Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development

Duan, Xuejing; Wang, Weihao; Pan, Qi; Guo, Lixin

doi:10.3389/fonc.2021.730038

Cited by 21 publications

(20 citation statements)

References 113 publications

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“…The decreased levels of amino acids may imply the upregulation of the corresponding biosynthetic pathways in cancer (24). In addition, the relationship between diabetes mellitus (DM) and PDAC is complex (25), so the potential screening performance of isoleucine in high-risk individuals is also worth a mention. Suguru et al (26) have showed that the significantly increased level of isoleucine was associated with PDAC in DM.…”

Section: Discussionmentioning

confidence: 99%

Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma

et al. 2022

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Background & ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples.MethodsWe employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study.ResultsA total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC.ConclusionsThis study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.

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Section: Discussionmentioning

confidence: 99%

Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma

et al. 2022

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“…Variants of PDX1 and HNF1A genes are also linked with an increased risk of obesity, T2DM, or hyperglycemia [60][61][62]. Figure 2 summarizes the different mechanisms that are involved between T2DM and the development of PC [28].…”

Section: Genetic Mutations Driving Pancreatic Cancermentioning

confidence: 99%

“…Chronic inflammation, hyperglycemia, hyperinsulinemia, and abnormalities in insulin/insulin-like growth factor 1 (IGF-1) pathways are some of the proposed molecular mechanisms by which DM and PC are closely related, with emerging evidence showing a positive association between DM and the risk of PC [ 22 , 27 , 28 ].…”

Section: Reviewmentioning

confidence: 99%

“…NFкB and signal transducer and activator of transcription 3 (STAT3) pathways function closely and similarly as promoters of cell proliferation and inhibitors of programmed cell death [ 28 ]. In addition, TGF-B1 decreases the expression of E-cadherin (a tumor suppressor), which results in the induction of EMT.…”

Section: Reviewmentioning

confidence: 99%

“…Created using Google Slides by Sara Waqar[28].AGEs: advanced glycation end products; AMPK: adenosine monophosphate protein-activated kinase; IGF-1: insulin-like growth factor-1; LKB: liver kinase B; MAPK: mitogen-activated protein kinase; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor kappa B; PI3K: phosphatidyl inositol-3 kinase; STAT3: signal transducer and activator of transcription 3; TGF-β1: transforming growth factor-β1; TME: tumor microenvironment; PDX1: pancreatic and duodenal homeobox-1; HNF1A: hepatocyte nuclear factor-1 alpha; UCP2: uncoupling protein 2…”

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confidence: 99%

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The Role of Type 2 Diabetes in Pancreatic Cancer

George¹,

Jean-Baptiste²,

Ali³

et al. 2022

Cureus

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The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states.

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A prognostic model based on tumor microenvironment-related lncRNAs predicts therapy response in pancreatic cancer

Tan

2023

Funct Integr Genomics

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Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development

Cited by 21 publications

References 113 publications

Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma

Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma

The Role of Type 2 Diabetes in Pancreatic Cancer

A prognostic model based on tumor microenvironment-related lncRNAs predicts therapy response in pancreatic cancer

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