Pancreatic cancer is recognized as one of the most lethal types of cancer globally, characterized by a high mortality rate and a bleak prognosis, which greatly contributes to cancer-related deaths. Forecasts suggest that by 2030, pancreatic cancer will exceed other cancer types in prevalence. The disease presents considerable difficulties owing to the lack of prominent symptoms in its early stages, restricted options for early detection, rapid progression, and unfavorable outcomes. Presently, traditional methods for diagnosing pancreatic cancer primarily rely on imaging techniques. However, these methods often entail significant costs, require considerable time, and necessitate specialized skills for both operating the equipment and interpreting the resulting images. To overcome these obstacles, the use of biosensors has been proposed as a potentially valuable tool for the early detection of pancreatic cancer. MicroRNAs (miRs), a type of small non-coding RNA molecules, have emerged as highly sensitive molecular diagnostic tools that have the potential to function as precise indicators for a range of diseases, including cancer. Biosensors have been suggested as a potential solution for tackling these challenges, offering a promising approach for the early detection of pancreatic cancer. Small non-coding RNA molecules known as MicroRNAs (miRs) have become recognized as extremely sensitive molecular diagnostic tools and can act as precise biomarkers for different diseases, such as cancer. Moreover, this manuscript presents a thorough summary of the latest innovations in nano-biosensors that have been specifically developed for the identification of non-coding RNAs related to pancreatic cancer.

Biliary tract cancers are aggressive gastrointestinal malignancies characterized by a dismal 5-year overall survival rate <20%. Current diagnostic modalities suffer from limitations regarding sensitivity and specificity. This study aimed to develop a bile metabolite-based platform for precise discrimination between malignant and benign biliary diseases.

Samples were collected from 336 patients with biliary tract cancer or benign biliary diseases across 3 independent cohorts. Untargeted metabolic fingerprinting was performed on 300 bile samples using novel nanoparticle-enhanced laser desorption/ionization mass spectrometry. Subsequently, a diagnostic assay was developed based on the exploratory cohort using a selected bile metabolic biomarker panel, with performance evaluated in the validation cohort. Further external validation of disease-specific metabolites from bile samples was conducted in a prospective cohort (n = 36) using quantitative analysis. As a result, we established a novel bile-based assay, BileMet, for the rapid and precise detection of malignancies in the biliary tract system with an AUC of 0.891. We identified 6-metabolite biomarker candidates and discovered the critical role of the chenodeoxycholic acid glycine conjugate as a protective metabolite associated with biliary tract cancer.

Our findings confirmed the improved diagnostic capabilities of BileMet assay in a clinical setting. If applied, the BileMet assay enables intraoperative testing and fast medical decision-making for cases with suspected malignancy where brush cytology detection fails to support malignancy, ultimately reducing the economic burden by over 90%.

Liver cancer ranks as the sixth most common cancer globally, with hepatocellular carcinoma (HCC) accounting for approximately 75%-85% of cases. Most patients present with moderately advanced disease, while those with advanced HCC face limited and ineffective treatment options. Despite diagnostic efforts, no ideal tumor marker exists to date, highlighting the urgent clinical need for improved early detection of HCC. A key research objective is the development of assays that target specific pathways involved in HCC progression. This review explores the pathological origin and development of HCC, providing insights into the mechanistic rationale, clinical statistics, and the advantages and limitations of commonly used diagnostic tumor markers. Additionally, it discusses the potential of emerging biomarkers for early diagnosis and offers a brief overview of relevant assay methodologies. This review aims to summarize existing markers and investigate new ones, providing a basis for subsequent research.

It is still a challenging problem for clinicians to explore the nature of the indeterminate biliary strictures (IBSs). Approximately 20% of biliary strictures remain undetermined after a thorough preoperative assessment.

Here, we present two cases of indeterminate biliary strictures patients, whose cross- sectional imaging and endoscopic examination were nondiagnostic. The patients underwent exploratory laparotomy finally and were confirmed as malignancy. We also reviewed the recent reports in literatures regarding the evaluation of IBSs.

Given the majority of the biliary strictures are malignancy, preoperative differentiation between benign and malignant is critical for choosing the best therapeutic regimen. Thus, close follow-up, multiple multidisciplinary discussion, and prompt surgical exploration are necessary for some difficult diagnostic cases.

Routine measurement of cancer biomarkers is performed for early detection, risk classification, and treatment monitoring, among other applications, and has substantially contributed to better clinical outcomes for patients. However, there remains an unmet need for clinically validated assays of cancer protein biomarkers. Protein tumor markers are of particular interest since proteins carry out the majority of biological processes and thus dynamically reflect changes in cancer pathophysiology. Mass spectrometry-based targeted proteomics is a powerful tool for absolute peptide and protein quantification in biological matrices with numerous advantages that make it attractive for clinical applications in oncology. The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) based methodologies has allowed laboratories to overcome challenges associated with immunoassays that are more widely used for tumor marker measurements. Yet, clinical implementation of targeted proteomics methodologies has so far been limited to a few cancer markers. This is due to numerous challenges associated with paucity of robust validation studies of new biomarkers and the labor-intensive and operationally complex nature of LC-MS/MS workflows. The purpose of this review is to provide an overview of targeted proteomics applications in cancer, workflows used in targeted proteomics, and requirements for clinical validation and implementation of targeted proteomics assays. We will also discuss advantages and challenges of targeted MS-based proteomics assays for clinical cancer biomarker analysis and highlight some recent developments that will positively contribute to the implementation of this technique into clinical laboratories.

It is difficult to directly obtain pathological diagnosis of perihilar cholangiocarcinoma (pCCA). Analysis of bile in the pCCA microenvironment, based on metabolomics and statistical methods, can help in clinical diagnosis. Clinical information, bile samples, blood liver function, blood CA199, CEA, and other indicators were collected from 33 patients with pCCA and 16 patients with gallstones. Bile samples were analyzed using untargeted metabolomics methods. A combination of multivariate and univariate analyses were used to screen for potential differential metabolites Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and differential metabolite remodeling, we explored changes in the pCCA pathway and potential therapeutic targets. There were significant differences in patient blood TBIL, ALT, AST, TBA, CA19-9, and CEA indices (p < 0.05, |log2(fc)| ≥ 1) between two groups. A significant correlation was found between these different indicators by Spearman's analysis. The clinical parameters were correlated with mass-to-charge ratios of 305 (Positive Ion Mode, POS) and 246 (Negative Ion Mode, NEG) in the metabolic group (|r| ≥ 0.7, P ≤ 10^-7). The result of this study indicated that bile untargeted metabolomics combined with statistical analysis techniques may be used for diagnose and treatment of pCCA.

Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).

Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.