## 6 Discussion  
The incidence of neuroendocrine tumors (NETs) has been steadily increasing in recent years [25]. Despite the fact that NETs develop slowly, in advanced cases, they are incurable and lead to death [26]. The diagnosis and therapy of neuroendocrine tumors (NETs) involve a variety of approaches due to their complexity and heterogeneity. Advanced imaging techniques, such as PET/CT with labeled somatostatin analogs, are crucial for accurately locating tumors and assessing their spread [27]. The treatment of NETs includes both surgical methods and pharmacological therapy, such as the use of somatostatin analogs and new targeted therapies like tyrosine kinase inhibitors, which show promising results in controlling tumor growth [28]. Additionally, radionuclide therapy with agents like 177 Lu-Dotatate offers an effective treatment option for patients with advanced NETs, significantly improving quality of life and extending survival [29]. Despite many years of research, treatment options are still limited. The three selected proteins were chosen for their roles in the Wnt signaling pathway, vital for regulating cell \begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Parameters**} & **BP-NET** & **GEP-NET** & \multirow{2}{*}{**z**} & \multirow{2}{*}{_p_} \\  & **Me (Q1–Q3)** & **Me (Q1–Q3)** & & \\ \hline
**IGF-1R [pg/mL]** & 27.2 (22.9–27.2) & 27.2 (19.7–27.2) & 0.04 & 0.968 \\ \hline
** ERK2 [pg/mL]** & 461.8 (378.0–560.5) & 430.4 (356.5–595.1) & 0.03 & 0.980 \\ \hline
**EGFR [pg/mL]** & 10,087 (9413–10,852) & 10,408 (9314–11,291) & 0.27 & \textless{}0.001 \\ \hline \hline \end{tabular} Legend: Me (Q1–Q3)—median (lower–upper quartile); z—Mann–Whitney U test statistic value, \(p\)—statistical significance.  
\end{table} 
Table 7: Concentrations of parameters related to BP-NETs and GEP-NETs. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Parameters**} & \multicolumn{3}{c}{**Study Group**} \\ \cline{2-4}  & & \(\rho\) & \(p\) \\ \hline \multirow{3}{*}{**Chromogranin A [\(\mu\)g/L]**} & IGF-1R & \(-\)0.041 & 0.722 \\  & ERK2 & 0.025 & 0.830 \\  & EGFR & 0.296 & \textless{}0.05 \\ \hline \multirow{3}{*}{**Serotonin [ng/mL]**} & IGF-1R & 0.067 & 0.568 \\  & ERK2 & \(-\)0.145 & 0.214 \\  & EGFR & 0.222 & 0.061 \\ \hline \multirow{3}{*}{**5-hydroxyindole acetic acid**} & IGF-1R & 0.092 & 0.422 \\  & ERK2 & 0.121 & 0.293 \\ \cline{1-1}  & EGFR & 0.150 & 0.200 \\ \hline \hline \end{tabular} Legend: \(\rho\)—[PERSON]’s correlation coefficient, \(p\)—statistical significance.  
\end{table} 
Table 8: Concentration of parameters related to known NET marker. metabolism, proliferation, differentiation, and apoptosis [23]. The focus on these proteins aims to offer a clearer understanding of the molecular mechanisms in neuroendocrine tumors. An interesting target for treatment is mTOR inhibitors in patients with NETs. Mutations in the mammalian target of rapamycin (mTOR) pathway are estimated to occur in approximately 14% of pancreatic NETs (pNEIs), and such abnormalities have also been associated with more aggressive tumors [30; 31; 32]. Clinical trials with everolimus, an oral mTOR inhibitor, in patients with NETs showed a significant improvement in progression-free survival after its use [33]. Studies show that IGF-1 is the main regulator of neuroendocrine secretion and growth [34; 35]. Moreover, in vitro studies have shown that IGF-1R blockade results in inhibition of NET cell growth and induction of apoptosis [36]. Other preclinical studies suggest that IGF-1 protects cancer cells from rapamycin-induced cell death and that inhibition of IGF-1R prevents rapamycin-induced Akt activation and sensitizes cancer cells to mTOR inhibitors, providing a rationale for the combined blockade of these pathways [37]. IGF-1R from rapamycin-induced apoptosis is independent of Ras-Erk1-Erk2 and phosphatidylinositol 3\({}^{\prime}\)-kinase-Akt signaling pathways [38].