Extracellular Vesicle Analysis Allows for Identification of Invasive IPMN

Yang, Katherine S.; Ciprani, Debora; O’Shea, Aileen; Liss, Andrew S.; Yang, Robert; Fletcher-Mercaldo, Sarah; Mino‐Kenudson, Mari; Castillo, Carlos Fernández‐del; Weissleder, Ralph

doi:10.1053/j.gastro.2020.11.046

Cited by 73 publications

(59 citation statements)

References 67 publications

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“…Cut-off value of cyst diameter is set at 4.0 cm in European guideline [ 8 ], but it is set as 3.0 cm in Fukuoka guideline [ 6 ].The follow-up management is also different among guidelines. In addition, a few studies have reported the use of an extracellular vesicle as a novel approach to predict malignant IPMNs [ 9 ]. However, few biomarkers have been reported to identify malignancy in BD-IPMNs.…”

Section: Introductionmentioning

confidence: 99%

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study

et al. 2021

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Background Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. Materials and methods 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. Results The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58–163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16–268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs. Conclusions HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.

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Section: Introductionmentioning

confidence: 99%

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study

et al. 2021

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“…It can be detected (mRNA expression) in the pancreatic tumor aspiration fluid (along with MUC1) of high-grade PanIN and PDA [ 40 ]. In IPMN management, MUC5AC detection in the extracellular vesicles can be a reliable biomarker to predict invasiveness and determine the need for surgery, as demonstrated by Yang et al [ 41 ]. Among the IPMN patients, MUC5AC in the extracellular vesicles help in identifying invasive IPMN from low-grade IMPN with a sensitivity of 82%, specificity of 100%, and a diagnostic accuracy of 96%.…”

Section: Pda and Muc5ac Expressionmentioning

confidence: 99%

Understanding the Clinical Impact of MUC5AC Expression on Pancreatic Ductal Adenocarcinoma

Manne

Esnakula

Abushahin

et al. 2021

Cancers

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Mucin-5AC (MUC5AC) is a heavily glycosylated gel-forming secreted mucin with a reliable prognostic value when detected in multiple malignancies. It is highly prevalent (70%) in PDA and is nonexistent in normal pancreatic tissues. Retrospective studies on PDA tumor tissue (detected by immunohistochemistry or IHC)) have investigated the prognostic value of MUC5AC expression but were equivocal. Some studies associated it with poor outcomes (survival or pathological features such as lymph node disease, vascular/neural invasion in resected tumors), while others have concluded that it is a good prognostic marker. The examination of expression level threshold (5%, 10%, or 25%) and the detected region (apical vs. cytoplasmic) were variable among the studies. The maturation stage and glycoform of MUC5AC detected also differed with the Monoclonal antibody (Mab) employed for IHC. CLH2 detects less mature/less glycosylated versions while 45M1 or 21-1 detect mature/more glycosylated forms. Interestingly, aberrantly glycosylated variants of MUC5AC were detected using lectin assays (Wheat Germ Agglutinin-MUC5AC), and Mabs such as NPC-1C and PAM4 have are more specific to malignant pancreatic tissues. NPC-1C and PAM4 antibody reactive epitopes on MUC5AC are immunogenic and could represent specific changes on the native MUC5AC glycoprotein linked to carcinogenesis. It was never studied to predict treatment response.

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“…Biotinylated detection antibodies combined with a tyramide signal amplification step, which catalyzes the addition of biotin groups from tyramide-biotin radicals near HRP, provide improved lower limits of detection [ 52 ]. The sensitivity of the approach is 10 4 -fold increased compared to traditional ELISA, which enables the detection of ultra-rare EVs and low abundance proteins [ 53 ].…”

Section: Clinical Applications Of Evs For Diagnosis Prognosis and Therapymentioning

confidence: 99%

Extracellular Vesicles in Lung Cancer: Prospects for Diagnostic and Therapeutic Applications

Kato

Vykoukal

Fahrmann

et al. 2021

Cancers

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Extracellular vesicles (EVs) are nano-sized lipid-bound particles containing proteins, nucleic acids and metabolites released by cells. They have been identified in body fluids including blood, saliva, sputum and pleural effusions. In tumors, EVs derived from cancer and immune cells mediate intercellular communication and exchange, and can affect immunomodulatory functions. In the context of lung cancer, emerging evidence implicates EV involvement during various stages of tumor development and progression, including angiogenesis, epithelial to mesenchymal transformation, immune system suppression, metastasis and drug resistance. Additionally, tumor-derived EVs (TDEs) have potential as a liquid biopsy source and as a means of therapeutic targeting, and there is considerable interest in developing clinical applications for EVs in these contexts. In this review, we consider the biogenesis, components, biological functions and isolation methods of EVs, and the implications for their clinical utility for diagnostic and therapeutic applications in lung cancer.

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Extracellular Vesicle Analysis Allows for Identification of Invasive IPMN

Cited by 73 publications

References 67 publications

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study

Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study

Understanding the Clinical Impact of MUC5AC Expression on Pancreatic Ductal Adenocarcinoma

Extracellular Vesicles in Lung Cancer: Prospects for Diagnostic and Therapeutic Applications

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