## 6 Discussion
The results of studies in patients with thyroid cancer show that the IGF-1-IGF-1R axis plays an important role in the development of PTC (papillary thyroid cancer) and ATC (anaplastic thyroid cancer) [39]. This suggests that serum concentrations of both cytokines can be considered additional markers of malignancy differentiation in the preoperative diagnosis of patients with thyroid cancer [40]. Moreover, IGF-1R values in serum seem to be a better predictor than IGF-1 concentrations [39; 41]. The two proteins differ in their sensitivity. For example, research indicates a strong association between elevated IGF-1R expression and increased resistance to radiation therapy in cancers such as cervical, prostate, lung, HPV-negative head and neck cancers, and melanoma [42; 43; 44; 45; 46]. Moreover, higher IGF-1R expression levels are linked to more aggressive tumor grades and reduced patient survival rates across various cancer types [47; 48; 49]. Our results show no statistically significant differences between the study and control groups for IGF-1R. There are no studies on the concentration of IGF-1R in patients with neuroendocrine tumors, nor are there studies on animal models. The only available research on IGF-1R concerns breast cancer patients [50; 51; 52; 53; 54; 55; 56]. The second analyzed protein, mitogen-activated protein (MAP) kinase ERK2 (p42), in association with ERK1 (p44), is a key component of the regulatory mechanism underlying cell proliferation [57]. The currently accepted model assumes that ERK1 and ERK2 are similarly regulated and contribute to intracellular signaling through phosphorylation [58]. Study results indicate an interplay between ERK1 and ERK2 in the transduction of Ras-dependent cell signaling and proliferation [59]. While ERK2 seems to play a positive role in controlling normal and Ras-dependent cell proliferation, ERK1 probably influences the overall cell signaling power by antagonizing ERK2 activity [60]. The molecular pathogenesis of gastrointestinal neuroendocrine tumors (GP-NETs) is unknown [61]. Serine/threonine kinase B-Raf has been identified as an oncogene in endocrine cancers such as thyroid cancer [62]. In endocrine cells, the small G protein Rap1 stimulates mitogen-activated protein kinase (MAPK) signaling by activating B-Raf [60]. The results of studies on the expression of Rap1 and B-Raf in GI NETs and their involvement in MAPK signaling in neuroendocrine cell lines indicate that Rap1-B-Raf signaling may contribute to the pathogenesis of GI NETs and provides a molecular target for GI NET treatment [63; 64]. There are no studies on the concentration of ERK2 in patients with neuroendocrine tumors, nor are there studies on animal models using immunoenzymatic methods. There are also no data for oncology patients. Our results show no statistically significant differences between the study and control groups for ERK2. This suggests that this protein may not be characteristic of neuroendocrine tumors, and therefore its potential as a predictor of this disease is low, or it should be analyzed using other molecular biology methods. Another molecule associated with the Akt signaling pathway is EGFR [65; 66; 67; 68; 69]. Although EGFR expression has been identified in neuroendocrine tumor tissue, its activation and the subsequent impact on downstream signaling molecules such as ERK1/2 and Akt remain unexplored. Further research is needed to elucidate these mechanisms and their potential implications for the behavior and treatment of neuroendocrine tumors [70]. Therefore, it was crucial to ascertain the role of EGFR in neuroendocrine tumors (NETs) by examining its expression and activation patterns, followed by the activation of additional signaling molecules [17; 25]. The study designed for this purpose included tumor tissue material from 98 patients with NETs. Immunohistochemistryichemical evaluation of EGFR, p-EGFR, p-Akt, and p-ERK1/2 expression was performed.