The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives
Abstract
1. Introduction
2. Methods
3. Protective Biological Functions of Omentin
3.1. Anti-Inflammatory and Immune Regulatory Roles
3.2. Antioxidant Effects and Oxidative Stress Modulation
3.3. Vascular Biology and Vascular Protective Functions
4. The Role of Omentin in Metabolic Disorders
4.1. Omentin and Obesity
4.2. Omentin, Insulin Resistance and Diabetes
4.3. Omentin and Metabolic Syndrome
4.4. Omentin and Metabolic–Associated Steatotic Liver Disease
5. The Role of Omentin in Gastrointestinal Cancers
5.1. Upper Gastrointestinal Cancer
5.1.1. Esophageal Cancer
5.1.2. Gastric Cancer
5.2. Hepato-Pancreato-Biliary (HPB) Cancer
5.2.1. Hepatocellular Cancer
5.2.2. Pancreatic Cancer
5.3. Colorectal Cancer
6. Directions and Research Needs
6.1. What Is Missing About Omentin’s Role in GI Cancers?
6.2. Clinical Utility
6.3. Proposals for Future Research Focusing on Translational and Clinical Studies
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Akt | Protein kinase B |
AMPK | AMP-activated protein kinase |
AUC | Area under the curve |
BE | Barrett’s esophagus |
CA19-9 | Carbohydrate antigen 19-9 |
CEA | Carcinoembryonic antigen |
CDX2 | Caudal-type homeobox 2 |
CP | Chronic pancreatitis |
CRC | Colorectal cancer |
CSC | Cancer stem cell |
CXCL2 | C-X-C motif chemokine ligand 2 |
EAC | Esophageal adenocarcinoma |
EPC | Endothelial progenitor cell |
ERK | Extracellular signal–regulated kinase |
ESCC | Esophageal squamous cell carcinoma |
HCC | Hepatocellular carcinoma |
HNF4α | Hepatocyte nuclear factor 4 alpha |
HOMA-IR | Homeostatic model assessment of insulin resistance |
HR | Hazard ratio |
IHC | Immunohistochemistry |
ITLN1 | Intelectin-1 (gene encoding omentin-1) |
JNK | c-Jun N-terminal kinase |
LF | Lactoferrin |
MAPK | Mitogen-activated protein kinase |
MASLD | Metabolic-associated steatotic liver disease |
MASH | Metabolic-associated steatohepatitis |
MDSC | Myeloid-derived suppressor cell |
miRNA | MicroRNA |
MSI | Microsatellite instability |
NF-κB | Nuclear factor kappa B |
NK cell | Natural killer cell |
Nrf2 | Nuclear factor erythroid 2–related factor 2 |
OR | Odds ratio |
PA | Pancreatic adenocarcinoma |
PDAC | Pancreatic ductal adenocarcinoma |
PI3K | Phosphoinositide 3-kinase |
PPAR-δ | Peroxisome proliferator-activated receptor delta |
qRT-PCR | Quantitative real-time polymerase chain reaction |
RFS | Recurrence-free survival |
ROC | Receiver operating characteristic |
ROS | Reactive oxygen species |
SIRT1 | Sirtuin 1 |
SNP | Single-nucleotide polymorphism |
TCGA | The Cancer Genome Atlas |
TMEM207 | Transmembrane protein 207 |
TNF-α | Tumor necrosis factor alpha |
TNM | Tumor–node–metastasis (staging) |
TOP/FOP | TCF reporter constructs for Wnt/β-catenin signaling |
VAT | Visceral adipose tissue |
VCAM-1 | Vascular cell adhesion molecule 1 |
VEGF | Vascular endothelial growth factor |
VLDL | Very low–density lipoprotein |
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Authors and Year | Cancer Type | Model | Findings | Role | Clinical Implication |
---|---|---|---|---|---|
Zhang et al., 2020 [59] | ESCC | ESCC (microarray + qRT-PCR) | ↑ ITLN1 linked to better OS/RFS; protective gene in 6-gene immune signature | Protective, prognostic | Favorable immune profile and improved survival |
Liang et al., 2021 [45] | ESCC | ESCC tumor and adjacent normal tissue | ↓ ITLN1 in tumors; associated with better immune contexture and lower immune risk score | Immune-modulating, prognostic | Immune biomarker; favorable prognosis |
Busslinger et al., 2021 [46] | EAC | Barrett’s esophagus and dysplasia/EAC tissue | ITLN1 expressed in BE epithelium; unchanged in progression to dysplasia or adenocarcinoma | Marker of metaplasia | Diagnostic utility in Barrett’s; no role in malignant transformation |
Zheng et al., 2012 [47] | Gastric | qPCR, IHC, survival analysis on tumors and normal tissue | ITLN1 mRNA 8× higher in tumors; associated with CDX2 expression, favorable histology, lower stage, improved survival (HR = 2.25 for ITLN1−) | Tumor suppressor downstream of CDX2 | Prognostic marker and therapeutic target for intestinal-type GC |
Li et al., 2023 [50] | hCC | 149 HCC patients (tissue analysis) | ↓ ITLN1 in 78% of tumors; associated with aggressive features and worse survival (HR ≈ 0.5) | Prognostic biomarker | Risk stratification tool post-resection |
Karabulut et al., 2016 [52] | Pancreatic | 33 PA patients vs. 30 controls (ELISA) | ↑ Omentin-1 (~9.6 vs. ~1.6 ng/mL); correlates with tumor size, not OS or chemo response | Diagnostic marker | Potential biomarker for detection, not for prognosis |
Kiczmer et al., 2018 [53] | Pancreatic | 25 PDAC, 10 CP, 36 controls (serum) | ↑ Omentin-1 in PDAC vs. controls; AUC 0.73; no correlation with TNM stage or BMI | Diagnostic adjunct | Support diagnosis; limited prognostic use |
Aleksandrova et al., 2016 [54] | CRC | Prospective cohort (n = 2295 subcohort + 251 CRC cases) | High baseline omentin-1 associated with increased CRC risk, especially in non-obese | Risk biomarker | Stratify risk, particularly in lean individuals |
Zhao et al., 2019 [55] | CRC | Case-control (358 CRC vs. 286 controls) | ↑ Omentin-1 in CRC; associated with advanced stage (pT3/4, TNM III–IV); AUC 0.88 | Diagnostic and staging marker | Non-invasive diagnostic tool with good sensitivity |
Feng et al., 2020 [56] | CRC | Prospective cohort (319 CRC vs. 300 controls) | Elevated pre-op omentin-1 predicts recurrence (HR 3.3) and mortality (HR 2.1) | Prognostic biomarker | Post-operative monitoring and treatment |
Uyeturk et al., 2014 [61] | CRC | Stage III post-FOLFOX patients (n = 45) | ↑ Omentin-1 after chemo; not correlated with metabolic parameters | Reactive or compensatory marker | Host response to therapy |
Zhang et al., 2021 [62] | CRC | Genetic association study (SNP) | Variant not associated with CRC overall; modifies risk in obesity | Gene–environment interaction | Stratify risk in obese patients based on genotype |
Fazeli et al., 2013 [63] | CRC | 39 CRC vs. 30 controls | ≈20× higher plasma omentin-1 in CRC; independent of BMI or stage | Carcinogenesis biomarker | Early detection |
Chen et al., 2021 [64] | CRC | TCGA + IHC (n = 229) | Low ITLN1 linked to worse OS; re-expression reduces EPCs and MDSCs | Microenvironment modulator | Therapeutic restoration enhances anti-tumor immunity |
Kim et al., 2012 [65] | CRC | Stage IV CRC proteomics | ITLN1 41× higher in long-term survivors; validated by WB/IHC | Prognostic biomarker | Survival indicator; guides treatment intensity |
Authors and Year | Cancer Type | Model | Findings | Role | Clinical Implication |
---|---|---|---|---|---|
Li et al., 2015 [49] | Gastric | In vitro (SGC-7901, AGS), in vivo (xenografts) | ITLN1 inhibits PI3K/NF-κB, restores HNF4α, suppresses β-catenin; reduces invasion/metastasis; positively correlates with OS (R = 0.82) | Tumor-suppressive adipokine | Dual biomarker with HNF4α; therapeutic target |
Zhang et al., 2013 [50] | HCC | HepG2, HuH-7 cell lines | Omentin-1 stabilizes p53 via SIRT1 inhibition; activates caspase-mediated apoptosis via JNK | Tumor suppressor | Potential therapeutic via p53 reactivation |
Cidem et al., 2024 [52] | HCC | HepG2, Hep3B, SK-Hep1 + orthotopic mice | LF requires omentin-1 for uptake; triggers apoptosis, cell-cycle arrest, inhibits angiogenesis | Therapeutic co-factor | Predictive biomarker and therapeutic enhancer for LF-based treatment |
Maeda et al., 2016 [58] | CRC | IHC + in vitro (siRNA) | TMEM207 loss reduces omentin secretion; correlates with nodal metastasis | Post-translational regulator | Potential target for therapy and prognosis |
Zhang et al., 2020 [60] | CRC | CRC tissue + SW480 cells | Tumors overexpress omentin-1; secreted in autocrine/paracrine fashion | Context-dependent role | Targeting tumor-derived omentin alters CRC progression |
Ji et al., 2019 [61] | CRC | CD133+ SW480 cells | Omentin-1 inhibits PI3K/Akt; reduces stemness and promotes apoptosis | Cancer stem cell suppressor | Adjuvant therapy targeting cancer stem cells |
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Mylonakis, A.; Frountzas, M.; Lidoriki, I.; Kozadinos, A.; Koloutsou, M.E.; Margoni, A.; Kalfoutzou, A.; Theodorou, D.; Toutouzas, K.G.; Schizas, D. The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives. Metabolites 2025, 15, 649. https://doi.org/10.3390/metabo15100649
Mylonakis A, Frountzas M, Lidoriki I, Kozadinos A, Koloutsou ME, Margoni A, Kalfoutzou A, Theodorou D, Toutouzas KG, Schizas D. The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives. Metabolites. 2025; 15(10):649. https://doi.org/10.3390/metabo15100649
Chicago/Turabian StyleMylonakis, Adam, Maximos Frountzas, Irene Lidoriki, Alexandros Kozadinos, Maria Evangelia Koloutsou, Angeliki Margoni, Areti Kalfoutzou, Dimitrios Theodorou, Konstantinos G. Toutouzas, and Dimitrios Schizas. 2025. "The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives" Metabolites 15, no. 10: 649. https://doi.org/10.3390/metabo15100649
APA StyleMylonakis, A., Frountzas, M., Lidoriki, I., Kozadinos, A., Koloutsou, M. E., Margoni, A., Kalfoutzou, A., Theodorou, D., Toutouzas, K. G., & Schizas, D. (2025). The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives. Metabolites, 15(10), 649. https://doi.org/10.3390/metabo15100649