ArticleJournal of experimental & clinical cancer research : CR2022
Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from "first contact" interactions in the tumor microenvironment.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- SFRP2 Potentiates Metastasis of Colon Cancer by Enhancing Snai1 Protein Stability via USP11.Journal of cellular and molecular medicine · 2026Article
- Crosstalk between immune and programmed cell death and their application in colorectal cancer risk stratification.Molecular and clinical oncology · 2026Article
- Profiling the pancreatic cancer secretome with metabolic glycoengineering.The Journal of biological chemistry · 2026Article
- KIF5B-driven unfolded protein response reprograms breast cancer immunosuppressive microenvironment for single-cell guided therapeutic targeting.Discover oncology · 2026Article
- RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement.Oncogene · 2026Article
- Secreted frizzled-related protein 2 monoclonal antibody-mediated IFN-ϒ reprograms tumor-associated macrophages to suppress triple negative breast cancer.Breast cancer research : BCR · 2025Article
- The pivotal role of SFRP2 in promoting glycolysis and progression in the high-risk group based on the glycometabolism prognostic model for colorectal cancer.Journal of gastroenterology · 2025Article
- Tumor Microenvironment: Recent Advances in Immunotherapies of Pancreatic Cancer.Medicina (Kaunas, Lithuania) · 2025Review
- Microfluidic Biochip-Based Multiplexed Profiling of Small Extracellular Vesicles Proteins Integrated with Machine Learning for Early Disease Diagnosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- The human microbiota: a double-edged sword against the 'Sword of Damocles' in PDAC diagnosis and therapy.Frontiers in oncology · 2025Review
- Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma.Current gene therapy · 2025Article
- Single cell analysis revealed SFRP2 cancer associated fibroblasts drive tumorigenesis in head and neck squamous cell carcinoma.NPJ precision oncology · 2024Article
- The role of kinesin family members in hepatobiliary carcinomas: from bench to bedside.Biomarker research · 2024Review
- Hands-Free Proteomic Profiling of Urinary Extracellular Vesicles with a High-Throughput Automated Workflow.Journal of the American Society for Mass Spectrometry · 2023Article
- Survival and Enrichment Analysis of Epithelial-Mesenchymal Transition Genes in Bladder Urothelial Carcinoma.Genes · 2023Article
- Functional and Clinical Proteomic Exploration of Pancreatic Cancer.Molecular & cellular proteomics : MCP · 2023Review
- Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson's disease.Communications medicine · 2023Article
- Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus.Diabetes research and clinical practice · 2023Article
- Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options.World journal of gastroenterology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPancreatic cancer is one of the most difficult cancers to detect early and most patients die from complications arising due to distant organ metastases. The lack of bona fide early biomarkers is one of the primary reasons for late diagnosis of pancreatic cancer. It is a multifactorial disease and warrants a novel approach to identify early biomarkers.
methodsIn order to characterize the proteome, Extracellular vesicles (EVs) isolated from different in vitro conditions mimicking tumor-microenvironment interactions between pancreatic cancer epithelial and stromal cells were analyzed using high throughput mass spectrometry. The biological activity of the secreted EVome was analyzed by investigating changes in distant organ metastases and associated early changes in the microbiome. Candidate biomarkers (KIF5B, SFRP2, LOXL2, and MMP3) were selected and validated on a mouse-human hybrid Tissue Microarray (TMA) that was specifically generated for this study. Additionally, a human TMA was used to analyze the expression of KIF5B and SFRP2 in progressive stages of pancreatic cancer.
resultsThe EVome of co-cultured epithelial and stromal cells is different from individual cells with distinct protein compositions. EVs secreted from stromal and cancer cells cultures could not induce significant changes in Pre-Metastatic Niche (PMN) modulation, which was assessed by changes in the distant organ metastases. However, they did induce significant changes in the early microbiome, as indicated by differences in α and β-diversities. KIF5B and SFRP2 show promise for early detection and investigation in progressive pancreatic cancer. These markers are expressed in all stages of pancreatic cancer such as low grade PanINs, advanced cancer, and in liver and soft tissue metastases.
conclusionsProteomic characterization of EVs derived from mimicking conditions of epithelial and stromal cells in the tumor-microenvironment resulted in the identification of several proteins, some for the first time in EVs. These secreted EVs cannot induce changes in distant organ metastases in in vivo models of EV education, but modulate changes in the early murine microbiome. Among all the proteins that were analyzed (MMP3, KIF5B, SFRP2, and LOXL2), KIF5B and SFRP2 show promise as bona fide early pancreatic cancer biomarkers expressed in progressive stages of pancreatic cancer.
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