Functional Genomics Approaches for the Identification of Tumor-Specific Biomarkers

Elena Ivanova^*
*Correspondence: Elena Ivanova, Department of Clinical Pathology, University of Belgrade, Serbia, Email:

Introduction

Inflammatory diseases, which encompass a wide range of conditions such as rheumatoid arthritis, Inflammatory Bowel Disease (IBD), and psoriasis, are characterized by chronic inflammation that can lead to significant tissue damage and long-term disability. The complexity of these diseases lies in their multifactorial nature, involving genetic, environmental, and immune system factors that contribute to disease onset and progression. Early diagnosis and effective prognosis prediction are critical for managing these conditions and minimizing damage. Traditionally, diagnosing and monitoring inflammatory diseases has relied on biomarkers such as C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR), but these markers are not always specific or sensitive enough to reflect disease severity or predict outcomes. In recent years, Extracellular Vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies, have emerged as promising biomarkers for the diagnosis and prognosis of inflammatory diseases. EVs are membrane-bound particles released by almost all cell types into the extracellular environment and contain a wide array of molecular cargo, including proteins, lipids, and nucleic acids. These characteristics make EVs valuable tools for understanding the pathogenesis of inflammation and for developing more accurate diagnostic and prognostic tools [1].

 

The potential of extracellular vesicles in inflammatory diseases lies in their ability to reflect the molecular changes occurring within the diseased tissues. EVs can carry bioactive molecules that mirror the status of the immune system, making them excellent candidates for monitoring disease activity and progression. They are involved in cell communication and have been shown to modulate immune responses by transferring inflammatory mediators between cells. For instance, in autoimmune diseases such as Rheumatoid Arthritis (RA), the release of EVs from inflamed synovial cells can carry pro-inflammatory cytokines, which are involved in amplifying the inflammatory response. Similarly, in conditions like Inflammatory Bowel Disease (IBD), EVs shed by immune cells in the gut mucosa can reflect changes in the inflammatory environment and contribute to the perpetuation of chronic inflammation. The ability of EVs to carry disease-specific molecular signatures, such as miRNAs, proteins, and lipid profiles, enables their use as biomarkers for both early diagnosis and predicting disease outcomes. Their presence in easily accessible body fluids, such as blood, saliva, or urine, further enhances their potential as a non-invasive diagnostic tool, revolutionizing the management of inflammatory diseases [2].

Description

Extracellular Vesicles (EVs) are classified into three major subtypes based on their size and biogenesis: exosomes, microvesicles, and apoptotic bodies. Exosomes, typically 30–150 nm in size, are secreted by most cell types and are involved in intercellular communication. They are formed within the endosomal network and released when the multivesicular bodies fuse with the plasma membrane. Exosomes contain a cargo of proteins, lipids, mRNA, and microRNAs, which can reflect the status of the cell from which they originate. In rheumatoid arthritis (RA), exosomes isolated from synovial fluid and blood have been shown to contain elevated levels of pro-inflammatory cytokines, matrix metalloproteinases, and other markers associated with joint inflammation. These EVs can also carry autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), which are key biomarkers for RA. By analyzing these vesicles, clinicians can gain valuable insights into the severity of inflammation, response to treatment, and disease progression. Furthermore, exosomes can also harbor microRNAs (miRNAs) that regulate gene expression and immune responses, offering an additional layer of diagnostic information. The ability of exosomes to carry specific inflammatory mediators, combined with their stability in circulation, positions them as promising biomarkers for non-invasive monitoring of RA and other autoimmune inflammatory diseases [3].

 

In Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and ulcerative colitis, EVs are being investigated as biomarkers for disease activity, diagnosis, and prognosis. Studies have shown that the levels of certain microRNAs and proteins in EVs correlate with the degree of inflammation in the intestinal mucosa. For example, exosomes derived from colonic epithelial cells in IBD patients have been found to carry miR-223, a microRNA involved in regulating immune responses and inflammation. Elevated levels of miR-223 in serum EVs are associated with active disease and could serve as an early indicator of flare-ups in IBD patients. Additionally, microvesicles isolated from the plasma of IBD patients often contain pro-inflammatory cytokines like TNF-α, which play a central role in the pathogenesis of the disease. By analyzing the cargo of these vesicles, clinicians can not only diagnose IBD more accurately but also predict future disease relapses or complications. The use of EVs for monitoring therapeutic responses is another promising application, as changes in EV composition over time may provide real-time information on how well a patient is responding to treatment, particularly in relation to biologic therapies such as anti-TNF agents or JAK inhibitors. This ability to track treatment efficacy with minimal invasiveness could lead to more personalized management strategies for IBD patients [4].

The role of extracellular vesicles extends beyond their diagnostic potential to their involvement in disease prognosis and therapeutic monitoring. In diseases like psoriasis, where inflammation leads to skin cell proliferation and the formation of plaques, EVs from lesional skin can carry specific biomarkers indicative of disease severity. Research has identified increased levels of certain cytokines in the EVs of psoriatic patients, including IL-17 and TNF-α, which are key drivers of the disease. Moreover, EVs can contain miRNAs that regulate T cell activation and inflammatory pathways, making them valuable for not only tracking disease activity but also understanding the underlying mechanisms. In addition, the presence of soluble proteins in EVs, such as C-Reactive Protein (CRP) and calprotectin, can provide insight into systemic inflammation and the likelihood of disease progression. The use of EVs to predict disease flares and remission could help guide the clinical decision-making process, reducing unnecessary treatments and improving patient outcomes. Furthermore, EVs can provide early biomarkers for detecting complications such as psoriatic arthritis, which can occur in some patients with psoriasis. As a result, the use of EVs in routine clinical practice holds the potential to not only enhance diagnostic accuracy but also provide valuable prognostic information for managing inflammatory diseases [5].

Conclusion

In conclusion, Extracellular Vesicles (EVs) represent a promising class of biomarkers for the diagnosis and prognosis of inflammatory diseases. Their ability to carry disease-specific molecular signatures, such as proteins, microRNAs, and lipids, makes them invaluable for monitoring disease activity, predicting outcomes, and assessing therapeutic responses. EVs provide a unique advantage in that they are stable in various body fluids, enabling non-invasive sampling and real-time monitoring of disease progression. In conditions such as Rheumatoid Arthritis (RA), Inflammatory Bowel Disease (IBD), and psoriasis, EVs can reflect the underlying inflammatory processes and provide insights into disease mechanisms long before clinical symptoms are evident. The integration of EV-based biomarkers into clinical practice offers the potential for earlier diagnosis, more personalized treatment plans, and better management of disease flares and complications. As research into EVs continues to evolve, their role in inflammatory disease diagnostics and prognostics will likely expand, offering clinicians new tools for improving patient care. With further validation and standardization of EV detection techniques, extracellular vesicles could become a cornerstone in the precision medicine approach to inflammatory diseases, offering an innovative and less invasive alternative to traditional biomarkers

References

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