Xin Dai1, Wenjing Pang2, Yufeng Zhou1, Weiyan Yao1, Lu Xia1, Cheng Wang3, Xi Chen3, Ke Zen3, Chen-Yu Zhang3, Yaozong Yuan1. 1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2. Department of Gastroenterology, Tianyou Hospital, Shanghai Tongji University School of Medicine, Shanghai, China. 3. Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Abstract
BACKGROUND: New-onset diabetes mellitus in pancreatic cancer has been recognized as a paraneoplastic phenomenon caused by the existence of the tumor. Circulating microRNAs (miRNAs) are emerging as non-invasive biomarkers for the detection of various cancers. In the present study, we hypothesized that a specific serum miRNA profile exists in pancreatic cancer-associated new-onset diabetes mellitus (PaC-DM). METHODS: Initial screening of differentially expressed miRNAs in pooled serum samples from 25 PaC-DM patients, 25 non-cancer new-onset type 2 diabetes mellitus (T2DM) patients, and 25 healthy controls was performed by TaqMan low-density arrays (TLDA). A stem-loop quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to confirm the relative concentrations of candidate miRNAs in 80 PaC-DM, 85 non-cancer new-onset T2DM patients, and 80 healthy controls. RESULTS: The TLDA identified 16 serum miRNAs that were significantly increased in PaC-DM samples. A combination of six serum miRNAs (miR-483-5p, miR-19a, miR-29a, miR-20a, miR-24, miR-25) was selected by qRT-PCR as a biomarker for PaC-DM. The area under the receiver operating characteristic curve (AUC) for the six-miRNA panel training and validation sets was 0.959 (95% confidence interval [CI] 0.890-1.028) and 0.902 (95% CI 0.844-0.955), respectively. The combination of these six miRNAs enabled the discrimination of PaC-DM from non-cancer new-onset T2DM with an AUC of 0.885 (95% CI 0.784-0.986) and 0.887 (95% CI 0.823-0.952) for the training and validation sets, respectively. CONCLUSION: The six-serum miRNA panel may have potential as a biomarker for the accurate diagnosis and discrimination of PaC-DM from healthy controls and non-cancer new-onset T2DM.
BACKGROUND: New-onset diabetes mellitus in pancreatic cancer has been recognized as a paraneoplastic phenomenon caused by the existence of the tumor. Circulating microRNAs (miRNAs) are emerging as non-invasive biomarkers for the detection of various cancers. In the present study, we hypothesized that a specific serum miRNA profile exists in pancreatic cancer-associated new-onset diabetes mellitus (PaC-DM). METHODS: Initial screening of differentially expressed miRNAs in pooled serum samples from 25 PaC-DM patients, 25 non-cancer new-onset type 2 diabetes mellitus (T2DM) patients, and 25 healthy controls was performed by TaqMan low-density arrays (TLDA). A stem-loop quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to confirm the relative concentrations of candidate miRNAs in 80 PaC-DM, 85 non-cancer new-onset T2DM patients, and 80 healthy controls. RESULTS: The TLDA identified 16 serum miRNAs that were significantly increased in PaC-DM samples. A combination of six serum miRNAs (miR-483-5p, miR-19a, miR-29a, miR-20a, miR-24, miR-25) was selected by qRT-PCR as a biomarker for PaC-DM. The area under the receiver operating characteristic curve (AUC) for the six-miRNA panel training and validation sets was 0.959 (95% confidence interval [CI] 0.890-1.028) and 0.902 (95% CI 0.844-0.955), respectively. The combination of these six miRNAs enabled the discrimination of PaC-DM from non-cancer new-onset T2DM with an AUC of 0.885 (95% CI 0.784-0.986) and 0.887 (95% CI 0.823-0.952) for the training and validation sets, respectively. CONCLUSION: The six-serum miRNA panel may have potential as a biomarker for the accurate diagnosis and discrimination of PaC-DM from healthy controls and non-cancer new-onset T2DM.