Novel Blood Biomarkers of Pancreatic Cancer–Associated Diabetes Mellitus Identified by Peripheral Blood–Based Gene Expression Profiles

Huang, Hai; Dong, Xin; Kang, Mu Xing; Xu, Bin; Chen, Ying; Zhang, Bo; Chen, Jian; Xie, Qiu; Wu, Yu

doi:10.1038/ajg.2010.32

Cited by 83 publications

(56 citation statements)

References 36 publications

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“…Numerous genes were found to be differentially expressed on bioinformatic analysis of the gene expression profiles, consistent with former reports [16,17]. We then extracted secretory genes and did GO analysis.…”

Section: Discussionsupporting

confidence: 62%

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

Gao

Zhou

et al. 2015

Diabetologia

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Aims/hypothesis Pancreatic ductal adenocarcinoma (PDAC) can cause type 3C diabetes, known as PDAC-associated diabetes mellitus (PDAC-DM), but the mechanism is unknown. This study aimed to reveal the mechanism. Methods PDAC lesions from patients with or without PDAC-DM (n=4 in each group) were individually profiled for 23,512 mRNAs with microarrays. Bioinformatic analysis and in vivo and in vitro assays were then conducted. Results We determined that 2,778 genes were differentially expressed; over-representation of ten genes was validated with quantitative RT-PCR. The analysis of gene ontology showed that the differentially expressed secretory genes were related mainly to inflammation. High levels of a marker of inflammation (C-reactive protein [CRP]) and an inflammatory mediator (TNF super-family member 13 [TNFSF13]) were found in the serum of patients with PDAC-DM. After surgical resection of PDAC lesions, CRP and TNFSF13 levels significantly decreased (p<0.01). Furthermore, we found that the levels of TNFSF13 in PDAC lesions and TNFSF13 and CRP in serum were significantly correlated with the diabetic status of patients with PDAC-DM (p<0.01). Assays in vivo showed that after exposure to an inhibitor of inflammation (celecoxib), the fasting blood glucose level in the mouse model of PDACWenchao Gao, Yu Zhou and Qingyan Li contributed equally to this work Electronic supplementary material The online version of this article

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Section: Discussionsupporting

confidence: 62%

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

Gao

Zhou

et al. 2015

Diabetologia

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“…In addition, a recent study showed that the protein levels of renal vanin-1 increased in rats with streptozotocin-induced diabetic nephropathy, and urinary vanin-1 was detected in patients with diabetic nephropathy (Fugmann et al, 2011). Vanin-1 protein expression was detected in the pancreas of patients with pancreatic cancerassociated diabetes mellitus, but the Western blotting results for vanin-1 in serum were not available (Huang et al, 2010). Therefore, it is speculated that urinary vanin-1 might be of renal origin.…”

Section: Discussionmentioning

confidence: 99%

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

Hosohata

Ando²,

Fujimura³

2012

J Pharmacol Exp Ther

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Drug-induced nephrotoxicity is a serious problem in patients with hospital-acquired acute kidney injury (AKI). A new renal biomarker is needed because traditional markers are not sensitive for early detection of drug-induced AKI. In a recent study, we demonstrated that vanin-1 is a novel candidate biomarker of nephrotoxicant-induced kidney injury. The objective of the present study is to determine whether the increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-␤-glucosaminidase (NAG), kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL) in the two well established animal models of drug-induced AKI. After the administration of a higher dose of cisplatin (10 mg/kg, a single intraperitoneal dose) or gentamicin (120 mg/kg per day, once daily intraperitoneal dose for 9 days), urinary vanin-1 was detected earlier than the other biomarkers. In rats treated with a lower dose of cisplatin (5 mg/kg, a single intraperitoneal dose) or gentamicin (40 mg/kg per day, once daily intraperitoneal dose for 9 days), serum creatinine and urinary NAG were not changed throughout the study period, whereas urinary vanin-1, Kim-1, and NGAL were significantly increased. The renal vanin-1 protein levels were significantly decreased in rats treated with the higher dose of cisplatin on day 5 and gentamicin on day 9, and the immunofluorescence analyses confirmed that vanin-1 immunoreactivity in tubular cells was reduced with the time after the dose of cisplatin, indicating that urinary vanin-1 was leaked from tubular cells. These results suggest that, compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.

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“…Using microarray analysis, Pfeffer et al (2004) identified connexin 26, a gap junction protein, as being highly overexpressed in PC patients with DM. Using similar methods, Huang et al (2010) identified two upregulated genes in 27 patients with PC-associated DM, vanin-1 and matrix metalloproteinase 9, that Endocrine-Related Cancer (2012) 19 F9-F26 www.endocrinology-journals.org F17 together showed the best correlation with the diagnosis. No large-scale studies have been reported yet regarding the sensitivity and specificity of these possible biomarkers.…”

Section: Diabetes As a Consequence (And Harbinger) Of Pc The Prevalenmentioning

confidence: 99%

Diabetes and pancreatic cancer

Cui¹,

Andersen²

2012

Endocrine-Related Cancer

128

102

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Epidemiological studies clearly indicate that the risk of pancreatic cancer (PC) is increased in diabetic patients, but most studies focus on overall diabetes or type 2 diabetes mellitus (T2DM), and there are few studies on the risks of type 1 and type 3c (secondary) diabetes. Possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia, hyperinsulinemia, and abnormalities in insulin/IGF receptor pathways. Recently, insulin and insulin secretagogues have been observed to increase the PC risk, while metformin treatment reduces the cancer risk in diabetic subjects. In addition, anticancer drugs used to treat PC may either cause diabetes or worsen coexisting diabetes. T3cDM has emerged as a major subset of diabetes and may have the highest risk of pancreatic carcinoma especially in patients with chronic pancreatitis. T3cDM is also a consequence of PC in at least 30% of patients. Distinguishing T3cDM from the more prevalent T2DM among new-onset diabetic patients can be aided by an assessment of clinical features and confirmed by finding a deficiency in postprandial pancreatic polypeptide release. In conclusion, diabetes and PC have a complex relationship that requires more clinical attention. The risk of developing PC can be reduced by aggressive prevention and treatment of T2DM and obesity and the prompt diagnosis of T3cDM may allow detection of a tumor at a potentially curable stage.

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Novel Blood Biomarkers of Pancreatic Cancer–Associated Diabetes Mellitus Identified by Peripheral Blood–Based Gene Expression Profiles

Abstract: Our results indicate that the combination of VNN1 and MMP9 may be used as a novel blood biomarker panel for the discrimination of pancreatic cancer-associated diabetes from type 2 diabetes.

Cited by 83 publications

References 36 publications

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

Analysis of global gene expression profiles suggests a role of acute inflammation in type 3C diabetes mellitus caused by pancreatic ductal adenocarcinoma

Urinary Vanin-1 As a Novel Biomarker for Early Detection of Drug-Induced Acute Kidney Injury

Diabetes and pancreatic cancer

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