Cancer Genomics & Proteomics[JOURNAL]
Sun
200 papers
Comparative proteomics uncovers vital molecular players of central nervous system leukemia among Mexican pediatric patients.
Ruiz-May E, Bojórquez-Velázquez E, Carrasco-Vargas H … +11 more , Soto-Alvarez S, Rangel-Cova LS, Vargas-Hernández MA, Elizalde-Contreras JM, Torres De La Cruz VM, Vilchis-Ordoñez A, Palomo-Colli MÁ, Floriano TA, Ortega IP, Pelayo-Camacho R, Huerta-Nuñez LFE
J Proteomics · 2025 Jun · PMID 40389027 · Publisher ↗
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. The leukemic cells start in the bone marrow and spread to other vital organs and tissues, including the central nervous system (CNS)...
Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. The leukemic cells start in the bone marrow and spread to other vital organs and tissues, including the central nervous system (CNS). Hispanic males are the community with the highest incidence of ALL. Unfortunately, there is limited information on the molecular signatures of leukemic cell infiltration into the CNS, which marks the progression from ALL to central nervous system leukemia (CNSL). To address this knowledge gap, we performed a label-free shotgun proteomics between the cerebrospinal fluid (CSF) from patients with ALL compared to those with confirmed CNSL. We were able to identify 619 proteins, including 340 proteins that had not been reported prevously in the CSF of subjects with CNSL. The major features associated with CNSL included the over-accumulation of cell-adhesion proteins such as L-selectin and several cadherin proteins, along with the modulation of enzymes associated with protein glycosylation, which may provide the appropriate conditions for leukemic cell infiltration into the CNS. The over-accumulation of proteins associated with ROS scavenging processes reveals hypoxic and redox homeostasis microenvironment conditions that favors ALL progression to CNSL. The further characterization of key differential proteins will be essential for establishing reliable molecular markers for CSNL. BIOLOGICAL SIGNIFICANCE: Central nervous system leukemia (CNSL) is a catastrophic progression of ALL defined by leukemic cells reaching the CNS. Limited comparative proteomics studies have been conducted previously between patients with ALL versus CNSL. While these studies were important pioneering steps, they were hindered by difficulties in obtaining the proper amount of protein samples related to CSF. They were based on minimal study subjects, and their proteomics pipelines did not include the depletion of high-abundance proteins. Defining the manners in which the CNSL proteome is perturbed compared to the ALL condition is paramount to understanding the molecular foundations of CNSL and identifying and characterizing protein markers for proper diagnosis. Improving the sensitivity and reliability of diagnosis using molecular markers would help clinicians to maximize patient outcomes and quality of life by implementing aggressive CNSL treatments as soon as possible in cases where infiltration has occurred, while avoiding exposure to toxic chemotherapies in patients where they are not yet necessary.
Comparative Analysis of the Progesterone Receptor Interactome in the Human Ovarian Granulosa Cell Line KGN and Other Female Reproductive Cells.
Foot NJ, Dinh DT, Emery-Corbin SJ … +3 more , Yousef JM, Dagley LF, Russell DL
Proteomics · 2025 Jul · PMID 40357704 · Full text
The nuclear steroid hormone receptor progesterone receptor (PGR) is expressed in granulosa cells in the ovarian follicle in a tightly regulated pattern in response to the surge of luteinizing hormone (LH) that stimulates...
The nuclear steroid hormone receptor progesterone receptor (PGR) is expressed in granulosa cells in the ovarian follicle in a tightly regulated pattern in response to the surge of luteinizing hormone (LH) that stimulates ovulation. PGR plays a critical role in mediating ovulation in response to LH, however, the mechanism for this is still unknown. We performed immunoprecipitation-mass spectrometry using the KGN human granulosa cell line expressing the primary PGR isoforms PGR-A or PGR-B, to identify novel interacting proteins that regulate PGR function in these ovary-specific target cells. Proteomic analysis revealed protein interactions with both PGR isoforms that were gained (e.g., transcriptional coactivators) or lost (e.g., chaperone proteins) in response to the PGR agonist R5020. Additionally, isoform-specific interactions, including different families of transcriptional regulators, were identified. Comparison with published datasets of PGR-interacting proteins in human breast cancer cell lines and decidualized endometrial stromal cells demonstrated a remarkable number of tissue-specific interactions, shedding light on how PGR can maintain diverse functions in different tissues. In conclusion, we provide a comprehensive novel dataset of the PGR interactome in previously unstudied ovarian cells and offer new insights into ovary-specific PGR transcriptional mechanisms.
Immobilized metal ion affinity chromatography: waltz of metal ions and biomacromolecules.
Yan R, Xu YM, Lau ATY
Expert Rev Proteomics · 2025 May · PMID 40249414 · Publisher ↗
INTRODUCTION: Immobilized metal ion affinity chromatography (IMAC) is an effective method developed in the 1980s for the separation and purification of proteins. The system consists of a solid-phase matrix, a linking lig...
INTRODUCTION: Immobilized metal ion affinity chromatography (IMAC) is an effective method developed in the 1980s for the separation and purification of proteins. The system consists of a solid-phase matrix, a linking ligand, and a metal ion. The method is based on the ability of metal ions to bind specifically to certain specific amino acid residues of proteins, thereby selectively enriching and purifying proteins. AREAS COVERED: This review aims to describe current knowledge of fundamental principle of IMAC and summarize the supports, chelating ligands, and metal ions of IMAC. In addition, how IMAC technology is used in proteomics and nucleic acids research are highlighted. EXPERT OPINION: Over the past decades, IMAC has been extensively utilized as a predominant technique for protein enrichment in a variety of biological and medical research, such as disease diagnosis, tumor biomarker identification, protein purification, and nucleic acids research. In the future, IMAC should be integrated with other emerging proteomics technologies to promote the applications of metalloproteomes in disease diagnosis, metallodrug development, and clinical translation.
Comprehensive biobanking strategy with clinical impact at the European Cancer Moonshot Lund Center.
Oskolas H, Nogueira FCN, Domont GB … +33 more , Yu KH, Semenov YR, Sorger P, Steinfelder E, Corps L, Schulz L, Wieslander E, Fenyö D, Kárpáti S, Holló P, Kemény LV, Döme B, Megyesfalvi Z, Pawłowski K, Nishimura T, Kwon H, Encarnación-Guevara S, Szasz AM, Veréb Z, Gyulai R, Németh IB, Appelqvist R, Rezeli M, Baldetorp B, Horvatovich P, Malmström J, Pla I, Sanchez A, Knudsen B, Kiss A, Malm J, Marko-Varga G, Gil J
J Proteomics · 2025 May · PMID 40246065 · Publisher ↗
This white paper presents a comprehensive biobanking framework developed at the European Cancer Moonshot Lund Center that merges rigorous sample handling, advanced automation, and multi-omic analyses to accelerate precis...
This white paper presents a comprehensive biobanking framework developed at the European Cancer Moonshot Lund Center that merges rigorous sample handling, advanced automation, and multi-omic analyses to accelerate precision oncology. Tumor and blood-based workflows, supported by automated fractionation systems and standardized protocols, ensure the collection of high-quality biospecimens suitable for proteomic, genomic, and metabolic studies. A robust informatics infrastructure, integrating LIMS, barcoding, and REDCap, supports end-to-end traceability and realtime data synchronization, thereby enriching each sample with critical clinical metadata. Proteogenomic integration lies at the core of this initiative, uncovering tumor- and blood-based molecular profiles that inform cancer heterogeneity, metastasis, and therapeutic resistance. Machine learning and AI-driven models further enhance these datasets by stratifying patient populations, predicting therapeutic responses, and expediting the discovery of actionable targets and companion biomarkers. This synergy between technology, automation, and high-dimensional data analytics enables individualized treatment strategies in melanoma, lung, and other cancer types. Aligned with international programs such as the Cancer Moonshot and the ICPC, the Lund Center's approach fosters open collaboration and data sharing on a global scale. This scalable, patient-centric biobanking paradigm provides an adaptable model for institutions aiming to unify clinical, molecular, and computational resources for transformative cancer research.
Quantitative Top-Down Proteomics Reveals Significant Differences in Histone Proteoforms Between Metastatic and Nonmetastatic Colorectal Cancer Cells.
Fang F, Fries B, Wang Z … +3 more , Liu X, Hummon AB, Sun L
Proteomics · 2025 Dec · PMID 40243858 · Full text
Colorectal cancer (CRC) development is closely associated with the accumulation of both genetic and epigenetic alterations. Many efforts have been made to investigate the role of epigenetic modifications in CRC metastasi...
Colorectal cancer (CRC) development is closely associated with the accumulation of both genetic and epigenetic alterations. Many efforts have been made to investigate the role of epigenetic modifications in CRC metastasis. In this work, we present the quantitative top-down proteomics study focusing on histone proteoforms between metastatic (SW620) and nonmetastatic (SW480) CRC cells to reveal potentially critical histone proteoforms in CRC metastasis. We isolated histone proteins from CRC cells, fractionated them by sodium dodecyl-sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), and analyzed them by capillary zone electrophoresis (CZE)-tandem mass spectrometry (MS/MS). A total of 230 histone proteoforms were quantified in SW480 and SW620 cell lines, among which 34 proteoforms were significantly altered in abundance in the metastatic cells, indicating a significant transformation of histone proteoforms during metastasis. We observed a significant increase in abundance of all nine differentially expressed histone H4 proteoforms in metastatic SW620 cells compared to SW480 cells, while differentially expressed proteoforms of other histone proteins display diversified expression patterns. Additionally, two histone H2A proteoforms with a combination of N-terminal acetylation and phosphorylation were upregulated in the metastatic CRC cells. These differentially expressed histone proteoforms could be novel proteoform biomarkers of CRC metastasis.
Recent implementations of data-independent acquisition for cancer biomarker discovery in biological fluids.
Ha A, Woolman M, Waas M … +2 more , Govindarajan M, Kislinger T
Expert Rev Proteomics · 2025 Apr · PMID 40227112 · Publisher ↗
INTRODUCTION: Cancer is the second-leading cause of death worldwide and accurate biomarkers for early detection and disease monitoring are needed to improve outcomes. Biological fluids, such as blood and urine, are ideal...
INTRODUCTION: Cancer is the second-leading cause of death worldwide and accurate biomarkers for early detection and disease monitoring are needed to improve outcomes. Biological fluids, such as blood and urine, are ideal samples for biomarker measurements as they can be routinely collected with relatively minimally invasive methods. However, proteomics analysis of fluids has been a challenge due to the high dynamic range of its protein content. Advances in data-independent acquisition (DIA) mass spectrometry-based proteomics can address some of the technical challenges in the analysis of biofluids, thus enabling the ability for mass spectrometry to propel large-scale biomarker discovery. AREAS COVERED: We reviewed principles of DIA and its recent applications in cancer biomarker discovery using biofluids. We summarized DIA proteomics studies using biological fluids in the context of cancer research over the past decade, and provided a comprehensive overview of the benefits and challenges of DIA-MS. EXPERT OPINION: Various studies showed the potential of DIA-MS in identifying putative cancer biomarkers in a high-throughput manner. However, the lack of proper study design and standardization of methods across platforms still needs to be addressed to fully utilize the benefits of DIA-MS to accelerate the biomarker discovery and verification processes.
Plasticity of Gene Expression in Spaceflight and Postflight in Relation to Cardiovascular Disease: Mechanisms and Candidate Repurposed Drugs.
Bourdakou MM, Loizidou EM, Spyrou GM
Proteomics · 2025 Jun · PMID 40223711 · Full text
Spaceflight poses unique challenges to human health due to exposure to increased levels of cosmic radiation, microgravity, and associated oxidative stress. These environmental factors can lead to cellular damage, inflamm...
Spaceflight poses unique challenges to human health due to exposure to increased levels of cosmic radiation, microgravity, and associated oxidative stress. These environmental factors can lead to cellular damage, inflammation, and a range of health complications, including cardiovascular problems, immune system impairment, and an increased risk of cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the body's defense mechanisms against oxidative stress by promoting the expression of antioxidant enzymes. Recent research has shed more light on the critical role of NRF2 in addressing space-related health challenges. In this study, we developed a computational methodology to explore the plasticity of the gene expression profile in flight and postflight conditions, highlighting the genes and corresponding mechanisms that do not return to ground levels and correlate with gene signatures associated with cardiovascular disease (CVD). RNA sequencing (RNA-seq) data from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used to investigate the cellular effects of microgravity on cardiac function. Gene expression monotonicity studies were performed and linked to genome-wide association studies (GWAS) to highlight the monotonically expressed genes associated with CVD. The selected monotonically expressed genes were also mapped onto the NRF2 network to investigate the impact of spaceflight on human cardiomyocyte function in the context of redox signaling pathways. Based on this knowledge, we used computational drug repurposing methods to suggest a short list of repurposed drug candidates that can be further tested in astronauts for the prevention of CVD. This study provides insights into the molecular and redox signaling alterations in cardiomyocytes induced by spaceflight, laying the foundation for future research aimed at mitigating cardiovascular risks in astronauts and advancing clinical applications on Earth.
Proteomic insights into the molecular mechanism of anlotinib inhibition in TP53-mutated non-small cell lung cancer.
Jiang JM, Cheng ZW, Zhang L … +5 more , Tan TF, Zhang T, Shi HB, Hou KF, Xia Q
J Proteomics · 2025 May · PMID 40113013 · Publisher ↗
OBJECTIVE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. The aim of this...
OBJECTIVE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. The aim of this study was to investigate the inhibitory effect of anlotinib on TP53-mutated NSCLC and its possible mechanism. METHODS: The growth ability of TP53-mutated NSCLC cells were tested by Cell counting kit-8 assay. Proteins in TP53-mutated NSCLC cells treated with anlotinib were analyzed using label-free liquid chromatography-mass spectrometry. Differentially represented proteins were analyzed by KEGG, GO, and PPIs. TP53 pathway related proteins were verified using western blotting. RESULTS: The cell viability was significantly reduced in TP53-mutated NSCLC cell as opposed to TP53 wild cell by anlotinib treatment. 126 differentially represented proteins (37 upregulated and 89 downregulated) were found between the anlotinib and control groups in TP53-mutated NSCLC cell. Bioinformatics analyses revealed that the differentially represented proteins were primarily involved in catalytic activity, cellular processes, and metabolite interconversion. PANTHER Classification System found that anlotinib mainly impacted the p53 signaling pathway, De novo purine biosynthesis and Integrin signaling. KEGG enrichment and PPI networks of the differentially represented proteins revealed cyclin-dependent kinase 1 (CDK1) and mitogen-activated protein kinase kinase 3 (MAP2K3) as the core protein, which are related to the p53 signaling pathway. Western blotting also revealed that anlotinib significantly suppressed the expression of CDK1 and MAP2K3 in TP53-mutated NSCLC cells, that indicated the possible mechanism may involve the MAP2K3/p53/CDK1 pathway. CONCLUSIONS: Our findings showed that anlotinib selectively inhibited the growth of TP53-mutated NSCLC cells and downregulated the expression levels of CDK1 and MAP2K3. The MAP2K3/p53/CDK1 pathway may be the molecular mechanism underlying anlotinib's efficacy in TP53-mutated NSCLC. STATEMENT OF SIGNIFICANCE: Tumor protein 53 (TP53) is the commonly mutated gene in non-small cell lung cancer (NSCLC) that is associated with poor prognosis, and anlotinib exerts inhibitory effects on TP53-mutated NSCLC. However, the action mechanism of anlotinib in the treatment of TP53-mutated NSCLC remains unclear. In this study, we used label-free quantitative proteomics to reveal the molecular mechanism of anlotinib inhibition in TP53-mutated NSCLC. We found that anlotinib significantly inhibited the growth of TP53-mutated NSCLC cells and downregulated the expression levels of CDK1 and MAP2K3. The MAP2K3/p53/CDK1 pathway may be the molecular mechanism underlying anlotinib's efficacy in TP53-mutated NSCLC. Our study promotes the use of anti-angiogenic drugs in TP53-mutated NSCLC. It provides new ideas for the treatment of TP53-mutated NSCLC.
Monitoring Functional Posttranslational Modifications Using a Data-Driven Proteome Informatic Pipeline.
Nickchi P, Vadadokhau U, Mirzaie M … +3 more , Baumann M, Saei AA, Jafari M
Proteomics · 2025 Apr · PMID 40100226 · Full text
Posttranslational modifications (PTMs) are of significant interest in molecular biomedicine due to their crucial role in signal transduction across various cellular and organismal processes. Characterizing PTMs, distingu...
Posttranslational modifications (PTMs) are of significant interest in molecular biomedicine due to their crucial role in signal transduction across various cellular and organismal processes. Characterizing PTMs, distinguishing between functional and inert modifications, quantifying their occupancies, and understanding PTM crosstalk are challenging tasks in any biosystem. Studying each PTM often requires a specific, labor-intensive experimental design. Here, we present a PTM-centric proteome informatic pipeline for predicting relevant PTMs in mass spectrometry-based proteomics data without prior information. Once predicted, these in silico identified PTMs can be incorporated into a refined database search and compared to measured data. As a practical application, we demonstrate how this pipeline can be used to study glycoproteomics in oral squamous cell carcinoma based on the proteome profile of primary tumors. Subsequently, we experimentally identified cellular proteins that are differentially expressed in cells treated with multikinase inhibitors dasatinib and staurosporine using mass spectrometry-based proteomics. Computational enrichment analysis was then employed to determine the potential PTMs of differentially expressed proteins induced by both drugs. Finally, we conducted an additional round of database search with the predicted PTMs. Our pipeline successfully analyzed the enriched PTMs, and detected proteins not identified in the initial search. Our findings support the effectiveness of PTM-centric searching of MS data in proteomics based on computational enrichment analysis, and we propose integrating this approach into future proteomics search engines.
On the Ocean of Biomarkers for the Precise Diagnosis and Prognosis of Lung Diseases.
Pham VD, Lee JH, Shin D … +5 more , Vu HM, Jung J, Kashyap MK, Lee SH, Kim MS
Proteomics Clin Appl · 2025 May · PMID 40098318 · Publisher ↗
Bronchoalveolar lavage fluid (BALF) has long been used for diagnosing various lung diseases through its cellular components. However, the clinical utility of biomolecules in the BALF remains largely unexplored. Recently,...
Bronchoalveolar lavage fluid (BALF) has long been used for diagnosing various lung diseases through its cellular components. However, the clinical utility of biomolecules in the BALF remains largely unexplored. Recently, mass spectrometry-based proteomics has been applied to profile the BALF proteomes to identify novel biomarkers for lung diseases. This review discusses the current progress in the field of BALF proteomics and highlights its potential as a valuable source of biomarkers for different lung diseases. Additionally, we explored the latest advancements and findings from BALF studies. Finally, we address the current limitations and propose future directions and research opportunities to advance the study of BALF.
Comparative proteomic profiling of glioblastoma and healthy brain cell-derived extracellular vesicles reveals enrichment of cancer-associated proteins.
Hutson HK, Qin G, Cai C … +1 more , Nestorova GG
J Proteomics · 2025 May · PMID 40058457 · Publisher ↗
Extracellular vesicles (EVs)-mediated cellular communication plays a role in cancer development and progression. This study focuses on identifying glioblastoma-specific EV protein markers through a comparative mass spect...
Extracellular vesicles (EVs)-mediated cellular communication plays a role in cancer development and progression. This study focuses on identifying glioblastoma-specific EV protein markers through a comparative mass spectrometry bottom-up proteomic analysis of the LN-229 cell line and human neurons, astrocytes, and endothelial brain cells (HEBCs) using timsTOF Pro 2 instrument. The statistically significant upregulated proteins with fold change greater than 2 in the glioblastoma-derived EVs were clustered based on physical and functional interactions using the STRING database and analyzed using Gene Ontology enrichment. LN229-derived EVs contained an average of 2635 proteins, while human astrocytes, neurons, and HEBC encapsulated 2647, 716, and 2285 proteins, respectively. NanoParticle Tracking Analysis indicated that glioblastoma-derived EVs exhibited greater size variability compared to EVs from healthy cells. Statistical analysis identified 25 statistically significant proteins with increased levels in LN229 EVs relative to at least two healthy cell lines suggesting their potential as glioblastoma markers. Functional clustering using the STRING database and GO analysis indicated involvement in epigenetic regulation, metastasis, angiogenesis, and protein folding. Post-translational modification analysis identified a subset of 17 proteins unique to the cancer-derived EVs involved in chromatin regulation, extracellular matrix remodeling, and basement membrane organization pathways, highlighting their role in tumor progression.
Monitoring Changes in the Levels of Newly Synthesized Proteins in Response to Nutlin-3 Treatment.
Way L, Hernychova L, Vialaret J … +4 more , Ruidong L, Vojtesek B, Hupp T, Mannaa AM
Proteomics · 2025 Apr · PMID 40051194 · Publisher ↗
Developing methodological approaches for discovering novel pathways is a key challenge in the life science research. Biological pathways are regulated-in higher eukaryotes-by a vast diversity of linear peptide motifs tha...
Developing methodological approaches for discovering novel pathways is a key challenge in the life science research. Biological pathways are regulated-in higher eukaryotes-by a vast diversity of linear peptide motifs that mediate combinatorial specificity in signal transduction pathways. The E3 ubiquitin ligase component (MDM2) is such a protein that interacts with target proteins containing linear motifs such as p53. Drug leads, such as Nutlin-3, that bind to the MDM2 hydrophobic pocket mimic p53 and can release p53 from MDM2 control and this can lead to cell death. However, these drug leads act allosterically, having agonist effects on MDM2's functions and there are other proteins whose steady state levels can be altered by Nutlin-3. As cell density can alter the proliferation state of cell populations, we examined the impact of Nutlin-3 on levels of newly synthesized proteins using pulse-SILAC mass spectrometry. The data demonstrate that at differing cell densities or population-wide proliferation rates, different newly synthesized proteins dominate the proteome landscape in a Nutlin-3 dependent manner. These data further confirm that the cell state in a population of cells can in turn impact on the MDM2 signalling landscape. This methodology forms a blueprint for biomarker discovery using clinical samples that can detect changes in the synthesis rate of proteins in cell populations treated with specific agents. Broader implications highlight tools that can be used to study allosteric regulation of protein-drug combinations.
Dynamic Proteomic and Acetylomic Profiling of Mechanically Induced Cancer Stemness in Breast Cancer Cells.
Han R, Wu Y, Yang Y … +4 more , Wang Q, Ding T, Zhang X, Yang J
Proteomics · 2025 Apr · PMID 39981796 · Publisher ↗
Compared to regular tumor cells, cancer stem cells exhibit dangerous characteristics, including high proliferation, high metastatic potential, and significantly increased in vivo tumorigenicity. Although some studies hav...
Compared to regular tumor cells, cancer stem cells exhibit dangerous characteristics, including high proliferation, high metastatic potential, and significantly increased in vivo tumorigenicity. Although some studies have emphasized the impact of the microenvironment on cell stemness, they have largely overlooked the mechanical forces derived from the stiffness of the surrounding extracellular matrix. Our previous research demonstrated that a 90 Pa soft fibrin matrix in three-dimensional (3D) culture can induce cells to become cancer repopulating cells with high stemness. Acetylation modification significantly influences the metabolism, epigenetics, proliferation, migration, and immune evasion of tumor cells. In this study, we performed a comprehensive analysis of the proteome and acetyl-proteome of breast cancer cells under two-dimensional (2D) plate and 3D matrix conditions with varying stiffness. This dataset provides a valuable resource for understanding the dynamic regulation of protein acetylation in response to mechanical stiffness. The mass spectrometry-based proteomics data have been uploaded to the ProteomeXchange Consortium with the dataset identifier PXD057820.
Salivary Proteome Is Altered in Children With Small Area Thermal Burns.
Carlton M, Zang T, Parker TJ … +3 more , Punyadeera C, Voisey J, Cuttle L
Proteomics Clin Appl · 2025 Mar · PMID 39895030 · Full text
Saliva is a child appropriate biofluid, but it has not previously been used to evaluate the systemic response to burn injury in children. The aim of this study was to investigate the salivary proteome of children with sm...
Saliva is a child appropriate biofluid, but it has not previously been used to evaluate the systemic response to burn injury in children. The aim of this study was to investigate the salivary proteome of children with small area thermal skin burns relative to different burn characteristics (mechanism, time to re-epithelialization and risk of emotional distress). SWATH Mass Spectrometry was used to quantify the abundance of 742 proteins in the saliva of children with burns (n = 22) and healthy controls (n = 37). Eight proteins were differentially abundant in the saliva of children with burns compared to healthy children, and these were associated with immune processes, epidermal cell differentiation and transferrin receptor binding. Eleven proteins were differentially abundant in patients with burns of different mechanisms. Scald burns had an over-representation of immune/inflammatory response processes, and contact burns had an over-representation of cornification, intermediate filament assembly and cell death cellular processes. Four proteins were elevated in patients who were at high risk for emotional distress and 15 proteins were correlated with time to wound re-epithelialization. This pilot study proves that saliva can be used for paediatric biomarker discovery and can be used as a diagnostic and prognostic sample to investigate systemic changes in a paediatric burn cohort.
The Contribution and Perspectives of Proteomics to Epithelial Ovarian Cancer.
Pei J, Qiu H, Wang W … +5 more , Wang Y, Wang M, Wang D, Li J, Qin Y
Proteomics Clin Appl · 2025 Mar · PMID 39865556 · Publisher ↗
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy which mainly consists of serous, mucinous, clear cell, and endometrioid subtypes. Due to the lack of classic symptoms at an early stage, EOC usual...
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy which mainly consists of serous, mucinous, clear cell, and endometrioid subtypes. Due to the lack of classic symptoms at an early stage, EOC usually presented as advanced tumors with local and/or distant metastasis. Although a large portion of EOC was initially platinum-sensitive, most patients would acquire resistance to common chemotherapeutic agents. These aforementioned issues lead to a challenge for clinical treatments and unsatisfying outcomes. Previous studies have demonstrated the genetic features of EOC are hard to target and the alterations at DNA and RNA levels are not fully represented at the protein expression profiles which made it more complex. In recent years, a panel of studies attempted to explore the key proteins involved in the development and progression of EOC using high-throughput proteomic technologies. We herein summarized them to provide a full view of this topic.
Oncoproteins E6/E7 of the human papillomavirus types 16 & 18 synergize in modulating oncogenes and tumor suppressor proteins in colorectal cancer.
Fernandes Q, Therachiyil L, Younis SM … +2 more , Dermime S, Al Moustafa AE
Expert Rev Proteomics · 2025 Feb · PMID 39815804 · Publisher ↗
OBJECTIVE: Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC). METHODS: HCT 116 (KRAS mutant) & HT-...
OBJECTIVE: Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC). METHODS: HCT 116 (KRAS mutant) & HT-29 (TP53 mutant) cell models of CRC were transduced with E6/E7 of HPV16 and HPV18, individually and in combination. Further, we utilized a liquid chromatography mass spectrometry (LC-MS/MS) approach to analyze and compare the proteomes of both CRC cell models. RESULTS: We generated six stably transduced cell lines. Our data revealed a significantly higher, HPV-induced modulation of oncogenes and tumor suppressor proteins in the TP53 mutant model, as compared to the KRAS mutant model ( ≤ 0.01). Less than 1% of the genes were commonly modulated by HPV, between both models. We also report that HT-29 cells, expressing E6/E7 of both HPV types, significantly reduced the suppression of oncogenes as compared to cells expressing E6/E7 of either HPV types individually (p-value ≤0.00001). CONCLUSION: Our data imply that HPV coinfections leads to the sustenance of a pro-oncogenic environment in CRC. HPV modulates different oncogenes/tumor suppressor proteins in CRC of varying mutational backgrounds, thus highlighting the importance of personalized therapies for such diseases with mutational heterogeneity.
Interaction and regulation of the mitochondrial proteome - in health and disease.
Palmfeldt J
Expert Rev Proteomics · 2025 Jan · PMID 39806765 · Publisher ↗
INTRODUCTION: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabol...
INTRODUCTION: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabolic disorders, complex and common disorders like neurodegeneration, diabetes, and cancer, since they all to some degree have mitochondrial underpinnings. AREAS COVERED: The main mitochondrial functions and pathways are outlined, and systematic protein lists are presented. The main energy metabolic pathways are as follows: iron-sulfur cluster synthesis, one carbon metabolism, catabolism of hydrogen sulfide, kynurenines and reactive oxygen species (ROS), and others, described with the aim of laying a foundation for systematic mitochondrial pathway analysis based on proteomics data. The links of the proteins and pathways to functional effects and diseases are discussed. The disease examples are focussed on inherited metabolic disorders, cancer, neurological, and cardiovascular disorders. EXPERT OPINION: To elucidate the role of mitochondria in health and disease, there is a need for comprehensive proteomics analyses with stringent, systematic data treatment for proper interpretation of mitochondrial pathway data. In that way, comprehensive hypothesis-based research can be performed based on proteomics data.
Identifying therapeutic strategies for triple-negative breast cancer via phosphoproteomics.
Sheng Y, Mills G, Zhao X
Expert Rev Proteomics · 2024 Nov · PMID 39588933 · Publisher ↗
INTRODUCTION: Given the poor prognosis of patients with TNBC, it is urgent to identify new biomarkers and therapeutic targets to enable personalized treatment strategies and improve patient survival. Comprehensive insigh...
INTRODUCTION: Given the poor prognosis of patients with TNBC, it is urgent to identify new biomarkers and therapeutic targets to enable personalized treatment strategies and improve patient survival. Comprehensive insights beyond genomic and transcriptomic analysis are crucial to improved outcomes for patients. As proteins are the workhorses of cellular function with their activity primarily regulated by phosphorylation, advanced phosphoproteomics techniques, such as mass spectrometry and antibody arrays, are essential for elucidating kinase signaling pathways that drive TNBC progression and contribute to therapy resistance. AREA COVERED: This review discusses the critical need to integrate phosphoproteomics into TNBC research, evaluates commonly used technologies and their applications, and explores their advantages and limitations. We highlight significant findings from phosphoproteomic analyses in TNBC and address the challenges of implementing these technologies into clinical practice. EXPERT OPINION: Rapid advances in phosphoproteomics analysis facilitate subtype stratification, adaptive response monitoring, and identification of biomarkers and therapeutic targets in TNBC. However, challenges in analyzing protein phosphorylation, especially in deep spatially resolved analysis of malignant cells and the tumor ecosystem, hinder the translation of phosphoproteomics to the CLIA setting. Nonetheless, phosphoproteomics offers a powerful tool that, when integrated into routine clinical practice, has the potential to revolutionize patient care.
Proteogenomic profiling of acute myeloid leukemia to identify therapeutic targets.
Murray HC, Sillar J, Chambers M … +1 more , Verrills NM
Expert Rev Proteomics · 2024 Nov · PMID 39576246 · Publisher ↗
INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive and poor-prognosis blood cancer. Despite a low mutation burden compared to other cancers, AML is heterogenous and identifying robust therapeutic targets has bee...
INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive and poor-prognosis blood cancer. Despite a low mutation burden compared to other cancers, AML is heterogenous and identifying robust therapeutic targets has been difficult. Genomic profiling has greatly advanced our understanding of AML, and has revealed targets for AML therapy. However, only 50% of AML patients have gene mutations that are currently druggable, and relapse rates remain high. The addition of proteomic profiling is emerging to address these challenges. AREAS COVERED: Using references collected through Pubmed, we review recent studies that have combined genomic and proteomic profiling (i.e. proteogenomic profiling), as well as studies that have additionally integrated other omics approaches, such as phosphoproteomics. We highlight how proteogenomic profiling promises to deconvolve the cellular pathways driving leukemogenesis, uncover novel therapeutic targets, and identify biomarkers of response to novel and existing therapies. EXPERT OPINION: Proteogenomic profiling is providing unparalleled insight into AML, and is beginning to identify robust biomarkers. Standardization of workflows will be required before mass spectrometry-based proteomic assays can be integrated into routine clinical use. However, the demonstrated ability to adapt signatures into biomarker panels that can be assayed by existing clinical workflows is enabling current clinical translation.
Advancements in Single-Cell Proteomics and Mass Spectrometry-Based Techniques for Unmasking Cellular Diversity in Triple Negative Breast Cancer.
Nalla LV, Kanukolanu A, Yeduvaka M … +1 more , Gajula SNR
Proteomics Clin Appl · 2025 Jan · PMID 39568435 · Full text
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer characterized by a lack of targeted treatment options. Intratumoral heterogeneity significantly drives disease progre...
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer characterized by a lack of targeted treatment options. Intratumoral heterogeneity significantly drives disease progression and complicates therapeutic responses, necessitating advanced analytical approaches to understand its underlying biology. This review aims to explore the advancements in single-cell proteomics and their application in uncovering cellular diversity in TNBC. It highlights innovations in sample preparation, mass spectrometry-based techniques, and the potential for integrating proteomics into multi-omics platforms. METHODS: The review discusses the combination of improved sample preparation methods and cutting-edge mass spectrometry techniques in single-cell proteomics. It emphasizes the challenges associated with protein analysis, such as the inability to amplify proteins akin to transcripts, and examines strategies to overcome these limitations. RESULTS: Single-cell proteomics provides a direct link to phenotype and cell behavior, complementing transcriptomic approaches and offering new insights into the mechanisms driving TNBC. The integration of advanced techniques has enabled deeper exploration of cellular heterogeneity and disease mechanisms. CONCLUSION: Despite the challenges, single-cell proteomics holds immense potential to evolve into a high-throughput and scalable multi-omics platform. Addressing existing hurdles will enable deeper biological insights, ultimately enhancing the diagnosis and treatment of TNBC.
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