A MicroRNA Signature Identifies Pancreatic Ductal Adenocarcinoma Patients at Risk for Lymph Node Metastases

Nishiwada, Satoshi; Sho, Masayuki; Banwait, Jasjit K.; Yamamura, Kensuke; Akahori, Toshikazu; Nakamura, Kota; Baba, Hideo; Goel, Ajay

doi:10.1053/j.gastro.2020.04.057

Cited by 38 publications

(22 citation statements)

References 71 publications

(81 reference statements)

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“…MiRNAs are small, noncoding RNAs consisting typically of 18–23 nucleotides, which can base-pair with complementary sequences in mRNA to silence RNA and post-transcriptionally regulate gene expression [ 23 ], such as during tumorigenesis and metastasis [ 24 ]. The molecular functions [ 25 , 26 ] and usefulness of these molecules as potential biomarkers [ 27 , 28 , 29 , 30 ] in pancreatic cancer have been reported, which suggests that new miRNA biomarkers for malignant IPMN could be found. However, one disadvantage of miRNAs as biomarkers is their lack of a definite internal control, which leads to inconsistent results across different studies.…”

Section: Introductionmentioning

confidence: 99%

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

Kuratomi

Takano

Fukasawa

et al. 2021

IJMS

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New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.

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Section: Introductionmentioning

confidence: 99%

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

Kuratomi

Takano

Fukasawa

et al. 2021

IJMS

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“…This indirect evaluation method limits the accuracy of its evaluation to a certain extent. Similarly, lncRNA (11) and miRNA (12) often have multi-target characteristics downstream that may perform different functions under different inflammation backgrounds and lack sufficient predictive stability. Recently, there has been a rise in the molecular subtype study of PDAC combining TME and transcriptome analysis, for example, basal-like and activated stromal subtype proposed by Moffitt et al (13) and pure basal-like and stromal activated subtypes identified by Puleo's group (14), which all suggest that the prognosis of patients is bad.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis

Yang

Zhou

et al. 2021

Front. Immunol.

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Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor characterized by rapid progression, early metastasis, high recurrence, and limited responsiveness to conventional therapies. The 5-year survival rate of PDAC is extremely low (<8%), which lacks effective prognostic evaluation indicators. In this study, we used xCell to analyze infiltrating immune cells in a tumor and through the univariate and multivariate Cox analyses screened out two prognosis-related immune cells, CD4+TN and common lymphoid progenitor (CLP), which were used to construct a Cox model and figure out the risk-score. It was found that the constructed model could greatly improve the sensitivity of prognostic evaluation, that the higher the risk-score, the worse the prognosis. In addition, the risk-score could also identify molecular subtypes with poor prognosis and immunotherapy sensitivity. Through transcriptome and whole-exome sequencing analysis of PDAC dataset from The Cancer Genome Atlas (TCGA), it was found that copy number deletion and low expression of CCL19 might be crucial factors to affect the risk-score. Lastly, validation of the above findings was confirmed not only in Gene Expression Omnibus (GEO) datasets but also in our PDAC patient samples, Peking2020 cohort.

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“…Additionally, LN metastasis is not correlated with this enlargement ( 23 ). A recent study reported that a six-microRNA risk prediction model could distinguish patients with PDAC patients exhibiting LN metastases from those with PDAC not exhibiting LN metastases (AUCof 0.84 and 0.73 in the training and validation sets, respectively) ( 24 ). In this study, the upregulated levels of Fuc-C4BPA were positively correlated with LN metastasis.…”

Section: Discussionmentioning

confidence: 99%

Fucosylated C4b‑binding protein α‑chain, a novel serum biomarker that predicts lymph node metastasis in pancreatic ductal adenocarcinoma

et al. 2020

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C4b-binding protein α-chain (C4BPA) was previously identified as a novel serum biomarker for pancreatic ductal adenocarcinoma (PDAC). To apply this biomarker for clinical diagnosis, a lectin ELISA was established to measure serum fucosylated (Fuc)-C4BPA levels in 45 patients with PDAC, 20 patients with chronic pancreatitis (CP) and 50 healthy volunteers (HVs) in one training and three validation sets. The lecithin ELISA developed in the current study exhibited satisfactory within-run (2.6–6.7%) and between-day (1.8–3.6%) coefficient of variations. Serum Fuc-C4BPA levels in patients with PDAC (0.54±0.27 AU/ml) was significantly higher than that in HVs (0.21±0.06 AU/ml; P<0.0001) and patients with CP (0.25±0.03 AU/ml; P<0.0001). Additionally, serum Fuc-C4BPA levels in preoperative patients were significantly decreased compared with postoperative patient sera (P<0.0003). The receiver operating characteristic (ROC) curve analyses revealed that the area under the curve (AUC) of Fuc-C4BPA (0.985) was higher than that of carbohydrate antigen (CA)19-9 (0.843), carcinoembryonic antigen (0.548) and total C4BPA (0.875) (P<0.001). To analyze the clinical significance of Fuc-C4BPA, the ability of Fuc-C4BPA to predict lymph node metastasis was compared with that of CA19-9. The AUC of serum Fuc-C4BPA levels (0.703) was significantly higher than that of serum CA19-9 levels (0.500) in patients with PDAC (P<0.001). The current study established a novel lectin ELISA for measuring serum Fuc-C4BPA levels. Thus, Fuc-C4BPA has potential clinical applications owing to its high diagnostic value in PDAC.

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A MicroRNA Signature Identifies Pancreatic Ductal Adenocarcinoma Patients at Risk for Lymph Node Metastases

Cited by 38 publications

References 71 publications

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis

Fucosylated C4b‑binding protein α‑chain, a novel serum biomarker that predicts lymph node metastasis in pancreatic ductal adenocarcinoma

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