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PubMed2001

Proteomic approaches to biomarker discovery in prostate and bladder cancers.

Proteomic technologies, including high resolution two-dimensional electrophoresis (2-DE), antibody/protein arrays, and advances in mass spectrometry (MS), are providing the tools needed to discover and identify disease associated biomarkers. Although application of these technologies to search for potential diagnostic/prognostic biomarkers associated with prostate and bladder cancer have been somewhat limited to date, proteins either overexpressed or underexpressed have been detected in both these urological cancers. Recent advances in mass spectrometry, especially platforms that permit rapid "fingerprint" profiling of multiple biomarkers, and tandem mass spectrometers for protein identification, will most assuredly enhance the discovery, identification, and characterization of potential cancer associated biomarkers. Furthermore, application of laser capture microdissection microscopes has provided a rapid and reproducible approach to procure pure populations of cells. This technology coupled to 2-DE and MS has significantly aided the elucidation of the differential expression profiles between disease, benign and normal prostate and bladder cell populations. Finally, development and application of learning algorithms and bioinformatics to the data generated by these proteomic technologies will be essential in determining the clinical potential of a protein biomarker. The purpose of this review is to provide the reader with an overview of the application of these technologies in the search and identification of potential diagnostic/prognostic biomarkers for prostate and bladder cancers.

Biomarkers, Tumor↗

PubMed2025

Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome.

PURPOSE: Fetal alcohol spectrum disorder (FASD) encompasses a range of clinical features and neurodevelopmental disorders in children exposed to alcohol in utero. Despite its global public health significance, FASD diagnosis remains challenging because of nonspecific clinical findings and the lack of an accurate molecular diagnostic biomarker. This study aimed to evaluate peripheral blood DNA methylation (DNAm) profiles as a potential diagnostic biomarker for fetal alcohol syndrome. METHODS: Genomic DNAm profiles from 93 individuals with suspected or confirmed FAS, including a clinically diagnosed FAS subgroup, were analyzed and compared with a large database of control and patient cohorts with previously reported DNAm episignatures. Functional analysis of these DNAm profiles was performed to identify episignatures and assess their potential diagnostic utility. RESULTS: A relatively sensitive and specific DNAm episignature for FAS was identified. Comparative epigenomic analysis revealed functional correlations between FAS and other rare genetic disorders, supporting the robustness of the identified DNAm profiles as a diagnostic tool. CONCLUSION: This study demonstrates that unique DNAm profiles provide a robust episignature biomarker for FAS. These findings contribute to the molecular understanding of FAS and hold promise for improving diagnostic accuracy for this complex disorder.

Humans↗

PubMed2025

Impact of sodium-glucose cotransporter-2 inhibitors on aging biomarkers and plasma ceramide levels in type 2 diabetes: beyond glycemic control.

BACKGROUND: Aging is a complex biological process marked by the decline of physiological functions and heightened susceptibility to chronic illnesses, notably cardiometabolic disorders. Ceramides (Cer) are lipid derivatives linked to aging and metabolic diseases. Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), widely used in managing type 2 diabetes, have an unclear impact on aging biomarkers and Cer profiles. OBJECTIVE: This study explored the association between SGLT2i use, plasma Cer levels (CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1), and aging biomarkers-Human Insulin-Like Growth Factor 1 (IGF-1), mammalian target of rapamycin (mTOR), 5-Methylcytosine (5MC), and Human H2AFX (Histone H2AX) in patients with type 2 diabetes mellitus (T2DM). METHODS: In this retrospective study, 95 participants were divided into three groups: patients on SGLT2i (n = 34), patients on non-SGLT2i anti-diabetic treatments (n = 36), and healthy controls (n = 25). Plasma Cer and aging biomarkers were quantified using Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) and ELISA, respectively. Principal component analysis (PCA) assessed group-based clustering, while ANCOVA evaluated group differences with confounder adjustment. RESULTS: SGLT2i-treated patients showed significantly lower CerC16:0, CerC22:0, and CerC24:1 levels (p < 0.01) and decreased 5MC and H2AX (p < 0.05) compared to non-SGLT2i patients. IGF-1 was significantly elevated in the SGLT2i group (p < 0.01), suggesting a possible protective effect on metabolic health. PCA distinguished control from diabetic groups but revealed overlap between SGLT2i and non-SGLT2i groups. CONCLUSION: Beyond glucose control, SGLT2i may improve plasma Cer and aging markers in diabetic patients, supporting their broader therapeutic potential in aging and age-related diseases. Further large-scale studies are warranted to confirm these effects and underlying mechanisms.

Humans↗

PubMedDate not supplied

The evolving role of proteomics in the early detection of breast cancer.

There has been emerging interest in the examination of tumor protein expression (proteomics) as a means to identify novel diagnostic and therapeutic targets in women with breast cancer. Specifically, several investigators have examined biological fluids (serum and breast ductal fluid) and breast tissue in an attempt to detect novel proteomic profiles in women with breast carcinoma. The current tools of proteomic research are evolving, but include two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Initial studies have identified several unique biomarkers and proteomic profiles that were able to discriminate between non-cancer and breast cancer patients. In the future, the application of large-scale proteomic technology may provide a means of early detection, surveillance, and identification of potential therapeutic targets.

Biomarkers, Tumor↗

PubMed2005

Many accurate small-discriminatory feature subsets exist in microarray transcript data: biomarker discovery.

BACKGROUND: Molecular profiling generates abundance measurements for thousands of gene transcripts in biological samples such as normal and tumor tissues (data points). Given such two-class high-dimensional data, many methods have been proposed for classifying data points into one of the two classes. However, finding very small sets of features able to correctly classify the data is problematic as the fundamental mathematical proposition is hard. Existing methods can find "small" feature sets, but give no hint how close this is to the true minimum size. Without fundamental mathematical advances, finding true minimum-size sets will remain elusive, and more importantly for the microarray community there will be no methods for finding them. RESULTS: We use the brute force approach of exhaustive search through all genes, gene pairs (and for some data sets gene triples). Each unique gene combination is analyzed with a few-parameter linear-hyperplane classification method looking for those combinations that form training error-free classifiers. All 10 published data sets studied are found to contain predictive small feature sets. Four contain thousands of gene pairs and 6 have single genes that perfectly discriminate. CONCLUSION: This technique discovered small sets of genes (3 or less) in published data that form accurate classifiers, yet were not reported in the prior publications. This could be a common characteristic of microarray data, thus making looking for them worth the computational cost. Such small gene sets could indicate biomarkers and portend simple medical diagnostic tests. We recommend checking for small gene sets routinely. We find 4 gene pairs and many gene triples in the large hepatocellular carcinoma (HCC, Liver cancer) data set of Chen et al. The key component of these is the "placental gene of unknown function", PLAC8. Our HMM modeling indicates PLAC8 might have a domain like part of lP59's crystal structure (a Non-Covalent Endonuclease lii-Dna Complex). The previously identified HCC biomarker gene, glypican 3 (GPC3), is part of an accurate gene triple involving MT1E and ARHE. We also find small gene sets that distinguish leukemia subtypes in the large pediatric acute lymphoblastic leukemia cancer set of Yeoh et al.

Biomarkers↗

PubMed2026

Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) combined with endocrine therapy have become a therapeutic backbone for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, yet durable disease control is frequently limited by intrinsic and acquired resistance. Canonical tumor-cell mechanisms, including retinoblastoma-pathway escape, cyclin E-cyclin-dependent kinase 2 (CDK2) activation, endocrine adaptation, and phosphoinositide 3-kinase (PI3K)-AKT-mechanistic target of rapamycin (mTOR) signaling, explain only part of this failure because they do not fully capture dynamic immune and stromal remodeling. Preclinical and translational studies indicate that early CDK4/6 inhibition can enhance antigen presentation, activate interferon-related programs, restrain regulatory T cells, and promote a T-cell-inflamed state. These effects are conditional and may not persist during prolonged treatment. Sustained therapy can instead drive heterogeneous resistant niches characterized by stromal remodeling, myeloid recruitment, checkpoint adaptation, and T-cell dysfunction. This immune-state dependence provides a rationale for immune checkpoint blockade, although clinical combinations have shown mixed efficacy and clinically relevant hepatic, pulmonary, and hematologic toxicities. Sequential or lead-in strategies therefore warrant prospective evaluation. Oxidative phosphorylation (OXPHOS) and redox adaptation may sustain selected resistant states and expose context-dependent ferroptotic vulnerabilities. Ferroptosis may connect tumor-cell killing with immune regulation, whereas nanomedicine may improve tumor-selective delivery. Both strategies remain largely preclinical and require further evaluation of pharmacokinetics, biodistribution, toxicity, manufacturability, and immune-cell safety. This Review distinguishes intrinsic from acquired resistance across interpatient, intratumoral, spatial, and temporal dimensions. It integrates tumor-cell escape with cytokine, immune, stromal, vascular, and metabolic remodeling and summarizes emerging therapeutic strategies. We further propose a candidate biomarker-informed framework that integrates genomic profiling, spatial immune architecture, circulating biomarkers, T-cell receptor (TCR) dynamics, transcriptomic and single-cell analyses, artificial intelligence (AI)-assisted multimodal integration, and longitudinal sampling. This framework is intended to support biomarker development and prospective trial design rather than current clinical decision-making, providing a translational basis for testing state-informed and sequence-aware therapeutic strategies.

Humans↗

PubMed2002

Aerobic biodegradation of hopanes and other biomarkers by crude oil-degrading enrichment cultures.

The degradation of petroleum biomarkers was examined using mixed cultures of microorganisms enriched from surface soils at four different hydrocarbon-contaminated sites. These cultures degraded C30 17alpha(H),21beta(H)-hopane and the C31-C34 extended hopanes in Bonny Light crude oil after 21 days of incubation at 30 degrees C. The C35 extended hopanes were conserved, and no 25-norhopanes were detected during the incubation. Denaturing gradient gel electrophoresis (DGGE) analysis of the enrichment cultures demonstrated distinct microbial community profiles. Additional studies with the LC culture demonstrated a consistent biomarker degradation pattern after growth on three crude oils: a Nigerian Bonny Light crude, a Venezuelan crude oil, and Alaskan North Slope 521. The onset of biomarker degradation was observed between days 14 and 21 but only at 30 degrees C and at oil concentrations below 6 mg/mL. The biomarker profiles following degradation by these enrichment cultures are similar to numerous field observations and may represent the dominant biodegradation pattern found in many hydrocarbon-contaminated aerobic surface environments.

Bacteria, Aerobic↗

PubMed2005

Novel biomarkers of human growth hormone action from serum proteomic profiling using protein chip mass spectrometry.

CONTEXT: The detection of exogenous human GH (hGH) administration in athletes poses unique analytical problems, because its short circulating half-life provides only a brief opportunity to detect the administered hormone above endogenous levels. Measurement of novel GH-regulated serum protein biomarkers might provide an indirect method to detect exogenous GH. OBJECTIVE: The objective of this study was to identify new serum biomarkers of GH administration using proteomic profiling. DESIGN: Sera from a previously reported, double-blind, placebo-controlled GH administration trial were analyzed by protein chip mass spectrometry. SETTING: The study was performed at clinical research centers. SUBJECTS: Sixty healthy subjects, aged 18-40 yr, who were not elite athletes, were studied. INTERVENTIONS: Placebo or recombinant hGH treatment (0.1 or 0.2 IU/kg.d; 20 subjects/group) was administered for 4 wk, followed by an 8-wk washout period. MAIN OUTCOME MEASURES: Protein mass profiles were determined on immobilized Cu(2+) chips on d 0 and 21 of GH administration, and multivariate analysis was used to classify subjects into GH and placebo administration groups. RESULTS: When assessed by cross-validation, the classification performance of classifiers based on multivariate analysis of several GH-regulated peaks performed no better than classifiers based on the single best peak. This peak, a prominent biomarker of 15.1 kDa, was purified and identified as hemoglobin alpha-chain. The time course of the GH response of this biomarker is similar to that of other GH-dependent markers, such as IGF-I. CONCLUSION: This study demonstrates that protein mass profiling is an effective tool for the detection of GH administration and suggests that measurement of hemoglobin alpha-chain may have utility as a novel serum biomarker of GH action.

Adolescent↗

PubMed1996

Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity.

Changes in urinary porphyrin excretion patterns (porphyrin profiles) have been described in response to a variety of drugs and chemicals. The present studies were conducted to define the specific changes in the urinary porphyrin profile associated with prolonged exposure to mercury and mercury compounds. In rats, exposure for a prolonged period to mercury as methyl mercury hydroxide was associated with urinary porphyrin changes, which were uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins and by the expression of an atypical porphyrin ("precoproporphyrin") not found in urine of unexposed animals. These distinct changes in urinary porphyrin concentrations were observed as early as 1-2 weeks after initiation of mercury exposure, and increased in a dose- and time-related fashion with the concentration of mercury in the kidney, a principal target organ of mercury compounds. Following cessation of mercury exposure, urinary porphyrin concentrations reverted to normal levels, consistent with renal mercury clearance. In human studies, a comparable change in the urinary porphyrin profile was observed among subjects with occupational exposure to mercury as mercury vapor sufficient to elicit urinary mercury levels greater than 20 micrograms/L. Urinary porphyrin profiles were also shown to correlate significantly with mercury body burden and with specific neurobehavioral deficits associated with low level mercury exposure. These findings support the utility of urinary porphyrin profiles as a useful biomarker of mercury exposure and potential health effects in human subjects.

Adult↗

PubMed2004

The differential proteome profile of stomach cancer: identification of the biomarker candidates.

By comparative proteome analysis we searched for characteristic alterations of human stomach adenocarcinoma tissue and paired surrounding normal tissue. Selected differential protein spots were identified with peptide mass fingerprinting based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and database searching. We identified protein alterations in 18 stomach cancer tissues compared with normal controls, comprising elevated levels of eight proteins, including 14-3-3 zeta, calcyclin, keratin, apolipoprotein A-1 precursor, proteasome activator complex subunit, nucleoside diphosphate kinase, nicotinamide N-methyltransferase, and pyridoxal kinase. Five proteins (CA11, prohibitin, peroxiredoxin 4, serum amyloid P component, and NADH-ubiquinone oxidoreductase 23 kDa subunit) were decreased. These data are valuable for identification of differentially expressed proteins involved in stomach cancer carcinogenesis, providing biomarker candidates to develop diagnostic and therapeutic tools.

Adult↗

PubMed2002

Biomarkers of toluene diisocyanate exposure.

Biomarkers are very useful tools when the metabolic fate of the compound or the etiology of a resultant disease is completely understood. They may contribute to confusion if it is not possible to distinguish between markers of exposure and markers of disease. Such is the case for biomarkers used in the assessment of diisocyanate exposure. Biomarkers for diisocyanate exposure result from both direct and indirect effects. Molecules such as hemoglobin, albumin, tubulin, glutathione, and laminin have been implicated as having been directly modified as a result of exposure to toluene diisocyanate (TDI). In addition, indirect biomarkers have included profiles of molecules such as antibodies, cytokines, cell accumulation or proliferation, and markers of oxidative stress. While a brief presentation of each of these markers is provided here, the focus is primarily on immunological markers as an example of the difficulties with using biomarkers in assessing diisocyanate exposure in general, and TDI specifically. Compiled data will be used to demonstrate where gaps exist in our understanding of how the results of measured biomarkers are used with regard to isocyanate exposure, and whether it may be possible to develop these tools to define thresholds between exposure and disease. Issues addressed include whether the marker represents a measure of exposure or disease, whether the methods are sufficiently uniform between labs to be able to compare between studies, and whether the ambiguities are the result of the complexity of the isocyanate reactivity in the biological system, or our inability to accurately measure the end point of the reactions.

Air Pollutants, Occupational↗

PubMed2002

Biomarkers, yesterday, today and tomorrow: the basis for health claims.

The development of useful and accurate biomarkers for predicting outcomes of food based interventions is becoming more and more important, given the emphasis being placed on ingredients in foods contributing to disease risk reduction and optimal health promotion. With the human genome now laid bare, opportunities abound to barcode individuals with their risk profiles. The massive increase in DNA sequence information together with the development of new technologies such as genomics, proteomics and bioinformatics, has resulted in a much greater capacity to determine individual risk profiles. Screening for biomarkers at the gene or protein expression level using microarray technology has the potential to identify new biomarkers for disease diagnosis. Whether these techniques will enable a better understanding of food-gene interactions to permit health claims rather than better therapeutic treatment (at high economic cost) remains to be demonstrated.

Biomarkers↗

PubMedDate not supplied

Quest for novel cardiovascular biomarkers by proteomic analysis.

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.

Arteriosclerosis↗

PubMed2002

alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer.

CONTEXT: Molecular profiling of prostate cancer has led to the identification of candidate biomarkers and regulatory genes. Discoveries from these genome-scale approaches may have applicability in the analysis of diagnostic prostate specimens. OBJECTIVES: To determine the expression and clinical utility of alpha-methylacyl coenzyme A racemase (AMACR), a gene identified as being overexpressed in prostate cancer by global profiling strategies. DESIGN: Four gene expression data sets from independent DNA microarray analyses were examined to identify genes expressed in prostate cancer (n = 128 specimens). A lead candidate gene, AMACR, was validated at the transcript level by reverse transcriptase polymerase chain reaction (RT-PCR) and at the protein level by immunoblot and immunohistochemical analysis. AMACR levels were examined using prostate cancer tissue microarrays in 342 samples representing different stages of prostate cancer progression. Protein expression was characterized as negative (score = 1), weak (2), moderate (3), or strong (4). Clinical utility of AMACR was evaluated using 94 prostate needle biopsy specimens. MAIN OUTCOME MEASURES: Messenger RNA transcript and protein levels of AMACR; sensitivity and specificity of AMACR as a tissue biomarker for prostate cancer in needle biopsy specimens. RESULTS: Three of 4 independent DNA microarray analyses (n = 128 specimens) revealed significant overexpression of AMACR in prostate cancer (P<.001). AMACR up-regulation in prostate cancer was confirmed by both RT-PCR and immunoblot analysis. Immunohistochemical analysis demonstrated an increased expression of AMACR in malignant prostate epithelia relative to benign epithelia. Tissue microarrays to assess AMACR expression in specimens consisting of benign prostate (n = 108 samples), atrophic prostate (n = 26), prostatic intraepithelial neoplasia (n = 75), localized prostate cancer (n = 116), and metastatic prostate cancer (n = 17) demonstrated mean AMACR protein staining intensity of 1.31 (95% confidence interval, 1.23-1.40), 2.33 (95% CI, 2.13-2.52), 2.67 (95% CI, 2.52-2.81), 3.20 (95% CI, 3.10-3.28), and 2.50 (95% CI, 2.20-2.80), respectively (P<.001). Pairwise comparisons demonstrated significant differences in staining intensity between clinically localized prostate cancer compared with benign prostate tissue, with mean expression scores of 3.2 and 1.3, respectively (mean difference, 1.9; 95% CI, 1.7-2.1; P<.001). Using moderate or strong staining intensity as positive (score = 3 or 4), evaluation of AMACR protein expression in 94 prostate needle biopsy specimens demonstrated 97% sensitivity and 100% specificity for detecting prostate cancer. CONCLUSIONS: AMACR was shown to be overexpressed in prostate cancer using independent experimental methods and prostate cancer specimens. AMACR may be useful in the interpretation of prostate needle biopsy specimens that are diagnostically challenging.

Biomarkers, Tumor↗

PubMed2004

Breast cancer chemoprevention phase I evaluation of biomarker modulation by arzoxifene, a third generation selective estrogen receptor modulator.

PURPOSE: Arzoxifene, a new selective estrogen receptor modulator with strong breast antiestrogen activity and absence of uterine agonist activity, was explored as a potential chemoprevention agent. We performed a multi-institutional evaluation of arzoxifene in women with newly diagnosed ductal carcinoma in situ or T1/T2 invasive cancer. EXPERIMENTAL DESIGN: In a Phase IA trial, 50 pre- or postmenopausal women were randomized to 10, 20, or 50 mg of arzoxifene daily in the interval between biopsy and re-excision or were enrolled as no-treatment controls. In a Phase IB trial, 76 postmenopausal women were randomized to 20 mg of arzoxifene versus matched placebo. Serum specimens collected at entry and at re-excision were assayed for various hormones and growth factors. Tissue from biopsies (estrogen receptor + and/or progesterone receptor +) and re-excision specimens was evaluated immunohistochemically for proliferation (Ki-67 by MIB-1 and proliferating cell nuclear antigen) and other biomarkers. RESULTS: In both trials, increases in serum sex hormone binding globulin were noted, as were decreases in insulin-like growth factor (IGF)-I and the IGF-I:IGF binding protein-3 ratio (P < 0.007 versus control/placebo). For 45 evaluable women in Phase IA, decreases in proliferation indices were more prevalent for arzoxifene (particularly 20 mg) than for controls. For 58 evaluable women in Phase IB, a decrease in estrogen receptor expression for arzoxifene was observed compared with no change with placebo (P = 0.0068). However, decreases in proliferation indices for arzoxifene were not statistically different from placebo, perhaps due to a confounding effect of stopping hormone replacement therapy before entry. CONCLUSION: Given the favorable side effect profile and the biomarker modulations reported here, arzoxifene remains a reasonable candidate for additional study as a breast cancer chemoprevention agent.

Anticarcinogenic Agents↗

PubMed2005

Towards the application of proteomics in renal disease diagnosis.

Proteomics is widely envisioned as playing a significant role in the translation of genomics to clinically useful applications, especially in the areas of diagnostics and prognostics. In the diagnosis and treatment of kidney disease, a major priority is the identification of disease-associated biomarkers. Proteomics, with its high-throughput and unbiased approach to the analysis of variations in protein expression patterns (actual phenotypic expression of genetic variation), promises to be the most suitable platform for biomarker discovery. Combining such classic analytical techniques as two-dimensional gel electrophoresis with more sophisticated techniques, such as MS, has enabled considerable progress to be made in cataloguing and quantifying proteins present in urine and various kidney tissue compartments in both normal and diseased physiological states. Despite these accomplishments, there remain a number of important challenges that will need to be addressed in order to pave the way for the universal acceptance of proteomics as a clinically relevant diagnostic tool. We discuss issues related to three such critical developmental tasks as follows: (i) completely defining the proteome in the various biological compartments (e.g. tissues, serum and urine) in both health and disease, which presents a major challenge given the dynamic range and complexity of such proteomes; (ii) achieving the routine ability to accurately and reproducibly quantify proteomic expression profiles; and (iii) developing diagnostic platforms that are readily applicable and technically feasible for use in the clinical setting that depend on the fruits of the preceding two tasks to profile multiple disease biomarkers.

Animals↗

PubMed2024

Exploring the prognostic landscape of oral squamous cell carcinoma through mitochondrial damage-related genes.

Oral squamous cell carcinoma (OSCC), the most prevalent form of oral cancer, poses significant challenges to the medical community due to its high recurrence rate and low survival rate. Mitochondrial Damage-Related Genes (MDGs) have been closely associated with the occurrence, metastasis, and progression of OSCC. Consequently, we constructed a prognostic model for OSCC based on MDGs and identified potential mitochondrial damage-related biomarkers. Gene expression profiles and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Differential analysis was conducted to identify MDGs associated with OSCC. COX analysis was employed to screen seven prognosis-related MDGs and build a prognostic prediction model for OSCC. Cases were categorized into low-risk or high-risk groups based on the optimal risk score threshold. Kaplan-Meier (KM) analysis revealed significant survival differences (P < 0.05). Additionally, the area under the ROC curve (AUC) for patient survival at 1 year, 3 years, and 5 years were 0.687, 0.704, and 0.70, respectively, indicating a high long-term predictive accuracy of the prognostic model. To enhance predictive accuracy, age, gender, risk score, and TN staging were incorporated into a nomogram and verified using calibration curves. Risk scoring based on MDGs was identified as a potential independent prognostic biomarker. Furthermore, BID and SLC25A20 were identified as two potential independent mitochondrial damage-related prognostic biomarkers, offering new therapeutic targets for OSCC.

Humans↗

PubMed2006

Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix.

Genome-wide microarray-based comparative genomic hybridization (array CGH) was used to identify common chromosomal alterations involved in cervical carcinogenesis as a first step towards the discovery of novel biomarkers. The genomic profiles of nine squamous cell carcinomas (SCCs) and seven adenocarcinomas (AdCAs), as well as four human papillomavirus (HPV)-immortalized keratinocyte cell lines, were assessed. On a genome-wide scale, SCCs showed significantly more gains than AdCAs. More specifically, there was a striking and highly significant difference between the two histological types for gain at 3q12.1-28, which was predominantly observed in SCC. Other frequent alterations included gains of 1q21.1-31.1 and 20q11.21-13.33, and losses of 11q22.3-25 and 13q14.3-21.33. Subsequent FISH analysis for hTR, located at 3q26, confirmed the presence of 3q gain in SCCs and HPV-immortalized cell lines. Fine mapping of chromosome 20q using multiplex ligation-dependent probe amplification (MLPA) showed copy number increases for a number of genes located at 20q11-q12, including DNMT3B and TOP1. For DNMT3B, this correlated with elevated mRNA expression in 79% of cases. In conclusion, the assessment of frequent genomic alterations resulted in the identification of potential novel biomarkers, which may ultimately enable a better risk stratification of high-risk (hr)-HPV-positive women.

Adenocarcinoma↗