In this review, we will briefly outline the rationale for studying genetic effects on brain function with neuroimaging. We will then use studies of genetically driven variation in serotonin transporter function on corticolimbic structure and function to highlight the effectiveness of this strategy to delineate biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. In a series of studies, a relatively frequent regulatory variant of the human serotonin transporter gene (5-HTTLPR) has been demonstrated to bias the reactivity of the amygdala to salient environmental cues. Moreover, the 5-HTTLPR affects the development of a broader corticolimbic circuit and alters the functional integration of emotional information between the amygdala and medial prefrontal cortex. In turn, corticolimbic circuit function predicts individual differences in an experimental index of temperamental anxiety and, thus, might reflect a predictive biological marker of increased risk for mood disorders associated with the 5-HTTLPR.

Alleles↗

PubMed2004

Genome-based proteomics.

Protein-protein interactions play crucial roles in various biological pathways and functions. Therefore, the characterization of protein levels and also the network of interactions within an organism would contribute considerably to the understanding of life. The availability of the human genome sequence has created a range of new possibilities for biomedical research. A crucial challenge is to utilize the genetic information for better understanding of protein distribution and function in normal as well as in pathological biological processes. In this review, we have focused on different platforms used for systematic genome-based proteome analyses. These technologies are in many ways complementary and should be seen as various ways to elucidate different functions of the proteome.

Chromatography, Liquid↗

PubMed2006

Serpins, the vasculature, and viral therapeutics.

Serine protease inhibitors, termed serpins, are key regulators of numerous biological pathways that initiate inflammation, coagulation, angiogenesis, apoptosis, extra-cellular matrix composition and complement activation responses. Viruses have encoded serpins to guard themselves from host immune attack. The myxoma virus which infects rabbits secretes a highly potent anti-inflammatory serpin, Serp-1, which targets thrombolytic and thrombotic proteases as a means to fend off coagulation and inflammatory reactions to viral infection. These reactions act as a defense, produced by the host, to counter viral infection and invasion. When infused in animals after vascular injury, Serp-1 elicits exceptional anti-inflammatory activity, whereas the mammalian serpin, plasminogen activator inhibitor-1 (PAI-1), which also targets thrombotic and thrombolytic proteases can induce a pro-thrombotic response. During arterial injury, PAI-1 is highly expressed and increased PAI-1 concentration can result in acute thrombosis after aortic transplant in mouse models. The reactive center loop amino acid sequence is a fingerprint for serpin function and this function is highly sequence specific such that modification in this sequence can markedly alter activity. For instance, the alteration of the serpin reactive site loop P1-P1I amino acid sequence nullified the anti-inflammatory activity of Serp-1 and modification of P2-P7 initiated a pro-inflammatory response with vascular remodeling with aneurysm formation. Furthermore Serp-1 has demonstrated the capacity to utilize a mammalian serine protease receptor, the urokinase-type plasminogen activator receptor (uPAR), to alter cellular signaling in part through the actin binding protein cytoskeletal system (via filamin B). In this review, the molecular mechanisms relating inflammation and coagulation pathways to atherosclerosis and how the viral serpin, Serp-1, modifies these pathways in order to exhibit this profound anti-inflammatory activity without associated adverse thrombosis are discussed. Viral and vascular serpins targeting the thrombolytic cascade represent a potential new and untapped therapeutic resource.

Animals↗

PubMed2002

Deciphering peripheral nerve myelination by using Schwann cell expression profiling.

Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.

Animals↗

PubMed1994

Does wild-type p53 play a role in normal cell differentiation?

Inactivation of the p53 tumor suppressor gene plays a major role in malignant transformation. The central question in this issue is concerned with the understanding of the function of p53 in normal cells and its deregulation in cancer cells. Several in vitro and in vivo experimental models have indicated that induction of cells to undergo differentiation involve up-regulation in the expression of the p53. In the case of B cell differentiation, p53 was found to be involved in several steps of the differentiation pathway. The conclusion that p53 plays a role in normal development and differentiation in vivo is substantiated by the observation that p53 is expressed during embryonic development and is detected at low levels in a number of organs of adult mice. Accentuated levels of p53 in testes of adult mice, suggests that p53 plays a role in the meiotic process of spermatogenesis. B cell differentiation and spermatogenesis are biological pathways which normally involve DNA reshuffling and rearrangements. In accordance with the notion that p53 is associated with DNA repair it is tempting to speculate that at least in these physiological pathways p53 functions as a master gene that controls genome integrity.

Animals↗

PubMed2004

ISG15: the immunological kin of ubiquitin.

Since the discovery of ubiquitin in 1975, the poly-ubiquitylation pathway has earned a prominent place in biomedical research as the "garbage disposal" system of the cell. Modification with poly-ubiquitin chains plays an important role in normal protein turnover and also in removing damaged or misfolded proteins. More recently, the elucidation of mono-ubiquitylation of protein substrates has shown additional important roles for ubiquitylation in processes, such as transcriptional regulation, viral budding, and receptor internalization. Intriguingly, this voyage of discovery is now repeating itself with a new generation of ubiquitin-like (ubl) modifiers, such as SUMO and NEDD8. The functional consequences of SUMO and NEDD8 modification are thus beginning to be revealed. A less known member of this ubiquitin-like family is ISG 15, a modifier encoded by an interferon-stimulated gene. Recent publications have ascribed important functions for this molecule in various biological pathways from pregnancy to innate immune responses. Furthermore, ISG 15 has been found to modify several important molecules and affect type I interferon signal transduction. Here, we review ISG 15-related work and highlight important biological questions which need to be posed in order to further elucidate the biological consequences of ISG15 and ISG15 modification.

Amino Acid Sequence↗

PubMed1997

Switching of gene expression: analysis of the factors that spatially and temporally regulate plant gene expression.

In this chapter, we have reviewed the present research and understanding of several families of transcription factors in plants. From this information, it appears there is good conservation between the types of transcription factors in plants and animals. However, there are several types of factors which have been isolated in plants that remain to be documented in animals (e.g., HD-Zip and GT). These as well as the presence of two types of TATA-binding proteins (TBPs) in plants suggest that although transcription in eukaryotes is highly conserved, fundamental differences may exist. Despite the differences, the modes of regulating transcription are well conserved. Figure 3 summarizes these modes of regulation. In recent years, the role of chromatin structure as well as subcellular localization have been the focus of a vast amount of research in mammals, Drosophila and yeast. However, very little research in these areas has been done in plants. Isolation of genes such as Curly leaf suggest a conservation of genes that influence the formation of heterochromatin-like structures. Whether or not this gene influences chromatin/heterochromatin structure in plants, however, remains to be tested. The study of nuclear localization of factors such as COP1 and KN1 is now leading to models for regulating nuclear transport as well as intercellular transport of transcription factors. Further study of the inter- and intracellular movement of these and other transcription factors may provide information on new modes of regulating transcription. In addition to understanding the role chromatin structure and subcellular localization of transcription factors may have on transcription initiation, the biological role of many plant transcription factors remains to be identified. Several approaches may be taken to understand the mechanisms by which transcription factors influence biochemical and physiological processes in the plant. These steps include 1) identification of the DNA-binding sites of the factors as well as the promoter regions which contain these sites. Presently, this approach is limiting in that not many non-coding regions have been sequenced and characterized in detail. Furthermore, the presence of a putative binding site within a promoter does not necessarily indicate that the factor will bind to the site in vivo. 2) Analysis of the binding affinity for a particular factor to a binding site in comparison to other related factors, via in vitro competition assays and quantitative titrations. This will provide information on how strongly these factors are binding to the sites, but without knowledge of all the factors present in a single cell it is difficult to recreate the in vivo conditions. 3) Generation of transgenic plants or microinjection of DNA/RNA to express a particular factor ectopically, reduce expression of the factor via antisense expression, and creation of dominant negative mutants by overexpression of key dimerization domains may provide information concerning what biological pathways these factors influence. 4) Isolation of mutations in particular transcription factors has been extremely informative in floral development. However, this approach usually entails isolation of a mutant due to a phenotype and eventual mutated locus. The cloning of the locus may or may not involve a transcription factor. 5) Many plant transcription factors have been isolated via sequence similarity to other previously identified and/or characterized transcription factors. However, the biological role of may of these factors is not known. In addition to ectopic expression of these factors by creating transgenic plants, isolation of a loss-of-function mutation may provide valuable information concerning the role of this factor in vivo. Many loss-of-function mutations in MADS box genes have led to a better understanding of how the MADS domain proteins interact with one another as well as how they influence floral development. (ABSTRACT TRUNCATED)

Cell Compartmentation↗

PubMed2025

Longitudinal Multi-Organ Transcriptomic Atlas of Salt-Induced Hypertension.

BACKGROUND: Salt-sensitive hypertension is a prevalent and clinically significant subtype of hypertension, where increased dietary salt intake elevates blood pressure and causes injury to multiple organ systems. Despite extensive research, dynamic molecular changes and conserved versus organ-specific transcriptional programs in hypertensive multi-organ damage remain poorly understood. Defining complex molecular pathways both in a temporal sequence and in an organ-specific manner is essential for developing targeted, precision therapies to mitigate hypertensive disease burden. METHODS: We generated a longitudinal multi-organ transcriptomic atlas of salt-sensitive hypertension using RNA sequencing of kidney cortex, kidney medulla, heart, and liver from Dahl salt-sensitive rats across four disease stages. A comprehensive bioinformatic analysis mapped dynamic transcriptional programs, evaluated 50 biological pathways, and defined upstream regulators. Histological and biochemical assays complemented transcriptomic analysis, while integration with human genome-wide association studies (GWAS) and compound-transcriptome analysis provided translational insights and identified candidate therapeutics. RESULTS: Salt-induced hypertension elicited both shared and tissue-specific transcriptional programs that evolved with disease progression. The kidney medulla showed robust early immune activation with metabolic suppression, while the cortex exhibited transient metabolic activation before declining and initiating immune activation. The liver and heart showed time-dependent metabolic and inflammatory remodeling. Cross-organ comparisons revealed a shared early proliferative response that converged on proinflammatory and fibrotic signatures. Upstream regulator analysis identified 79 time- and tissue-specific transcription factors associated with gene expression dynamics. GWAS integration analysis revealed endocrine signaling, ion transport, lipid metabolism, and detoxification as conserved pathways across species, underscoring the translational relevance of the model and study. Predictive compound-transcriptome analyses identified kinase inhibitors targeting phosphoinositide 3-kinase, mechanistic target of rapamycin and cyclin-dependent kinases as top candidates to counteract maladaptive transcriptional programs. CONCLUSIONS: This study defines temporal and tissue-specific transcriptomic remodeling in salt-sensitive hypertension and highlights the need for precision interventions to prevent progressive organ damage.

Journal Article↗

PubMed2001

Transcriptional regulation and function during the human cell cycle.

We report here the transcriptional profiling of the cell cycle on a genome-wide scale in human fibroblasts. We identified approximately 700 genes that display transcriptional fluctuation with a periodicity consistent with that of the cell cycle. Systematic analysis of these genes revealed functional organization within groups of coregulated transcripts. A diverse set of cytoskeletal reorganization genes exhibit cell-cycle-dependent regulation, indicating that biological pathways are redirected for the execution of cell division. Many genes involved in cell motility and remodeling of the extracellular matrix are expressed predominantly in M phase, indicating a mechanism for balancing proliferative and invasive cellular behavior. Transcripts upregulated during S phase displayed extensive overlap with genes induced by DNA damage; cell-cycle-regulated transcripts may therefore constitute coherent programs used in response to external stimuli. Our data also provide clues to biological function for hundreds of previously uncharacterized human genes.

Apoptosis↗

PubMed2026

Multilevel genomic, transcriptomic, and epidemiologic evidence linking diabetic retinopathy to Alzheimer disease.

BACKGROUND: Diabetic retinopathy (DR) and Alzheimer disease (AD) share metabolic and vascular dysfunctions, but the extent to which they reflect overlapping genetic susceptibility and neurovascular-metabolic regulatory pathways remains unclear. We combined multi-omics analyses with population-based data to examine the genetic convergence, cellular pathways, and longitudinal association between DR and AD. METHODS: We performed a two-sample Mendelian randomisation (MR) to estimate the association between genetically predicted DR liability and AD risk. We used Bayesian colocalisation analysis to identify shared genomic loci, and summary-data-based MR (SMR) to detect expression-mediated genes jointly associated with DR and AD. We analysed single-cell RNA sequencing data to characterise shared cellular features and related biological pathways. We also conducted an MR-based mediation analysis to explore whether lipid-related, metabolic, or inflammatory traits mediated the observed DR-AD association, and a longitudinal analysis of the UK Biobank cohort to assess the association between DR and incident AD. RESULTS: With the MR analysis, we found that genetically predicted liability to DR was associated with a modest increase in AD risk. Colocalisation analysis supported a shared genetic signal. We identified three genes with shared expression-mediated associations across DR and AD through SMR. Functional enrichment analyses revealed partially overlapping neurovascular and metabolic pathways. Using MR-based mediation analysis, we found no significant intermediary traits linking DR and AD. Findings from the UK Biobank cohort were directionally consistent with the genetic analyses. CONCLUSIONS: Genetic liability to DR is associated with an increased risk of AD and is accompanied by shared expression-mediated effects and convergent neurovascular-metabolic pathways. These findings support the possibility that DR may serve as a clinically accessible indicator of increased neurodegenerative vulnerability.

Humans↗

PubMed2024

Contribution of copy number variations to education, socioeconomic status and cognition from a genome-wide study of 305,401 subjects.

Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31, and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb), and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders. Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.

Humans↗

PubMed2026

Pan-cancer Bioinformatics Analysis Combined with Colon Cancer Experimental Validation: A Study on TMED3 as a Diagnostic and Prognostic Biomarker.

Transmembrane Emp24 Protein Transport Domain 3 (TMED3), a member of the p24 protein family, has been implicated in tumor proliferation, invasion, and migration. This study aimed to evaluate the expression patterns, prognostic significance, immune associations, and potential biological functions of TMED3 across multiple cancer types using pan-cancer bioinformatics analysis combined with immunohistochemical (IHC) validation in colon cancer. Multiomics datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, UALCAN, Human Protein Atlas, and cBioPortal databases were analyzed to investigate TMED3 expression and genetic alterations in pan-cancer. Immunohistochemistry was performed to evaluate TMED3 protein expression in colon cancer tissues. Kaplan-Meier survival analysis and Cox regression analysis were used to assess the prognostic value of TMED3. Spearman correlation analysis was conducted to evaluate the associations of TMED3 with tumor mutational burden, microsatellite instability (MSI), immune cell infiltration, and immune checkpoints. Gene Set Enrichment Analysis was performed to investigate potential biological pathways associated with TMED3 in colon cancer. TMED3 expression was elevated in most tumor types and was associated with unfavorable overall survival and disease-specific survival in adrenocortical carcinoma, colon adenocarcinoma, and uveal melanoma. The greatest frequency of TMED3 genetic alterations was identified in mesothelioma, with amplification representing the predominant alteration type. In addition, TMED3 expression showed significant correlations with tumor mutational burden and microsatellite instability in kidney renal clear cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. TMED3 expression was also associated with immune infiltration and immune checkpoint expression in several tumors. IHC analysis demonstrated increased TMED3 expression in colon cancer tissues compared with normal colon tissues and showed an association with T stage. Functional enrichment analysis identified pathways related to ribosome, antigen processing and presentation, oxidative phosphorylation, and pentose phosphate. These findings indicate that TMED3 may represent a promising biomarker for the diagnosis and prognostic evaluation of colon cancer as well as other tumor types.

Humans↗