Quantitative assessment of the diagnostic role of mucin family members in pancreatic cancer: a meta-analysis.
Wang Shunda,You Lei,Dai Menghua,Zhao Yupei
Annals of translational medicine
Background:The use of mucins (MUC) as specific biomarkers for various malignancies has recently emerged. MUC1, MUC4, MUC5AC, and MUC16 can be detected at different stages of pancreatic cancer (PC), and can be valuable for indicating the initiation and progression of this disease. However, the diagnostic significance of the mucin family in patients with PC remains disputed. Herein, we assessed the diagnostic accuracy of mucins in PC using a meta-analysis. Methods:We searched the PubMed, Cochrane Library, Institute for Scientific Information (ISI) Web of Science, Embase, and Chinese databases from their date of inception to June 1, 2020 to identify studies assessing the diagnostic performance of mucins in PC. The estimations of diagnostic indicators in selected studies were extracted for further analysis by Meta-DiSc software. Publication bias was assessed using Deeks' funnel plot asymmetry test. Results:Our meta-analysis included 34 studies. The pooled accuracy indicators of MUC1 in PC including the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) (with 95% confidence intervals) were 0.84 (0.82-0.86), 0.60 (0.56-0.64), 18.37 (9.18-36.78), 2.62 (1.79-3.86), and 0.22 (0.15-0.33), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.8875 and the Q index was 0.8181. Quantitative random-effects meta-analysis of MUC4 in PC using the summary (ROC) curve model revealed a pooled sensitivity of 0.86 (95% confidence interval, 0.82-0.89) and specificity of 0.88 (95% confidence interval, 0.85-0.91). In addition, the meta-analysis of MUC5AC in PC diagnosis also showed a high sensitivity and specificity of 0.71 (95% confidence interval, 0.65-0.76) and 0.60 (95% confidence interval, 0.53-0.66), respectively. Regarding MUC16, the area under the summary ROC curve and Q index were 0.9185 and 0.8516, respectively. Conclusions:In summary, our results suggested a good diagnostic accuracy of several crucial mucins in PC. Mucins may serve as optional indicators in PC examination, and further research is warranted to investigate the role of mucins as potential clinical biomarkers.
10.21037/atm-20-5606
MUC Glycoproteins: Potential Biomarkers and Molecular Targets for Cancer Therapy.
Ratan Chameli,Cicily K D Dalia,Nair Bhagyalakshmi,Nath Lekshmi R
Current cancer drug targets
MUC proteins have great significance as prognostic and diagnostic markers as well as a potential target for therapeutic interventions in most cancers of glandular epithelial origin. These are high molecular weight glycosylated proteins located in the epithelial lining of several tissues and ducts. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Glycosylation, a post-translational modification affects the biophysical, functional and biochemical properties and provides structural complexity for these proteins. Aberrant expression and glycosylation of mucins contribute to tumour survival and proliferation in many cancers, which in turn activates numerous signalling pathways such as NF-kB, ERα, HIF, MAPK, p53, c-Src, Wnt and JAK-STAT, etc. This subsequently induces cancer cell growth, proliferation and metastasis. The present review mainly demonstrates the functional aspects of MUC glycoproteins along with its unique signalling mechanism and role of aberrant glycosylation in cancer progression and therapeutics. The importance of MUC proteins and its subtypes in a wide spectrum of cancers including but not limited to breast cancer, colorectal cancer, endometrial and cervical cancer, lung cancer, primary liver cancer, pancreatic cancer, prostate cancer and ovarian cancer has been exemplified with significance in targeting the same. Several patents associated with the MUC proteins in the field of cancer therapy are also emphasized in the current review.
10.2174/1568009620666201116113334
CA19-9 and CEA biosensors in pancreatic cancer.
Clinica chimica acta; international journal of clinical chemistry
Cancer is a complex pathophysiological condition causing millions of deaths each year. Early diagnosis is essential especially for pancreatic cancer. Existing diagnostic tools rely on circulating biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA). Unfortunately, these markers are nonspecific and may be increased in a variety of disorders. Accordingly, diagnosis of pancreatic cancer generally involves more invasive approaches such as biopsy as well as imaging studies. Recent advances in biosensor technology have allowed the development of precise diagnostic tools having enhanced analytical sensitivity and specificity. Herein we examine these advances in the detection of cancer in general and in pancreatic cancer specifically. Furthermore, we highlight novel technologies in the measurement of CA19-9 and CEA and explore their future application in the early detection of pancreatic cancer.
10.1016/j.cca.2024.117788
A review on recent advances in assays for DNMT1: a promising diagnostic biomarker for multiple human cancers.
The Analyst
The abnormal expression of human DNA methyltransferases (DNMTs) is closely related with the occurrence and development of a wide range of human cancers. DNA (cytosine-5)-methyltransferase-1 (DNMT1) is the most abundant human DNA methyltransferase and is mainly responsible for genomic DNA methylation patterns. Abnormal expression of DNMT1 has been found in many kinds of tumors, and DNMT1 has become a valuable target for the diagnosis and drug therapy of diseases. Nowadays, DNMT1 has been found to be involved in multiple cancers such as pancreatic cancer, breast cancer, bladder cancer, lung cancer, gastric cancer and other cancers. In order to achieve early diagnosis and for scientific research, various analytical methods have been developed for qualitative or quantitative detection of low-abundance DNMT1 in biological samples and human tumor cells. Herein, we provide a brief explication of the research progress of DNMT1 involved in various cancer types. In addition, this review focuses on the types, principles, and applications of DNMT1 detection methods, and discusses the challenges and potential future directions of DNMT1 detection.
10.1039/d3an01915b
Metabolomics identified new biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis.
Luo Xialin,Liu Jingjing,Wang Huaizhi,Lu Haitao
Pharmacological research
Pancreatic cancer (PC) is one of the most aggressive malignancies with high mortality due to a complex and latent pathogenesis leading to the severe lack of early diagnosis methods. To improve clinical diagnosis and enhance therapeutic outcome, we employed the newly developed precision-targeted metabolomics method to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can sensitively and efficiently diagnose the onsite progression of the disease. Many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer (n = 60) from healthy controls (n = 60). To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance. We eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); moreover, this plasma panel biomarker used for PC diagnosis is also quite convenient to implement in clinical practice. Using the same metabolomics method, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages. Taken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficient therapeutic interventions, which could largely improve the five-year survival rate of PC patients by significantly lowering clinical mortality.
10.1016/j.phrs.2020.104805
MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications.
Translational oncology
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance, apoptosis, autophagy, cell differentiation, tumor suppression, tumor growth, cancer cell proliferation, migration, and invasion in PC. Moreover, several aberrantly expressed miRNAs and lncRNAs have the potential to be used as biomarkers for accurate PC diagnosis. Additionally, miRNAs and lncRNAs are considered as promising clinical targets for PC. Therefore, in this review, we discuss recent experimental evidence regarding the clinical implications of miRNAs and lncRNAs in the pathophysiology of PC, their future potential, as well as the challenges that have arisen in this field of study in order to drive forward the design of ncRNA-based diagnostics and therapeutics for PC.
10.1016/j.tranon.2022.101579
Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer.
Cancer science
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.
10.1111/cas.16104
Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment.
Rong Zeyin,Xu Jin,Shi Si,Tan Zhen,Meng Qingcai,Hua Jie,Liu Jiang,Zhang Bo,Wang Wei,Yu Xianjun,Liang Chen
Theranostics
Pancreatic cancer (PC), an important cause of cancer-related deaths worldwide, is one of the most malignant cancers characterized by a dismal prognosis. Circular RNAs (circRNAs), a class of endogenous ncRNAs with unique covalently closed loops, have attracted great attention in regard to various diseases, especially cancers. Compelling studies have suggested that circRNAs are aberrantly expressed in different cancer tissues and cell types, including PC. More specifically, circRNAs can modify the proliferation, progression, tumorigenesis and chemosensitivity of PC, and some circRNAs could serve as biomarkers for diagnosis and prognosis. Herein, we summarize what is currently known to be related to the biogenesis, functions and potential roles of human circRNAs in PC and their application prospects for PC clinical treatments.
10.7150/thno.56174
Exosomes as Pleiotropic Players in Pancreatic Cancer.
De Lellis Laura,Florio Rosalba,Di Bella Maria Cristina,Brocco Davide,Guidotti Francesca,Tinari Nicola,Grassadonia Antonino,Lattanzio Rossano,Cama Alessandro,Veschi Serena
Biomedicines
Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response to current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis is of paramount importance for rational diagnostic and therapeutic approaches. Multiple lines of evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos of bioactive molecules to recipient cells within the tumor microenvironment and systemically. Intriguingly, exosomes may exert both protumor and antitumor effects, supporting or hampering processes that play a role in the pathogenesis and progression of PC, including shifts in tumor metabolism, proliferation, invasion, metastasis, and chemoresistance. They also have a dual role in PC immunomodulation, exerting immunosuppressive or immune enhancement effects through several mechanisms. PC-derived exosomes also induce systemic metabolic alterations, leading to the onset of diabetes and weight loss. Moreover, exosomes have been described as promising diagnostic and prognostic biomarkers for PC. Their potential application in PC therapy as drug carriers and therapeutic targets is under investigation. In this review, we provide an overview of the multiple roles played by exosomes in PC biology through their specific cargo biomolecules and of their potential exploitation in early diagnosis and treatment of PC.
10.3390/biomedicines9030275
Current status of molecular diagnostic approaches using liquid biopsy.
Journal of gastroenterology
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity.
10.1007/s00535-023-02024-4
A faecal microbiota signature with high specificity for pancreatic cancer.
Gut
BACKGROUND:Recent evidence suggests a role for the microbiome in pancreatic ductal adenocarcinoma (PDAC) aetiology and progression. OBJECTIVE:To explore the faecal and salivary microbiota as potential diagnostic biomarkers. METHODS:We applied shotgun metagenomic and 16S rRNA amplicon sequencing to samples from a Spanish case-control study (n=136), including 57 cases, 50 controls, and 29 patients with chronic pancreatitis in the discovery phase, and from a German case-control study (n=76), in the validation phase. RESULTS:Faecal metagenomic classifiers performed much better than saliva-based classifiers and identified patients with PDAC with an accuracy of up to 0.84 area under the receiver operating characteristic curve (AUROC) based on a set of 27 microbial species, with consistent accuracy across early and late disease stages. Performance further improved to up to 0.94 AUROC when we combined our microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19-9, the only current non-invasive, Food and Drug Administration approved, low specificity PDAC diagnostic biomarker. Furthermore, a microbiota-based classification model confined to PDAC-enriched species was highly disease-specific when validated against 25 publicly available metagenomic study populations for various health conditions (n=5792). Both microbiome-based models had a high prediction accuracy on a German validation population (n=76). Several faecal PDAC marker species were detectable in pancreatic tumour and non-tumour tissue using 16S rRNA sequencing and fluorescence in situ hybridisation. CONCLUSION:Taken together, our results indicate that non-invasive, robust and specific faecal microbiota-based screening for the early detection of PDAC is feasible.
10.1136/gutjnl-2021-324755
Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer.
Seminars in cancer biology
Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.
10.1016/j.semcancer.2023.11.003
Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter.
Biochimica et biophysica acta. Reviews on cancer
Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.
10.1016/j.bbcan.2020.188409
Correlation Between Baseline Serum Tumor Markers and Clinical Characteristic Factors in Patients with Advanced Pancreatic Cancer.
OncoTargets and therapy
PURPOSE:In pancreatic cancer (PC), CA 19-9, CEA and CA 125 are the most widely used tumor markers. The aim of this study was to explore the prognostic significance of baseline levels of serum CA 19-9, CEA, and CA 125, and to evaluate the clinical significance of these markers in PC patients. PATIENTS AND METHODS:A total of 278 patients with advanced PC that had received first-line chemotherapy treatments were examined. Correlation analysis between the tumor markers and clinical characteristics was performed using a Pearson's Chi-squared test or Fisher's exact test. A Pearson's correlation test was utilized to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated using a Kaplan-Meier analysis and compared using a Log rank test. Multivariate analysis was performed using a Cox proportional hazards regression model. RESULTS:Both individually and collectively, the baseline CA 19-9, CEA and CA 125 levels were positively associated with the primary tumor site ( < 0.01), liver metastasis ( < 0.05), and number of organ metastases ( < 0.05). Furthermore, CA 19-9, CEA and CA 125 were correlated to baseline WBC ( < 0.001) and LDH ( < 0.01) levels. Additionally, CA 19-9 was correlated with years of smoking ( = 0.024); diabetes and years of diabetes ( = 0.012); baseline glycemic levels ( = 0.004); and neutrophil counts ( < 0.001). Moreover, CA 125 levels were associated with the baseline neutrophil counts ( < 0.001) and peritoneal metastasis ( = 0.008). When examining neutrophil, LDH, CA 19-9 and CA 125 levels were found to be associated with overall survival (OS) and shown to be independent prognostic factors. CONCLUSION:CA 19-9, CEA and CA 125 are correlated with multiple clinical factors. Baseline neutrophil, LDH, CA 19-9 and CA 125 levels are associated with OS and may potentially serve as prognostic factors.
10.2147/OTT.S269720
Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS:Levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) in blood are used as markers to determine the response of patients with cancer to therapy, but are not used to identify patients with pancreatic cancer. METHODS:We obtained blood samples from 504 patients undergoing pancreatic surveillance from 2002 through 2018 who did not develop pancreatic cancer and measured levels of the tumor markers CA19-9, CEA, CA-125, and thrombospondin-2. Single-nucleotide polymorphisms (SNPs) in FUT3, FUT2, ABO, and GAL3ST2 that have been associated with levels of tumor markers were used to establish SNP-defined ranges for each tumor marker. We also tested the association between additional SNPs (in FUT6, MUC16, B3GNT3, FAM3B, and THBS2) with levels of tumor markers. To calculate the diagnostic specificity of each SNP-defined range, we assigned the patients under surveillance into training and validation sets. After determining the SNP-defined ranges, we determined the sensitivity of SNP-adjusted tests for the tumor markers, measuring levels in blood samples from 245 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) from 2010 through 2017. RESULTS:A level of CA19-9 that identified patients with PDAC with 99% specificity had 52.7% sensitivity. When we set the cut-off levels of CA19-9 based on each SNP, the test for CA19-9 identified patients with PDAC with 60.8% sensitivity and 98.8% specificity. Among patients with FUT3 alleles that encode a functional protein, levels of CA19-9 greater than the SNP-determined cut-off values identified 66.4% of patients with PDAC, with 99.3% specificity. In the validation set, levels of CEA varied among patients with vs without SNP in FUT2, by blood group, and among smokers vs nonsmokers; levels of CA-125 varied among patients with vs without the SNP in GAL3ST2. The use of the SNPs to define the ranges of CEA and CA-125 did not significantly increase the diagnostic accuracy of the assays for these proteins. Combining data on levels of CA19-9 and CEA, CA19-9 and CA-125, or CA19-9 and thrombospondin-2 increased the sensitivity of detection of PDAC, but slightly reduced specificity. CONCLUSIONS:Including information on SNPs associated with levels of CA19-9, CEA, and CA-125 can improve the diagnostic accuracy of assays for these tumor markers in the identification of patients with PDAC. Clinicaltrials.gov no: NCT02000089.
10.1016/j.cgh.2019.10.036
Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer.
Journal of translational medicine
BACKGROUND:The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography-a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer. METHODS:Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information. RESULTS:Total RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II. CONCLUSIONS:MAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.
10.1186/s12967-024-05181-z
Serum chemokine CXCL8 as a better biomarker for diagnosis and prediction of pancreatic cancer than its specific receptor CXCR2, C-reactive protein, and classic tumor markers CA 19-9 and CEA.
Litman-Zawadzka Ala,Łukaszewicz-Zając Marta,Gryko Mariusz,Kulczyńska-Przybik Agnieszka,Mroczko Barbara
Polish archives of internal medicine
Introduction Novel biomarkers are critically needed to improve the management of patients with pancreatic cancer (PC). Objectives We aimed to evaluate the clinical usefulness of serum CXCL8 in relation to its specific receptor CXCR2 in the diagnosis and prediction of PC compared with classic tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) and C-reactive protein (CRP). Patients and methods The study included 76 subjects: 42 patients with PC and 34 healthy volunteers. Serum protein levels were measured by immunological methods. Results Serum CXCL8 and CXCR2 concentrations were significantly higher in PC patients compared with healthy controls, similarly to classic tumor markers and CRP. CXCL8 levels were significantly elevated in patients with lymph node metastasis compared with individuals without nodal involvement. The diagnostic sensitivity, accuracy, negative predictive value, and areas under the receiver operating characteristic curves for CXCL8 were higher than those for CXCR2, CRP, CA 19-9, and CEA. Moreover, serum CXCL8 was the only significant predictor of PC risk. Conclusions Our findings indicate the significance of the CXCL8-CXCR2 axis in the pathogenesis of PC. Serum CXCL8 is emerging as the strongest candidate for a potential PC biomarker among all proteins tested.
10.20452/pamw.4307