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PubMed2006

Serum circulating human mRNA profiling and its utility for oral cancer detection.

PURPOSE: The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease. PATIENTS AND METHODS: Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35). Circulating RNA was isolated from serum and linearly amplified using T7 polymerase. Microarrays were applied for profiling transcriptome in serum from 10 cancer patients and controls. The differential gene expression was analyzed by combining the present calls, t tests, and fold-change statistics. Quantitative polymerase chain reaction (PCR) was used to validate the selected candidate RNA markers identified by microarray. Receiver operating characteristic curve and classification models were exploited to evaluate the diagnostic power of these markers for OSCC. RESULTS: Human serum circulating mRNAs were presented by reverse transcriptase PCR. Microarray identified 2,623 +/- 868 probes assigned present calls in OSCC (n = 10) versus 1,792 +/- 165 in healthy patients (n = 10), indicating a higher complexity of serum transciptome in OSCC patients (P = .002, Wilcoxon test). Three hundred thirty-five serum RNAs exhibited significantly differential expression level between the two groups (P < .05, t test; fold > or = 2). Five cancer-related gene transcripts were consistently validated by quantitative PCR on serum from OSCC patients (n = 32) and controls (n = 35). The best combination of biomarkers yielded a receiver operating characteristic curve value of 88%, sensitivity (91%), and specificity (71%) in distinguishing OSCC. CONCLUSION: The utility of serum transcriptome diagnostics is successfully demonstrated for OSCC detection. This novel concept could be developed as an adjunctive tool for disease diagnosis.

Biomarkers↗

PubMed2001

Effects of polychlorinated biphenyls on development and reproduction.

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article, which constitutes the release of an important section of the Toxicological Profile for Polychlorinated Biphenyls (ATSDR 2000) into the scientific literature, focuses on the developmental and reproductive effects of this group of synthetic organic chemicals (PCBs) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile. Interested readers are encouraged to consult the original toxicological profile for more information. Profiles can be requested from ATSDR's Information Center by telephone (1-888-42-ATSDR [1-888-422-8737] or E-mail: (atsdric@cdc.gov).

Animals↗

PubMed2002

Differential expression of SOX4 and SOX11 in medulloblastoma.

Primitive neuroectodermal tumors (PNETs) are composed of immature neuronal precursor cells and sometimes more mature neuronal cell types. Medulloblastomas, occuring in the cerebellum, represent the most common PNET and are broadly classified into two subgroups: classical and desmoplastic. Desmoplastic medulloblastomas exhibit a slightly better prognosis than classical medulloblastomas. However, there are currently no good molecular markers available to distinguish clinical outcome and similar treatment is used for most patients with associated complications. It has been shown that neoplastic cells in these tumors recapitulate stages in maturation of normal human neuroblasts; therefore, embryological studies of the earliest events in the development of the cerebellum may provide useful information about the molecular behavior of the tumor. Transcription factors such as Sox proteins involved in neural development may also play a role in the etiology of brain tumors. Sox4 in particular has been implicated in the biology of several other types of cancer. We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas. Sox4 and Sox11 were strongly expressed in most classical medulloblastomas but only weakly in desmoplastic medulloblastomas. The expression profile of these two genes in developing cerebellum was also analyzed. Our results suggest that strong Sox4 and Sox11 expression in classical medulloblastomas reflects their maturation-dependent expression during normal cerebellum development, and that they may therefore provide markers to divide tumors into clinically relevant subgroups.

Biomarkers, Tumor↗

PubMed2005

Conserved transcription factor binding sites of cancer markers derived from primary lung adenocarcinoma microarrays.

Gene transcription in a set of 49 human primary lung adenocarcinomas and 9 normal lung tissue samples was examined using Affymetrix GeneChip technology. A total of 3442 genes, called the set M AD, were found to be either up- or down-regulated by at least 2-fold between the two phenotypes. Genes assigned to a particular gene ontology term were found, in many cases, to be significantly unevenly distributed between the genes in and outside M AD. Terms that were overrepresented in M AD included functions directly implicated in the cancer cell metabolism. Based on their functional roles and expression profiles, genes in M AD were grouped into likely co-regulated gene sets. Highly conserved sequences in the 5 kb region upstream of the genes in these sets were identified with the motif discovery tool, MoDEL. Potential oncogenic transcription factors and their corresponding binding sites were identified in these conserved regions using the TRANSFAC 8.3 database. Several of the transcription factors identified in this study have been shown elsewhere to be involved in oncogenic processes. This study searched beyond phenotypic gene expression profiles in cancer cells, in order to identify the more important regulatory transcription factors that caused these aberrations in gene expression.

5' Flanking Region↗

PubMed2006

Evidence of a genomic biomarker in normal human epithelial mammary cell line, MCF-10A, that is absent in the human breast cancer cell line, MCF-7.

This study investigated the use of DNA amplification fingerprinting (DAF) to identify biomarkers useful in the elucidating genetic factors that lead to carcinogenesis. The DNA amplification fingerprinting (DAF) technique was used to generate fingerprint profiles of a normal human mammary epithelial cell line (MCF-10A) and a human breast cancer cell line (MCF-7). When compared with one another, a polymorphic biomarker gene (262 base pairs (bps)) was identified in MCF-10A but was not present in MCF-7. This gene was cloned from the genomic DNA of the MCF-10A cell line, and subjected to Genbank database analysis. The analysis of the nucleotide sequence polymorphic marker (Genbank account: AC079630) shows that this biomarker has 100% homology with the nucleotide sequence of human chromosome 12 BAC RP11-476D10 (bps 19612-19353). The nucleotide sequence was used for possible protein translation product and the result obtained indicated that the gene codes for hypothetical protein XF2620. In order to evaluate the effects that the 262 bps biomarker would have on the morphology of MCF-7 cells, it was transfected into MCF-7 cells. There were observable changes in the morphology of the transfected cells. These changes included an increase in cell elongation and a decrease in cell aggregation.

Journal Article↗

PubMed2007

Identification of the differential expressive tumor associated genes in rectal cancers by cDNA microarray.

AIM: To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors. METHODS: Rectal cancer tissues and their paired normal mucosa were obtained from patients undergoing surgical resection of rectal cancer. Total RNA was extracted using Trizol reagents. First strand cDNA synthesis was indirectly labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional ester. After normalization to total spots, the genes which background subtracted intensity did not exceed 2 SD above the mean blank were excluded. The data were then sorted to obtain genes differentially expressed by >or= 2 fold up or down in at least 5 of the 21 patients. RESULTS: In the 21 rectal cancer patients, 23 genes were up-regulated in at least 5 samples and 15 genes were down-regulated in at least 5 patients. Hierachical cluster analysis classified the patients into two groups according to the clinicopathological stage, with one group being all above stage II and one group all below stage II. CONCLUSION: The up-regulated genes and down-regulated genes may be molecular markers of rectal cancer. The expression profiles can be used for classification of rectal cancer.

Adenocarcinoma↗

PubMed2006

Gene expression profile of the adult human retinal ganglion cell layer.

PURPOSE: Pathophysiological events in the retinal ganglion cell layer (GCL) are a prominent feature of several optic neuropathies including glaucoma. The purpose of this study was to identify and catalog genes whose expression in the human retina is restricted to the GCL. METHODS: Laser capture microdissection (LCM) technology was used to isolate tissue from the perimacular retina of three human donors without retinal or optic nerve disease. RNA was isolated from the (1) retinal GCL and (2) the inner and outer nuclear layers of the same retina, and the gene expression profiles of both fractions were determined using Affymetrix Hu133Plus 2.0 GeneChips. Data were analyzed to identify those genes whose expression is substantially more prevalent in the GCL when compared to the outer retinal layers. Differential expression of selected genes was confirmed by real-time PCR and immunohistochemistry. RESULTS: The results show that mRNA levels of previously described ganglion cell markers, e.g. the neurofilament genes (NEFH, NEF3, or NEFL) and the Brn3a transcription factor (POU4F1), were highly enriched in the isolated GCL fraction. In contrast, transcripts for genes associated with phototransduction (RHO), photoreceptor development (NR2E3), or interphotoreceptor matrix constituents (IMPG1) were nearly absent from the GCL fraction. Using bioinformatics approaches over 80 genes were identified whose expression in the human retina appears to be limited to the GCL. CONCLUSIONS: We have successfully used LCM technology to generate gene expression profiles of highly enriched GCL fractions of the normal human retina. These data not only provide clues to the normal function of retinal ganglion cells but also serve as a resource in the development of ganglion cell specific markers or transfection vectors, and the identification of candidate genes for hereditary forms of glaucoma.

Aged↗

PubMed2004

Genes differentially expressed in prostate cancer.

Because of the heterogeneity of prostate cancer knowledge about the genes involved in prostate carcinogenesis is still very limited. Previously, the use of novel high-throughput technologies offered the possibility to investigate broad gene expression profiles and thus helped to improve understanding of the molecular basis of prostate disease. Many candidate genes have been identified so far which have a more or less strong effect on prostate cancer. This vast number of gene expression changes show that it is unlikely that only one gene promotes prostate cancer. Conversely, it seems more likely that a broad network of molecular changes is involved in the complex cascade of events which lead to tumour formation and progression, respectively. A few of these novel molecular targets are currently under clinical evaluation. This paper gives an overview of several interesting candidate genes which may be useful as improved biomarkers for diagnosis or as targets for developing novel treatment methods.

Biomarkers, Tumor↗

PubMed2026

Decoding protein signatures and protein interactions in oral potentially malignant disorders: a systematic review and network analysis.

BACKGROUND: Proteomic profiling offers thorough insights into protein structure and function, as well as it acts as an essential approach for analyzing molecular changes at the tissue level. However, because of the proteome's diversity and dynamic nature, biomarker discovery remains challenging. By combining proteomics with bioinformatics, the level of understanding in relation to molecular interactions and disease processes can be improved. Through an integrative approach, few limitations can be addressed, thereby promoting proteomic profiling for the discovery of new therapeutic targets and novel biomarkers for a variety of disorders. AIM: To identify differentially expressed protein markers and their key molecular pathways associated with Oral Potentially Malignant Disorders. METHODS: Systematic Review was conducted following the PRISMA guidelines and the protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration ID number CRD42024557545. A comprehensive literature review was performed using electronic databases, yielding 12,797, studies from which 15 eligible articles were selected. The Newcastle-Ottawa Scale was used to assess the risk of bias. Vote counting was performed to identify proteins reported in more than one study. A bipartite network was constructed using Cytoscape to identify shared and disease-specific protein markers. Lesion-wise protein-protein interaction networks were generated using STRING and analysed in Cytoscape to identify highly interconnected hub proteins, and pathway enrichment analysis for these hubs was performed using Reactome. RESULTS: A total of fifteen studies (Leukoplakia (LK) - n = 1, Proliferative Verrucous Leukoplakia (PVL) - n = 2, Oral Submucous Fibrosis (OSMF) - n = 7, and Oral Lichen Planus (OLP) - n = 5) were included. The Newcastle-Ottawa Scale was used to evaluate methodological quality and the quality of studies included in this systematic review was high for 4 articles and moderate in the remaining 11. The most commonly employed technique was mass spectrometry. A total of 318 candidate proteins (LK - 14, PVL - 82, OSMF - 172, and OLP - 50) were identified across the oral potentially malignant disorders. Key markers identified through vote counting included ERO1A, NUCB1, RHOA, and IL36A for PVL; LUM, KRT1, KRT9, ALB, and VIM for OSMF; and ALB, LYZ, HP, HBB, and AMY1A for OLP. The bipartite network showed that OSMF and OLP shared the highest number of proteins, indicating the strongest overlap among lesions. Network analysis further highlighted distinct hub proteins for each lesion: for LK- AMY1A, AMY1B and APOA1; for PVL- CFL1, RHOA and CDC42; for OSMF- HSP90AA1, ENO1 and SERPINA1; and for OLP- HP, B2M, and ORM1. Lesion-specific pathway enrichment revealed that LK was associated with epithelial differentiation, PVL with oncogenic signaling, OSMF with stress-driven fibrosis, and OLP with immune-mediated inflammation. CONCLUSIONS: Proteomic expression offers insights into disease pathogenesis by identifying important molecular changes across OPMDs. However, the majority of biomarkers are still in the exploratory stage due to the considerable variation in lesion types, sample sources, proteomic techniques, and reporting systems. In order to create reliable and clinically applicable biomarkers, future studies should concentrate on combining multi-omics techniques with large-scale, standardized cohorts.

Humans↗

PubMed2005

Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma.

Metastatic lesions occur in up to 36% of patients with pheochromocytoma. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytoma. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytoma pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytoma patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytoma pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease.

Adolescent↗

PubMed2003

Classification of bladder cancer by microarray expression profiling: towards a general clinical use of microarrays in cancer diagnostics.

At present there are no clinically useful markers available for identifying bladder cancer patients with a high risk of disease recurrence or progression. Thus, identification and tailor-suited treatment, for example radical cystectomy and adjuvant therapy, of patients with a poor prognosis is not possible using current methods. The completion of the Human Genome Project and the simultaneous advances in microarray technology have paved the way for performing systematic, full genome screens for prognostic and diagnostic molecular cancer markers. Furthermore, utilization of microarray technology for identifying clinically relevant subclasses of cancer patients and for discovering new potential drug targets seems promising. This article summarizes some of the clinical aspects of bladder cancer and reviews the potential of using tumor expression profiling for the identification of new molecular cancer markers and drug targets, and for generating disease classifiers and outcome predictors using several key gene markers.

Biomarkers, Tumor↗

PubMed2006

In vitro drug response and molecular markers associated with drug resistance in malignant gliomas.

PURPOSE: Drug resistance in malignant gliomas contributes to poor clinical outcomes. We determined the in vitro drug response profiles for 478 biopsy specimens from patients with the following malignant glial histologies: astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n = 259), oligodendroglioma (n = 40), and glioma (n = 69). EXPERIMENTAL DESIGN: Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan. Biomarkers associated with drug resistance were detected by immunohistochemistry, including multidrug resistance gene-1, glutathione S-transferase pi (GSTP1), O(6)-methylguanine-DNA methyltransferase (MGMT), and mutant p53. RESULTS: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance. CONCLUSIONS: Assessment of in vitro drug response and profiles of relevant tumor-associated biomarkers may assist the clinician in stratifying patient treatment regimens.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2006

Characterization of the outer membrane protein profile from disease-related Helicobacter pylori isolates by subcellular fractionation and nano-LC FT-ICR MS analysis.

Because of the important role of membrane proteins in adhesion, invasion, and intracellular survival of pathogens in the host, membrane proteins are of potential interest in the search for drug targets or biomarkers. We have established a mass spectrometry-based method that allows characterization of the outer membrane protein (OMP) profile of clinical isolates from of the human gastric pathogen Helicobacter pylori. Subcellular fractionation and one-dimensional gel electrophoresis (1D-GE) analysis was combined with nano-liquid chromatography Fourier transform-ion cyclotron resonance mass spectrometry (nano-LC FT-ICR MS) and tandem mass spectrometry (MS/MS) analysis of fifteen H. pylori strains associated either with duodenal ulcers, gastric cancer, or isolated from asymptomatic H. pylori infected carriers. Over 60 unique membrane or membrane-associated proteins, including 30 of the 33 theoretically predicted OMPs, were identified from the strains. Several membrane proteins, including Omp11 and BabA, were found to be expressed by all strains. In the search for clinical markers we found that Omp26 was expressed by all disease-related strains but was only present in one out of five strains from asymptomatic carriers, which makes Omp26 a potential target for further investigation in the search for proteins unique to disease-related H. pylori strains. In addition, presence of Omp30 and absence of Omp6 seemed to be associated with H. pylori strains causing duodenal ulcer.

Amino Acid Sequence↗

PubMed2003

Classification of follicular thyroid tumors by molecular signature: results of gene profiling.

PURPOSE: Thyroid nodules are common, with a lifetime risk of developing a clinically significant thyroid nodule of 10% or higher. Preoperative diagnosis was greatly enhanced by the introduction of fine needle aspiration in the 1970s, but there has been little advancement since that time. Discrimination between benign and malignant follicular neoplasms is currently not possible by fine needle aspiration and can even be difficult after full pathologic review. The purpose of these studies is to identify genes expressed in follicular adenomas and carcinomas of the thyroid that will permit molecular differentiation of these neoplasms. EXPERIMENTAL DESIGN: Gene expression patterns of 17 thyroid follicular tumors were analyzed by oligonucleotide array analysis. Gene profiles for follicular adenomas and carcinomas were identified, and the two groups were compared for differences in expression levels. The differentially expressed genes were used to perform a hierarchical clustering analysis training set. Five follicular tumors with diagnosis undisclosed to the investigators and 2 minimally invasive carcinomas were entered into the cluster analysis as a test set to determine whether diagnosis by gene profile correlated with that obtained by pathologic evaluation. RESULTS: Thyroid follicular adenomas and carcinomas showed strikingly distinct gene expression patterns. The expression patterns of 105 genes were found to be significantly different between follicular adenoma and carcinoma. Many uncharacterized genes contributed to the distinction between tumor types. For five follicular tumors for which the final diagnosis was undisclosed, the clustering algorithm gave the correct diagnosis in all 5 cases. CONCLUSIONS: Gene profiling is a useful tool to predict the molecular diagnosis of follicular thyroid tumors. Genes were identified that reliably differentiate follicular thyroid carcinoma from adenoma. This study provides insight into genes that may be important in the molecular pathogenesis of follicular thyroid tumors, as well candidates for preoperative diagnosis of follicular thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMed2004

Comparative proteomic analysis of de-N-glycosylated serum from hepatitis B carriers reveals polypeptides that correlate with disease status.

Analysis of the polypeptide profile in tissues, cells, and sera by high-resolution two-dimensional (2-D) gel electrophoresis offers promise in the identification of biomarkers that correlate with disease. However, sera contain many polypeptides bearing N-linked glycosylation that can complicate interpretation. Therefore, we tested the possibility that de-N-glycosylation of the polypeptides present in human serum would result in a simplification of serum proteome profiles. Briefly, polypeptides present in human serum were left untreated or subjected to de-N-glycosylation by incubation with PNGase F and resolved by high-resolution 2-D gel electrophoresis. De-N-glycosylation reduced the number of glycoform variants, enhanced the resolution of many polypeptides and allowed other polypeptides to become visible. As an initial test of concept, clinically relevant serum samples from individuals with or without diagnosis of hepatocellular carcinoma were compared. Several polypeptides, apparent only after de-N-glycosylation, were shown to correlate with disease. Although the results are preliminary and the identities of all the putative biomarkers not yet known, the data suggest that de-N-glycosylation offers a method to enhance the resolution of serum polypeptide profiles and has value in comparative proteomic studies.

Amyloid↗

PubMed2005

Overview of molecular, cellular, and genetic neurotoxicology.

It has become increasingly evident that the field of neurotoxicology is not only rapidly growing but also rapidly evolving, especially over the last 20 years. As the number of drugs and environmental and bacterial/viral agents with potential neurotoxic properties has grown, the need for additional testing has increased. Only recently has the technology advanced to a level that neurotoxicologic studies can be performed without operating in a "black box." Examination of the effects of agents that are suspected of being toxic can occur on the molecular (protein-protein), cellular (biomarkers, neuronal function), and genetic (polymorphisms) level. Together, these areas help to elucidate the potential toxic profiles of unknown (and in some cases, known) agents. The area of proteomics is one of the fastest growing areas in science and particularly applicable to neurotoxicology. Lubec et al, provide a review of the potential and limitations of proteomics. Proteomics focuses on a more comprehensive view of cellular proteins and provides considerably more information about the effects of toxins on the CNS. Proteomics can be classified into three different focuses: post-translational modification, protein-expression profiling, and protein-network mapping. Together, these methods represent a more complete and powerful image of protein modifications following potential toxin exposure. Cellular neurotoxicology involves many cellular processes including alterations in cellular energy homeostasis, ion homeostasis, intracellular signaling function, and neurotransmitter release, uptake, and storage. The greatest hurdle in cellular neurotoxicology has been the discovery of appropriate biomarkers that are reliable, reproducible, and easy to obtain. There are biomarkers of exposure effect, and susceptibility. Finding the appropriate biomarker for a particular toxin is a daunting task. The appropriate biomarker for a particular toxin is a daunting task. The advantage to biomarker/toxin combinations is they can be detected and measured shortly following exposure and before overt neuroanatomic damage or lesions. Intervention at this point, shortly following exposure, may prevent or at least attenuate further damage to the individual. The use of peripheral biomarkers to assess toxin damage in the CNS has numerous advantages: time-course analysis may be performed, ethical concerns with the use of human subjects can partially be avoided, procedures to acquire samples are less invasive, and in general, peripheral studies are easier to perform. Genetic neurotoxicology comprises two focuses--toxin-induced alterations in genetic expression and genetic alterations that affect toxin metabolism, distribution, and clearance. These differences can be beneficial or toxic. Polymorphisms have been shown to result in altered metabolism of certain toxins (paraoxonase and paraoxon). Conversely, it is possible that some polymorphisms may be beneficial and help prevent the formation of a toxic by-product of an exogenous agent (resistance to ozone-induced lung inflammation). It has also become clear that interactions of potential toxins are not straightforward as interactions with DNA, causing mutations. There are numerous agents that cause epigenetic responses (cellular alterations that are not mutagenic or cytotoxic). This finding suggests that many agents that may originally have been thought of as nontoxic should be re-examined for potential "indirect" toxicity. With the advancement of the human genome project and the development of a human genome map, the effects of potential toxins on single or multiple genes can be identified. Although collectively, the field of neurotoxicology has recently come a long way, it still has a long way to go reach its full potential. As technology and methodology advances continue and cooperation with other disciplines such as neuroscience, biochemistry, neurophysiology, and molecular biology is improved, the mechanisms of toxin action will be further elucidated. With this increased understanding will come improved clinical interventions to prevent neuronal damage following exposure to a toxin.

Animals↗

PubMed2026

Essence: A benchmarking-validated transformer framework for early diagnosis of Parkinson's disease using cerebrospinal fluid protein biomarkers.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The lack of objective molecular biomarkers limits early diagnosis and personalized treatment. Here, we propose Essence, a benchmarking-validated framework integrating cerebrospinal fluid (CSF) proteomics with traditional and deep learning models to identify robust protein signatures for PD. Using data from two independent cohorts, 1266 high-confidence proteins are quantified, among which 178 exhibit differential abundance between PD and healthy controls (HC). Through systematic benchmarking of ten machine learning algorithms and four neural architectures, the Transformer model consistently outperforms alternatives across multiple feature selection strategies, achieving an area under the receiver operating characteristic curve (AUC) of 1.0000 with only 35 features. Functional analyses of the top-ranked 35 proteins reveal enrichment in neuroinflammatory, synaptic, and oxidative stress-related pathways. Importantly, spatial transcriptomic profiling based on the Allen Brain Atlas shows region-specific expression of these biomarkers in PD-relevant brain structures, including the striatum, subthalamic nucleus, hippocampus, and white matter tracts. This anatomical alignment supports the functional relevance of the identified markers and highlights their potential utility in early-stage diagnosis and mechanistic understanding of PD.

Benchmarking↗

PubMed2004

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

Biomarkers, Tumor↗