scholarly journals Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexander Ney ◽  
Andres Garcia-Sampedro ◽  
George Goodchild ◽  
Pilar Acedo ◽  
Giuseppe Fusai ◽  
...  

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Pattaya Seeree ◽  
Phorutai Pearngam ◽  
Supeecha Kumkate ◽  
Tavan Janvilisri

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy arising from the epithelial bile duct. The lack of early diagnostic biomarkers as well as therapeutic measures results in severe outcomes and poor prognosis. Thus, effective early diagnostic, prognostic, and therapeutic biomarkers are required to improve the prognosis and prolong survival rates in CCA patients. Recent advancement in omics technologies combined with the integrative experimental and clinical validations has provided an insight into the underlying mechanism of CCA initiation and progression as well as clues towards novel biomarkers. This work highlights the discovery and validation of molecular markers in CCA identified through omics approaches. The possible roles of these molecules in various cellular pathways, which render CCA carcinogenesis and progression, will also be discussed. This paper can serve as a reference point for further investigations to yield deeper understanding in the complex feature of this disease, potentially leading to better approaches for diagnosis, prognosis, and therapeutics.


2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.


2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.


Author(s):  
Narges Zafari ◽  
Azam Manshadi Tarafdari ◽  
Pantea Izadi ◽  
Mehrdad Noruzinia ◽  
Mir Saead Yekaninejad ◽  
...  

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlo De Matteis ◽  
Marica Cariello ◽  
Giusi Graziano ◽  
Stefano Battaglia ◽  
Patrizia Suppressa ◽  
...  

AbstractVisceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.


Zygote ◽  
2019 ◽  
Vol 27 (05) ◽  
pp. 263-271 ◽  
Author(s):  
Maryam Kiani ◽  
Mohammad Salehi ◽  
Asghar Mogheiseh

SummaryInfertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alien Balian ◽  
Frank J. Hernandez

AbstractEarly cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.


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