Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms
Abstract
:1. Introduction
2. Gastroenteropancreatic Neuroendocrine Tumors
3. Biochemical Diagnosis of GEP-NET
4. The Endocrine Role of Adipose Tissue and Inflammation in Obesity
5. Inflammation in Carcinogenesis
5.1. Interleukin 6
5.2. Tumor Necrosis Factor Alpha
5.3. Interleukin 17
5.4. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
5.5. Interleukin 10
5.6. Interleukin 12
5.7. Transforming Growth Factor β
6. Inflammatory Factors in GEP-NET
7. Obesity and Its Comorbidities and the Risk of GEP-NETs
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Type of Tumor | Characteristics of Subjects | Parameters | References |
---|---|---|---|
GEP-NET | 101 patients with GEP-NET and 150 controls (healthy volunteers); analysis of single nucleotide polymorphisms (SNPs) | IL-2-330 T/G, statistically significant association between high-expression GG genotype and high-expression G-allele and risk of GEP-NET | [139] |
GEP-NET | 101 patients with GEP-NET and 20 controls (healthy volunteers) | ↑IL-2 (highest in patients with functional GEP-NET); IL-2 more specific in detecting GEP-NET than CgA and 5-HIAA | [139] |
GEP-NEN | 43 patients with GEP-NENs | ↑TNF-α (correlation with tumor to higher grade and proliferation rates, expression positively correlated with death); ↑IL-6 with tumor grade (not statistically relevant); ↓IL-2, ↓IL-1β | [116] |
GEP-NET | 80 patients with GEP-NETs and 162 healthy controls; SNP IL-6-174 C/G and IL-6 serum values | ↑IL-6-174 CG/GG-NF-pNET (statistically significant with functional pNET); ↑IL-6 values serum: correlated significantly GG IL-6-174 genotype in all GEP-NETs, significantly higher IL-6 in NF-pNET with functional-pNET and GI-NET | [117] |
pNET | 60 patients with pNET and 60 healthy controls; IL-1β SNP (IL-1β-511-C/T, +3954C/T) and IL-1β serum values | High expression IL-1β-511-C/T in functional pNET (statistically significant); −511/+3954 CTCT: risk of developing functional pNET (statistically significant); −511/+3954 CTCC: risk of developing NF-pNET (statistically significant); IL-1β serum levels: undetectable | [121] |
GEP-NET | Human NET cell lines: BON (functional pNET, LCC-18 (NF-colorectal NET), QGP (NF-pNET), and cell lines BxPc3 and PANC-1 (human pancreatic carcinoma) | Expression TGF-β1 and its receptor TGF-βRI and TGF-βRII in three tested NET cell lines and in 67% of human NETs (possible inhibition of paracrine and autocrine growth by TGFβ1) | [126] |
GEP-NET | 38 patients with NENs and 23 healthy controls | ↑VEGF vs controls (statistically significant, also a significant increase with tumor progression); ↑angiogenin vs controls (statistically significant); ↑IL-8 vs control (statistically significant); highest level IL-6 in patients which non-survivors compared to survivors | [130] |
pNET | 52 cases of pancreatic adenocarcinoma and 52 with pNETs | IL-8, IL-8RA; IL-8RB expression in pNET (21%, 63%, 92%): no statistically significant correlation between the expression IL-8, IL-8RA; IL-8RB and tumor grade | [131] |
GEP-NET | 145 patients with GEP-NETs and 150 healthy controls | ↑VEGF in GEP-NETs vs healthy controls (the main with metastatic tumors; statistically significant); ↑VEGF in patients with metastases compared to patients with non-metastatic tumor (statistically significant); VEGF-1145G allele more frequent in NF-GI-NET than in controls (not statistically significant); Higher sensitivity VEGF than 5-HIAA but lower than CgA in tumor detection (both pNET and GI-NET); higher VEGF expression in midgut tumors than in foregut tumors (statistically significant difference) | [132] |
GEP-NET | 58 patients with GEP-NETs; the analysis of SNPs VEGFA, VEGFR2, and VEGFR3 | VEGF-A rs699947C, VEGF-A rs2010963GC, and VEGFR-3 rs307821C correlated with an increased risk of disease recurrence; | [133] |
NET | 115 patients with NETs | A correlation between NLR cut-off value above 3.01 and tumor localization (the main in the lung), higher histological grade, high mitosis, a high Ki-67 proliferation index, distant metastasis, and lymphovascular invasion; no correlations in the case of PLR. | [134] |
pNET | 172 patients with pNETs undergoing potentially curative resection (166 patients, curative resection and 6 patients, palliative surgery) | ↑NLR and ↑PLR significantly associated with shorter overall survival and disease-free survival. | [140] |
pNET | 165 patients with pNET | A correlation statistically significant between NLR cut-off value >2.4 with tumor size, tumor-node metastasis (stage III and IV), and tumor grade; no correlation NLR with age, gender, location, vessel, and nerve invasion. | [135] |
pNETs | 95 patients with resectable pNETs | ↑NLR is related with advanced tumor stage and higher grade (higher levels NLR in neuroendocrine carcinoma G3 than NET G1 and G2, higher in later stage, tumor thrombus and lymph node metastasis: statistically significant results; NLR independent risk factors for lymph node metastasis (significant differences between groups with and without lymph node metastasis) | [136] |
GEP-NET | 48 patients with GEP-NETs (foregut, midgut, and hindgut) that underwent resective surgery (curative GI-NET) | NLR >2.6 predicted the presence of peritoneal metastasis (statistically significant); PLR and PWR tended to predict the presence of multifocal disease but statistically insignificant | [137] |
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Budek, M.; Nuszkiewicz, J.; Piórkowska, A.; Czuczejko, J.; Szewczyk-Golec, K. Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms. Biomedicines 2022, 10, 2660. https://doi.org/10.3390/biomedicines10102660
Budek M, Nuszkiewicz J, Piórkowska A, Czuczejko J, Szewczyk-Golec K. Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms. Biomedicines. 2022; 10(10):2660. https://doi.org/10.3390/biomedicines10102660
Chicago/Turabian StyleBudek, Marlena, Jarosław Nuszkiewicz, Anna Piórkowska, Jolanta Czuczejko, and Karolina Szewczyk-Golec. 2022. "Inflammation Related to Obesity in the Etiopathogenesis of Gastroenteropancreatic Neuroendocrine Neoplasms" Biomedicines 10, no. 10: 2660. https://doi.org/10.3390/biomedicines10102660