Blood, exosomes, FFPE (Formalin-Fixed Paraffin-Embedded) tissues, urine, and more are commonly used sample types in disease research. These samples are rich sources of biological information, offering significant resources for biomarker discovery, molecular subtyping, and disease mechanism studies. By comparing differences in protein composition across different populations and states, systematic disease research can be conducted, ultimately facilitating precision treatments.
Data-Independent Acquisition (DIA) proteomics technology is applicable to almost all sample types, enabling unbiased collection of all information within the samples. This technology provides superior solutions for achieving high coverage, accuracy, and in-depth analysis of protein composition. Below, let's explore case studies of DIA quantitative proteomics in various clinical sample types, aiming to assist clinical researchers in expanding their research horizons.
Case 1. Non-invasive proteomic biomarkers for the diagnosis of alcohol-related liver disease [1]
Alcohol-Related Liver Disease (ALD) is a leading cause of liver-related mortality worldwide, yet our understanding of its three key pathological features (fibrosis, inflammation, and steatosis) remains incomplete. This study established three sample cohorts: ALD patient screening cohort (GALA-ALD, n=459, including 79 tissue-plasma paired patients); healthy control cohort (GALA-HP, n=137); and ALD screening validation cohort (GALA-ALD, n=63). Using Data-Independent Acquisition (DIA) quantitative proteomics, plasma samples from 459 ALD patients and liver tissues from 79 individuals in the GALA-ALD cohort were subjected to proteomic analysis. Leveraging plasma proteomic data and machine learning, predictive models for early fibrosis (F2), inflammation (I2), and steatosis (S0) were constructed and subsequently validated in independent cohorts. Furthermore, the models' prognostic performance for liver-related events and all-cause mortality was confirmed by follow-up data. This study reaffirms previous findings and provides potential protein targets with diagnostic, prognostic, and therapeutic value in ALD, offering a reliable basis for clinical diagnosis and precision medicine.
Case 2. Complement and MAPK Activation Associated with Inflammatory Myocarditis in SARS-CoV-2
Inflammatory myocarditis is characterized by inflammation of the heart muscle accompanied by impaired cardiac function. Myocarditis, in a narrower sense, is commonly triggered by infectious agents like viruses, bacteria, mycoplasma, or fungi. Notably, patients infected with SARS-CoV-2 have been found to experience inflammatory myocarditis, although the precise molecular characteristics of this condition remain elusive. This study involved a cohort analysis of four groups of patients suspected of having myocarditis. These groups included one with 5 cases of SARS-CoV-2 infection, another with 4 cases of virus-related myocarditis, a third with 5 cases of immune-mediated myocarditis, and a fourth non-inflammatory control group. Employing 4D-DIA proteomics and transcriptomics techniques, the study analyzed FFPE samples from these diverse groups to investigate the biological pathways associated with cardiac inflammation in the context of SARS-CoV-2 infection.
Case 3. Proteomic Analysis Reveals that Fas Genetic Can Improve Platelet Function in Hemophilia
Apoptotic vesicles (apoVs) are nanovesicles derived from apoptotic cells and play crucial roles in various pathophysiological contexts. However, their detailed characteristics, specific surface markers, and biological properties have not been fully elucidated. DIA quantitative proteomic analysis was performed on apoVs and exosomes from three different sources: human bone marrow mesenchymal stem cells (hBMSCs), human adipose-derived mesenchymal stem cells (hASCs), and mouse bone marrow mesenchymal stem cells (mBMSCs). Validation was carried out using MRM proteomics combined with western blotting. Differences in functional protein cargo and surface markers between apoVs and exosomes were determined. Thirteen specific biomarkers enriched in apoVs were identified, and the effectiveness of apoVs in treating hemophilia mice was demonstrated through a previously unknown Fas/FasL chain mechanism.
References
- Niu, Lili, et al. "Noninvasive proteomic biomarkers for alcohol-related liver disease." Nature Medicine 28.6 (2022): 1277-1287.
- Weckbach, Ludwig T., et al. "Association of Complement and MAPK Activation With SARS-CoV-2–Associated Myocardial Inflammation." JAMA cardiology 7.3 (2022): 286-297.
- Zhang, Xiao, et al. "Proteomic analysis of MSC‐derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions." Journal of Extracellular Vesicles 11.7 (2022): e12240.
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