ZFHX3 methylation in peripheral blood monocytes as a potential biomarker for pancreatic cancer detection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers. OBJECTIVE: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC. METHODS: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel. RESULTS: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71). CONCLUSION: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.

Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms.

Background: CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4. Methods: This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis. Results: 100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively). Conclusion: Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.

Regulation of newly identified lysine lactylation in cancer.

Metabolic reprogramming is a typical hallmark of cancer. Enhanced glycolysis in tumor cells leads to the accumulation of lactate, which is traditionally considered metabolic waste. With the development of high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), the lactate-derived, lysine lactylation(Kla), has been identified. Kla can alter the spatial configuration of chromatin and regulate the expression of corresponding genes. Metabolic reprogramming and epigenetic remodeling have been extensively linked. Accumulating studies have subsequently expanded the framework on the key roles of this protein translational modification (PTM) in tumors and have provided a new concept of cancer-specific regulation by Kla.

Role of the intratumoral microbiome in tumor progression and therapeutics implications.

Microbes are widely present in various organs of the human body and play important roles in numerous physiological and pathological processes. Nevertheless, owing to multiple limiting factors, such as contamination and low biomass, the current understanding of the intratumoral microbiome is limited. The intratumoral microbiome exerts tumor-promoting or tumor-suppressive effects by engaging in metabolic reactions within the body, regulating signaling cancer-related pathways, and impacting both host cells function and immune system. It is important to emphasize that intratumoral microbes exhibit substantial heterogeneity in terms of composition and abundance across various tumor types, thereby potentially influencing diverse aspects of tumorigenesis, progression, and metastasis. These findings suggest that intratumoral microbiome have great potential as diagnostic and prognostic biomarkers. By manipulating the intratumoral microbes to employ cancer therapy, the efficacy of chemotherapy or immunotherapy can be enhanced while minimizing adverse effects. In this review, we comprehensively describe the composition and function of the intratumoral microbiome in various human solid tumors. Combining recent advancements in research, we discuss the origins, mechanisms, and prospects of the clinical applications of intratumoral microbiome.

FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1ß axis.

Obesity is an essential risk factor for pancreatic cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote cancer cell migration, invasion and metastasis under obese conditions. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages pyroptosis in a caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1ß axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1ß axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity.

Lipid metabolism reprogramming of CD8+ T cell and therapeutic implications in cancer.

Effector, memory and exhaustion are three phenotypes of CD8+ T cell. In tumor microenvironment (TME), metabolism dysfunction of the three should take the blame for immune escape. Against background of CD8+ T cell in normal development, multiple determinants in TME, including nutrition competition, PD-1 signals and other cancer - CD8+ T cell interactions, cause metabolism reprograming, including failure in energy metabolism and other abnormal lipid metabolism. Further, incompatibility among metabolism patterns of three phenotypes results in unresponsiveness of immune checkpoint blockade (ICB). Therefore, combination of ICB and drugs aiming at abnormal lipid metabolism provides promising direction to improve cancer therapy. This review focuses on lipid metabolism of CD8+ T cell and aims to provide innovative therapy strategy to cure cancer.

The characteristics of serum lipid spectrum in PanNENs and its correlation with clinicopathological features and prognosis.

Background: The role of dyslipidemia in pancreatic neuroendocrine tumors (PanNENs) is unclear. The aim of this study is to analyze the characteristics of serum lipid spectrum in PanNENs, and the effect of the variation in lipid profile on the development of PanNENs clinicopathological features and prognosis. Methods: All PanNENs patients between November 2012 and September 2020 in the authors' research center were identified from patient medical records and databases. A total of 185 with PanNENs patients were ultimately included in this study, including 100 nonfunctional PanNENs and 85 insulinomas. Clinicopathologic features, serum lipid level and overall survival results were retrospectively analyzed using statistical methods. Results: In 185 PanNENs, 95 (51.4%) patients appear to have dyslipidemia. Patients with insulinoma had a lower proportion of abnormal HDL than those with nonfunctional PanNENs (10.6% vs 23%, P=0.026). The mean serum HDL levels of insulinomas were 0.131 mmol/L higher than the NF-PanNENs (1.306 ± 0.324 vs 1.175 ± 0.315, P=0.006). In multivariate logistic analysis, high levels of HDL are negatively correlated to tumor size (OR 0.233, 95% CI: 0.069-0.790, P=0.019), but HDL was not associated with pathological grade or metastasis. And a correlation has been found between hypercholesterolemia and the original location of the tumor (OR:0.224, 95%CI: 0.066-0.753, P =0.016). In addition, the outcome of the survival analysis revealed that dyslipidemia did not influence the prognosis of PanNENs patients (P>0.05). Conclusions: HDL was negatively correlated with the tumor size of PanNENs. The serum HDL level of insulinoma patients is higher than nonfunctional PanNENs.

Fibrinogen-to-prealbumin ratio: A new prognostic marker of resectable pancreatic cancer.

Background: The fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of resectable pancreatic cancer has not been elucidated. Methods: A total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively. Results: The optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage. Conclusion: FPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions.

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms.

OBJECTIVES: High-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs. METHODS: Seventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan-Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses. RESULTS: Serum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs. CONCLUSIONS: Serum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.

Blood-based DNA methylation signatures in cancer: A systematic review.

DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.

Trade-offs between grain yields and ecological efficiencies in a wheat-maize cropping system using optimized tillage and fertilization management on the North China Plain.

Optimized fertilizer and tillage management can be an effective strategy for high ecological efficiencies as well as crop yields. The objective of this study was to assess the impact of diverse management practices on carbon footprint, and ecosystem services in a wheat-maize cropping system. An in situ field experiment field was conducted from 2018 to 2020 on the North China Plain, and six treatments were established: deep tillage (DT), shallow tillage (ST), no tillage (NT), deep tillage + adding organic fertilizer (DTF), shallow tillage + adding organic fertilizer (STF), and no tillage + adding organic fertilizer (NTF). The results showed that adding organic fertilizer and the deeper tillage depth caused higher direct CO2 and N2O emission fluxes. DTF treatment significantly increased carbon footprint either per-unit area (CFa) or per-unit net income (CFe). Compared with DT treatment, STF treatment had higher CFa but lower CFe by increasing net income through boosted crop yields. Besides, the highest ecosystem service values (ESV) were present in STF treatment during both 2 years (42,017.13 CNY ha-1 and 43,352.03 CNY ha-1). In conclusion, STF treatment was an optimal management practice to trade-off grain yields and ecological efficiencies in a wheat-maize cropping system. Furthermore, this study highlights that adding organic fertilizer could be an efficient option toward sustainable farmland utilization with high soil carbon sequestration capacity and high ESV.

Neoadjuvant therapy in pancreatic neuroendocrine neoplasms: A systematic review and meta-analysis.

Background and Objectives: Neoadjuvant therapy plays an increasingly important role in pancreatic neuroendocrine neoplasms (pNENs), but the systematic evaluation of its efficacy is still lacking. The purpose of this study is to explore the role of neoadjuvant therapy in pNENs. Methods: We systematically reviewed the literatures published online until October 1, 2021. Meta-analysis was conducted to generate proportion with 95% confidence intervals (95% CI) for tumor response, resection rate, R0 resection rate and survival time. Results: Nine studies with 468 patients were involved in the systematic review. None of these patients met complete response (CR). Furthermore, 43.6% (95% CI [18.1, 69.0]) patients were expected to achieve partial response (PR), 51.3% (95% CI [27.9, 78.3]) to stable disease (SD), and 4.3% (95% CI [0.7, 7.9]) to progressive disease (PD). The estimate resection rate and R0 resection rate after neoadjuvant therapy were 68.2% (95% CI [44.5, 91.9]) and 60.2% (95% CI [53.5, 66.9]), respectively. There was no significant difference in resection rate between different chemotherapy regimens (41.67% vs 33.93%, P=0.453), as well as R0 resection rate (62.50% vs 68.30%, P=0.605). In terms of objective response rate (ORR), there was no significant difference between CAPTEM and FAS (41.67% vs 33.93%, P=0.453), while PRRT showed a higher ORR compared with chemotherapy, although there was also no statistical difference (49.06% vs 36.96%, P=0.154). Conclusion: Neoadjuvant therapies could reduce the tumor size and stage of some borderline resectable or unresectable pNENs, and give some patients the chance of radical resection. However, according to the current data, the best treatment regimen for pNENs neoadjuvant therapy is still unknown.

COL17A1 facilitates tumor growth and predicts poor prognosis in pancreatic cancer.

OBJECTIVE: This study aimed to determine the role of COL17A1 in tumor progression and predict the prognosis of pancreatic cancer (PC). METHODS: RNA-seq data from The Cancer Genome Atlas and Genotype-Tissue Expression were analyzed using bioinformatics methods. "Limma" package was used to screen differentially expressed genes (DEGs). Prognostic-associated data were further analyzed using univariate Cox regression and verified using the GSE28375 and GSE62452 datasets. Protein-protein interaction (PPI) network analysis was integrated to screen for hub genes. In vitro quantitative real-time PCR (qPCR) and western blotting were used to detect gene expression. The functional attributes of PC cells were verified by wound healing assays, migration and invasion assays, Cell Counting Kit 8 (CCK8), and 5-ethynyl-2'-deoxyuridine (EdU) assay. RESULTS: On analyzing PC data, 4637 DEGs were identified. Of these, 2399 genes were upregulated and 2238 were downregulated. Through PPI network analysis, we identified that COL17A1 expression was highly correlated with poor prognosis of patients with PC. Functional attribute assays in the in vitro study showed that COL17A1 knockdown inhibited PC cell proliferation, migration, and invasion. CONCLUSIONS: According to our results, COL17A1 promotes PC cell proliferation, migration, and invasion mediated by the epithelial-mesenchymal transition (EMT) pathway. Thus, COL17A1 could be used as a prognostic marker in PC.

FABP4 in obesity-associated carcinogenesis: Novel insights into mechanisms and therapeutic implications.

The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors.

Gastroenteropancreatic neuroendocrine neoplasms G3: Novel insights and unmet needs.

According to the 2019 WHO pathology grading system, high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) can be divided into well differentiated neuroendocrine tumors G3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). GEP-NETs G3 and GEP-NECs present significant differences in driver genes and disease origin. NETs G3 and NECs have been confirmed to be two distinct diseases with different genetic backgrounds, however, this issue remains controversial. The prognosis of NETs G3 is significantly better than that of NECs. The differential diagnosis of GEP-NETs G3 and GEP-NECs should be combined with the patient's medical history, tumor histopathology, Ki-67 index, DAXX/ATRX, TP53 and Rb expression as well as other immunohistochemical indicators. In addition, the treatment strategies of these two subgroups are very different. Here, we summarize recent findings focused on the genomics, clinical manifestations, diagnosis, treatment and other aspects of high-grade GEP-NENs (G3). This review may help further our understanding of the carcinogenesis, diagnosis and treatment of GEP-NENs G3.

Exosomal linc-ROR mediates crosstalk between cancer cells and adipocytes to promote tumor growth in pancreatic cancer.

Exosomes are emerging as important mediators of the crosstalk between tumor cells and stromal cells in the microenvironment. However, the underlying molecular mechanism of pancreatic cancer (PC)-derived exosomes in the progression of the tumor microenvironment (TME) and crosstalk with adipocytes has not been elucidated. Exosomes isolated from PC cell culture supernatant through ultracentrifugation were rich in long intergenic non-coding ROR (linc-ROR). After constructing PC cell lines with stable linc-ROR knockdown or overexpression via the transfection of short hairpin RNA (shRNA) and pLent-U6-GFP-Puro, direct and indirect coculture systems were established to simulate the interaction between adipocytes and PC cells. Next, the effects of conditioned medium collected from dedifferentiated adipocytes on PC cell proliferation, motility, metastasis, and epithelial-mesenchymal transition (EMT) were evaluated by western blot analysis, colony forming, real-time cell analysis (RTCA), 5-ethynyl-2'-deoxyuridine (EdU), immunofluorescence (IF), Transwell, and wound-healing assays in vitro. Xenograft models were employed to identify whether conditioned medium loaded with interleukin-1ß (IL-1ß) promoted PC cell growth in vivo. Our results demonstrate that linc-ROR delivery via exosomes represents a brand-new perspective of dedifferentiating adipocytes in the TME of PC, which further induce PC cell EMT via the hypoxia inducible factor 1α (HIF1α)-ZEB1 axis. Moreover, exosomal linc-ROR may become a novel diagnostic marker for PC patients.

Fibrinogen/Albumin Ratio as a Promising Marker for Predicting Survival in Pancreatic Neuroendocrine Neoplasms.

BACKGROUND: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied. PATIENTS AND METHODS: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses. RESULTS: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR <0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006). CONCLUSION: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.

High pre-operative fasting blood glucose levels predict a poor prognosis in patients with pancreatic neuroendocrine tumour.

BACKGROUND: Hyperglycaemia has been indicated as a pro-tumoural factor; however, the prognostic role of diabetes mellitus (DM) in pancreatic neuroendocrine tumours (panNETs) remains ambiguous, partly due to the effects of anti-diabetic drugs. We hypothesise that the blood sugar level per se affects the outcome of panNETs, and thus, we investigated the prognostic significance of the fasting blood glucose (FBG) level in resected panNET patients with no pre-existing DM. METHODS: A retrospective cohort study comprising 201 patients with radically resected non-functional panNETs was conducted. A total of 164 patients without pre-existing DM were further studied. An FBG level greater than 5.6 mmol/L was defined as high (otherwise, normal). Survival was evaluated using Kaplan-Meier methods and log-rank tests. Multivariate analyses for survival were performed using the Cox regression model. RESULTS: High FBG levels were significantly associated with poor overall survival (OS; p = 0.019) and recurrence-free survival (RFS; p = 0.011) in resected patients with panNET who had no pre-existing DM. The multivariable-adjusted hazard ratios (HRs) for mortality and recurrence comparing patients with high and normal FBG levels were 12.19 (95% confidence interval (CI) = 1.15-128.78, p = 0.038) and 2.43 (95% CI = 1.03-5.72, p = 0.042), respectively. CONCLUSION: A pre-operative FBG level greater than 5.6 mmol/L is associated with poor OS and RFS metastasis for patients with panNET who undergo radical surgical resection.