Journal of Cancer Research
- ISSN: 2578-3726
Shota Gabadadze, Alexandre Tavartkiladze, Gaiane Simonia, Ruite Lou, Dinara Kasradze, Pati Revazishvili, Maia Maisuradze, Rusudan Khutsishvili, Revaz Turmanidze, Tatia Potskhoraia, Tamar Japaridze, Irine Andronikashvili, Pirdara Nozadze and Tamaz Mamukishvili
Metastatic non-small cell lung cancer (NSCLC), particularly adenocarcinoma, remains a leading cause of cancer mortality worldwide, with advanced stages presenting complex challenges in both management and treatment. The progression of NSCLC, especially when metastases are involved, is closely tied to systemic inflammation and alterations in the neuroendocrine system. This study aims to elucidate the septic processes associated with advanced NSCLC by examining the role of inflammatory markers, neurotransmitters, and tumor markers in patients with metastatic disease. We conducted a comparative analysis between two distinct patient groups: the first group included 41 patients with advanced NSCLC (adenocarcinoma, stage IV, G3-G4), all presenting multiple metastases in the liver, bones, brain, and adrenal glands, with detectable circulating tumor cells (CTCs) and cell-free DNA (ctDNA) in their blood. The second group, serving as a control, consisted of 41 patients with early-stage NSCLC (adenocarcinoma, stage I, G1-G3) who were free of CTCs and ctDNA in their blood. Inflammatory markers, including TNF-alpha, CRP, ferritin, IL-1beta, IL-6, serum amyloid A (SAA), erythrocyte sedimentation rate (ERS), and leukocytes, were measured in both groups. Our results revealed significant increases in all inflammatory markers in the advanced NSCLC group compared to the control group. Specifically, TNF-alpha levels were elevated by 70%, CRP by 20%, ferritin by 11%, IL-1beta by 29%, IL-6 by 49%, and SAA by 27%. The ERS was 19% higher, and the leukocyte count increased by 12.9%. These findings underscore the profound systemic inflammation associated with metastatic NSCLC, which likely contributes to the aggressiveness and metastatic potential of the disease.
In addition to inflammation, we assessed the levels of key neuromediators, including melatonin, dopamine, serotonin, adrenalin, noradrenalin, cortisol, and histamine, to explore the neuroendocrine alterations associated with cancer progression. Our analysis demonstrated a dramatic 90% reduction in both melatonin and dopamine levels in the advanced NSCLC group compared to the control group. In contrast, serotonin levels were increased by 11.2%, adrenalin by 2.5%, noradrenalin by 9.8%, cortisol by 21.7%, and histamine by 17.7%. The significant decrease in melatonin and dopamine, both of which play critical roles in immune regulation and anti-cancer defense, suggests that metastatic NSCLC patients may suffer from impaired immune responses and increased tumor growth. Furthermore, the elevations in serotonin, adrenalin, noradrenalin, cortisol, and histamine point to a hyperactive stress-response system in these patients, which may further exacerbate tumor progression through immune suppression and the promotion of a tumor-friendly microenvironment.
Tumor markers, including CYFRA, carcinoembryonic antigen (CEA), CTCs, and ctDNA, were also quantified in both groups. As expected, the advanced NSCLC group exhibited significant increases in all tumor markers. CYFRA levels were 19% higher, CEA increased by 29.5%, CTCs were elevated by 87.1%, and ctDNA was 84.3% higher compared to the control group. The substantial presence of CTCs and ctDNA in the blood of stage IV patients indicates a higher degree of tumor shedding and metastasis, which correlates with the heightened inflammatory and neuroendocrine changes observed.
In conclusion, this study provides compelling evidence that metastatic NSCLC (adenocarcinoma) is characterized by pronounced systemic inflammation, significant dysregulation of neurotransmitter levels, and elevated tumor markers. The interplay between these factors likely contributes to the aggressive nature of advanced NSCLC and its metastatic spread. Our findings suggest that targeting both inflammation and neuroendocrine pathways could offer novel therapeutic strategies for improving outcomes in patients with metastatic NSCLC. Future research should focus on exploring potential interventions aimed at reducing inflammation, restoring neurotransmitter balance, and inhibiting tumor marker activity to mitigate disease progression.