scholarly journals Proteomics in Melanoma Biomarker Discovery: Great Potential, Many Obstacles

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Michael S. Sabel ◽  
Yashu Liu ◽  
David M. Lubman
Keyword(s):  
Biomarker Discovery ◽  
Predictive Biomarkers ◽  
Clinical Staging ◽  
Fresh Tissue ◽  
Primary Tumors ◽  
Unique Challenge ◽  
Advantages And Disadvantages ◽  
Serum Proteomics ◽  
Therapeutic Decisions ◽  
Large Populations

The present clinical staging of melanoma stratifies patients into heterogeneous groups, resulting in the application of aggressive therapies to large populations, diluting impact and increasing toxicity. To move to a new era of therapeutic decisions based on highly specific tumor profiling, the discovery and validation of new prognostic and predictive biomarkers in melanoma is critical. Genomic profiling, which is showing promise in other solid tumors, requires fresh tissue from a large number of primary tumors, and thus faces a unique challenge in melanoma. For this and other reasons, proteomics appears to be an ideal choice for the discovery of new melanoma biomarkers. Several approaches to proteomics have been utilized in the search for clinically relevant biomarkers, but to date the results have been relatively limited. This article will review the present work using both tissue and serum proteomics in the search for melanoma biomarkers, highlighting both the relative advantages and disadvantages of each approach. In addition, we review several of the major obstacles that need to be overcome in order to advance the field.

Imaging Features of Primary Tumors of the Hand

2020 ◽  
Vol 16 ◽  
Author(s):  
Filippo Boriani ◽  
Edoardo Raposio ◽  
Costantino Errani
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Epithelioid Sarcoma ◽  
Case Series ◽  
Malignant Neoplasm ◽  
Benign Tumors ◽  
Imaging Features ◽  
Primary Tumors ◽  
Therapeutic Decisions ◽  
Tumors Of The Hand

: Musculoskeletal tumors of the hand are a rare entity and are divided into skeletal and soft tissue tumors. Either category comprises benign and malignant or even intermediate tumors. Basic radiology allows an optimal resolution of bone and related soft tissue areas, ultrasound and more sophisticated radiologic tools such as scintigraphy, CT and MRI allow a more accurate evaluation of tumor extent. Enchondroma is the most common benign tumor affecting bone, whereas chondrosarcoma is the most commonly represented malignant neoplasm localized to hand bones. In the soft tissues ganglions are the most common benign tumors and epithelioid sarcoma is the most frequently represented malignant tumor targeting hand soft tissues. The knowledge regarding diagnostic and therapeutic management of these tumors is often deriving from small case series, retrospective studies or even case reports. Evidences from prospective studies or controlled trials are limited and for this lack of clear and supported evidences data from the medical literature on the topic are controversial, in terms of demographics, clinical presentation, diagnosis prognosis and therapy.The correct recognition of the specific subtype and extension of the tumor through first line and second line radiology is essential for the surgeon, in order to effectively direct the therapeutic decisions.

scholarly journals The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Ekaterina Bourova-Flin ◽  
Samira Derakhshan ◽  
Afsaneh Goudarzi ◽  
Tao Wang ◽  
Anne-Laure Vitte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Specific Gene ◽  
Specific Expression ◽  
Intrinsic Nature ◽  
Independent Cohort

Abstract Background Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

scholarly journals L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Marc R. McCann ◽  
Mery Vet George De la Rosa ◽  
Gus R. Rosania ◽  
Kathleen A. Stringer
Keyword(s):  
Precision Medicine ◽  
Inborn Errors Of Metabolism ◽  
Clinical Utility ◽  
Biomarker Discovery ◽  
Genetic Disorders ◽  
Acid Oxidation ◽  
Inborn Errors ◽  
Therapeutic Decisions ◽  
Literature Evidence ◽  
Clinical Biomarker

Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.

scholarly journals MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Primary Tumors ◽  
Distant Tissue ◽  
Significant Expression ◽  
Metastatic Sites

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

scholarly journals Next-Generation Biomarkers for Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3222
Author(s):  
Pedro M. Rodrigues ◽  
Arndt Vogel ◽  
Marco Arrese ◽  
Domingo C. Balderramo ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Tumor Development ◽  
Predictive Biomarkers ◽  
Disease Diagnosis ◽  
Future Research ◽  
Tumor Biopsy ◽  
Non Invasive ◽  
Tumor Stages ◽  
At Risk Populations ◽  
Early Tumor

The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.

Angiogenic and T-effector subgroups identified by gene expression profiling (GEP) and propensity for PBRM1 and BAP1 alterations in clear cell renal cell carcinoma (ccRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 343-343
Author(s):  
Pedro C. Barata ◽  
Shuchi Gulati ◽  
Andrew Elliott ◽  
Arpit Rao ◽  
Hans J. Hammers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Hierarchical Clustering ◽  
Immune Cell ◽  
Expression Profiles ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Primary Tumors ◽  
Metastatic Sites ◽  
Patient Subgroups

343 Background: With the emergence of multiple active treatment options in RCC, predictive biomarkers for optimal treatment selection are lacking. Gene expression data from IMmotion151 and Javelin Renal 101 clinical trials generated anti-angiogenic and immune signatures that warrant further validation. We aimed to describe the genomic and gene expression profiles in a multi-institutional database of patients with ccRCC, and its association with other biomarkers of interest. Methods: Whole transcriptome sequencing was performed for ccRCC patient samples submitted to a commercial CLIA-certified laboratory (Caris Life Sciences, Phoenix, AZ) from February 2019 to September 2020. Tumor GEP and hierarchical clustering based on the validated 66-gene signature (D’Costa et al, 2020) were used to identify patient subgroups. Samples from both primary tumors and metastatic sites were included. Results: A total of 316 patients with ccRCC, median age 62 (range 32-90), 71.8% men, were included. Tissue samples were obtained from primary tumor (46.5%), lung (12.3%), bone (9.5%), liver (4.7%) and other metastatic sites (27%). Gene expression analysis identified angiogenic, mixed and T-effector subgroups in 24.1%, 51.3% and 24.7%, respectively. Patients with angiogenic subgroup tumors compared to those with T-effector subgroup tumors were more likely to be older (63 versus 60 years, p=0.035), female (40.8% versus 16.7%, p=0.0009) and more frequently found in pancreatic/small bowel metastases (75% versus 12.5%, p=0.0103). Biomarkers of potential response to immunotherapy such as PD-L1 (p=0.0021), TMB (not significant), and dMMR/MSI-H status (not significant) were more frequent in the T-effector subgroup. PBRM1 mutations were more common in the angiogenic subgroup (62.0% vs 37.5%, p=0.0034) while BAP1 mutations were more common in the T-effector subgroup (18.6% versus 3.0%, p= 0.0035). Immune cell population abundance (e.g. NK cells, monocytes) and immune checkpoint gene expression (TIM-3, PD-L1, PD-L2, CTLA4) were also increased in the T-effector subgroup. Conclusions: Our hierarchical clustering results based on the 66-gene expression signature were concordant with results from prior studies. Patient subgroups identified by evaluation of angiogenic and T-effector signature scores exhibit significantly different mutations and immune profiles. These findings require prospective validation in future biomarker-selected clinical trials.

scholarly journals Update Regarding Imaging of Neuroendocrine Neoplasms

2019 ◽  
Vol 192 (02) ◽  
pp. 171-182
Author(s):  
Jens Holger Figiel ◽  
Simon G. Viniol ◽  
Jannis Görlach ◽  
Anja Rinke ◽  
Damiano Librizzi ◽  
...  
Keyword(s):  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Primary Tumors ◽  
Advantages And Disadvantages ◽  
Key Points ◽  
Wide Range ◽  
Small Primary ◽  
Noninvasive Therapy ◽  
Spectrum Of Indications

Background Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors characterized by the expression of typical proteins. A wide range of morphological and functional imaging methods is required in order to adequately assess the course of the disease and to optimally treat the patient. The spectrum of indications ranges from the detection of small primary tumors to the documentation of the metastasis pattern and the assessment of the suitability for certain invasive or noninvasive therapy methods. The exact recording and quantification of findings is indispensable. Methods This article is based on a comprehensive literature search on the different aspects of neuroendocrine neoplasm imaging. Results This article is intended to provide an overview of the available imaging procedures with their respective advantages and disadvantages for diagnostics and their value for the follow-up of neuroendocrine neoplasms. Recommendations for examination protocols, typical image findings, and an outlook regarding future developments are presented. Key Points:  Citation Format

scholarly journals 240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A258-A258
Author(s):  
Myrto Moutafi ◽  
Sandra Martinez-Morilla ◽  
Prajan Divakar ◽  
Ioannis Vathiotis ◽  
Niki Gavrielatou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Biomarker Discovery ◽  
Univariate Analysis ◽  
Predictive Biomarkers ◽  
Protein Detection ◽  
Statistical Testing ◽  
Multiple Testing Correction ◽  
Stromal Compartment ◽  
Pre Treatment

BackgroundDespite the clinical effectiveness of Immune Checkpoint Inhibitors (ICI) in lung cancer, only around 20% remain disease free at 5 years. Predictive biomarkers for ICIs are neither sensitive nor specific. Here, we used the GeoMx Digital Spatial Profiler (DSP) (NanoString, Inc.) to analyze high-plex protein in a quantitative and spatially resolved manner from single formalin-fixed paraffin embedded tissue sections toward the goal of identification of new biomarkers with better predictive value.MethodsPre-treatment samples from 56 patients with NSCLC treated with ICI were collected, represented in Yale tissue microarray 471 (YTMA471), and analyzed. A panel of 71 photocleavable oligonucleotide-labeled primary antibodies (NanoString Human IO panel) was used for protein detection. Protein expression was measured in 4 molecularly defined tissue compartments, defined by fluorescence co-localization (tumor [panCK+], leukocytes [CD45+/CD68-], macrophages [CD68+] and an aggregate stromal immune cell compartment, defined as the sum of leukocyte and macrophage expression [panCK-/CD45+/CD68+]) generating 284 variables representing potential predictive biomarkers. Promising candidates were orthogonally validated with Quantitative Immunofluorescence (QIF). Pre-treatment samples from 40 patients with NSCLC (YTMA404) that received ICI, and 174 non-ICI treated operable NSCLC patients (YTMA423) were analyzed to provide independent cohort validation. All statistical testing was performed using a two-sided significance level of α=0.05 and multiple testing correction (Benjamini-Hochberg method, FDR < 0.1).ResultsInitial biomarker discovery on 284 protein variables were generated by univariate analysis using continuous log-scaled data. High PD-L1 expression in tumor cells predicted longer survival (PFS; HR 0.67, p=0.017) and validated the training cohort. We found 4 markers associated with PFS, and 3 with OS in the stromal compartment. Of these, expression of CD66b in stromal immune cells predicted significantly shorter OS (HR 1.31, p=0.016) and shorter PFS (HR 1.24, p = 0.04). Tertile analysis using QIF on all three tissue cohorts for CD66b expression, assessed by QIF, showed that CD66b was indicative but not prognostic for survival [discovery cohort, YTMA471 (OS; HR 3.02, p=0.013, PFS; HR 2.38, p=0.023), validation cohort; YTMA404 (OS; HR 2.97, p=0.018, PFS; HR 1.85, p=0.1), non-ICI treated cohort YTMA423 (OS; HR 1.02, p>0.9, PFS; HR 0.72, p=0.4)].ConclusionsUsing the DSP technique, we have discovered that CD66b expressed in the stromal immune [panCK-/CD45+/CD68+] molecular compartment is associated with resistance to ICI therapy in NSCLC. This observation was validated by an orthogonal approach in an independent ICI treated NSCLC cohort. Since CD66b identifies neutrophils, further studies are warranted to characterize the role of neutrophils in ICI resistance.AcknowledgementsDr Moutafi is supported by a scholarship from the Hellenic Society of Medical Oncologists (HESMO)Ethics ApprovalAll tissue samples were collected and used under the approval from the Yale Human Investigation Committee protocol #9505008219 with an assurance filed with and approved by the U.S. Department of Health and Human Services

scholarly journals Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

2020 ◽  
Vol 8 (5) ◽  
pp. 745
Author(s):  
Rafaela de Sousa Gonçalves ◽  
Flaviane Alves de Pinho ◽  
Ricardo Jorge Dinis-Oliveira ◽  
Rui Azevedo ◽  
Joana Gaifem ◽  
...  
Keyword(s):  
Treatment Group ◽  
Animal Health ◽  
Early Period ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Parasite Load ◽  
Response To Therapy ◽  
Canine Leishmaniasis ◽  
Th2 Response ◽  
Therapeutic Decisions

Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient’s prognosis.

Plasma/serum proteomics: depletion strategies for reducing high-abundance proteins for biomarker discovery

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1799-1812 ◽  
Author(s):  
Pey Yee Lee ◽  
Junaida Osman ◽  
Teck Yew Low ◽  
Rahman Jamal
Keyword(s):  
Biomarker Discovery ◽  
Dynamic Range ◽  
High Abundance ◽  
Future Perspectives ◽  
Proteomics Analysis ◽  
Wide Dynamic Range ◽  
Serum Proteomics ◽  
Detection And Identification ◽  
Potential Biomarkers ◽  
Abundance Proteins

Plasma and serum are widely used for proteomics-based biomarker discovery. However, analysis of these biofluids is highly challenging due to the complexity and wide dynamic range of their proteomes. Notably, highly abundant proteins tend to obscure the detection of potential biomarkers that are usually of lower concentrations. Among the strategies to resolve this problem are: depletion of high-abundance proteins, enrichment of low abundant proteins of interest and prefractionation. In this review, we focus on current and emerging depletion techniques used to enhance the detection and identification of the less abundant proteins in plasma and serum. We discuss the applications and contributions of these methods to proteomics analysis of plasma and serum alongside their limitations and future perspectives.

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