Traditional biomarkers such as chromogranin A (CgA) and 5-HIAA remain important in neuroendocrine tumor (NET) care. However, recent research shows that inflammation within the tumor microenvironment plays a major role in NET progression, angiogenesis, and treatment response. As a result, inflammation-based biomarkers are gaining value in diagnosis and risk assessment.
Inflammation in NET Biology
NETs interact with stromal cells, fibroblasts, and immune cells that release cytokines including IL-6, IL-1β, TNF-α, IL-8, IL-18, and CRP. A 2022–2023 multi-cytokine study found these markers significantly elevated in gastroenteropancreatic NETs, with IL-6 correlating closely with tumor grade. These findings highlight how inflammatory pathways contribute to tumor growth and potential resistance to therapy.
Systemic Markers With Prognostic Value
A 2024 meta-analysis reported that CRP, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) correlate with overall and progression-free survival in NETs. Studies of peptide receptor radionuclide therapy (PRRT) also show that elevated CRP and NLR are associated with poorer treatment response.
Emerging Biomarkers to Consider
Key inflammation-related markers include IL-6, CRP, TNF-α, IL-1β, IL-8, IL-18, and NLR. Although nonspecific, these biomarkers can complement classical NET testing, improving risk stratification and monitoring during therapy.
Conclusion
As evidence continues to grow, integrating inflammatory biomarkers with established NET markers offers a more comprehensive and personalized approach to evaluating NET progression and treatment outcomes.
References
Pavel, R., et al. (2023). Inflammatory cytokines associated with diagnosis, tumor grade and prognosis in patients with neuroendocrine tumors. Cancers, 15(21), Article 5142. https://doi.org/10.3390/cancers15215142
Chen, Y., Liu, X., Zhao, L., & Wang, J. (2024). Prognostic value of inflammation-related biomarkers in patients with gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Journal of Clinical Oncology Research, 13(2), 115–128.
Di Mauro, M., et al. (2024). Role of systemic inflammatory factors in patients with gastroenteropancreatic neuroendocrine tumors treated with PRRT: A multicenter study. European Journal of Nuclear Medicine and Molecular Imaging, 51(4), 1180–1192.
Singh, R., Patel, M., & Lopez, A. (2024). Comparative analysis of chromogranin A and inflammatory cytokines in neuroendocrine tumors. Frontiers in Endocrinology, 15, Article 1348293. https://doi.org/10.3389/fendo.2024.1348293