Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review

Yang, Jinshou; Xu, Ruiyuan; Wang, Yuming; Qiu, Jiangdong; Ren, Bo; You, Lei

doi:10.1002/cac2.12204

Cited by 131 publications

(84 citation statements)

References 135 publications

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“…Although other cancers were not evaluated, it is possible that some individuals who carried GPV in a cancer predisposition gene would not have been ascertained through a traditional phenotype-first approach in the clinic due to a lack of personal or family history of cancer. Furthermore, individuals with GPV, especially in high-risk genes, could possibly benefit from innovative technologies in early PDAC screening, including circulating tumor DNA, exosomes in blood, artificial intelligence, metabolomics, and ion mobility spectrometry, which have shown promising prospects [34].…”

Section: Discussionmentioning

confidence: 99%

A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes

Astiazaran-Symonds

Kim

Haley

et al. 2022

Cancers

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Patients with germline pathogenic variants (GPV) in cancer predisposition genes are at increased risk of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The genes most frequently found to harbor GPV in unselected PDAC cases are ATM, BRCA1, BRCA2, CDKN2A, CHEK2, and PALB2. However, GPV prevalence and gene-specific associations have not been extensively studied in the general population. To further explore these associations, we analyzed genomic and phenotypic data obtained from the UK Biobank (UKB) and Geisinger MyCode Community Health Initiative (GHS) cohorts comprising 200,600 and 175,449 participants, respectively. We estimated the frequency and calculated relative risks (RRs) of heterozygotes in both cohorts and a subset of individuals with PDAC. The combined frequency of heterozygous carriers of GPV in the general population ranged from 1.22% for CHEK2 to 0.05% for CDKN2A. The frequency of GPV in PDAC cases varied from 2.38% (ATM) to 0.19% (BRCA1 and CDKN2A). The RRs of PDAC were elevated for all genes except for BRCA1 and varied widely by gene from high (ATM) to low (CHEK2, BRCA2). This work expands our understanding of the frequencies of GPV heterozygous carriers and associations between PDAC and GPV in several important PDAC susceptibility genes.

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Section: Discussionmentioning

confidence: 99%

A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes

Astiazaran-Symonds

Kim

Haley

et al. 2022

Cancers

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“…[80][81][82] Due to its asymptomatic course, rapid progression, and delayed clinical presentation, PDAC is considered a silent killer, and most patients were diagnosed at an advanced stage. 83,84 Early detection of PDAC at resectable stages has profound impact on changing the malignancy's poor survival figures. 85,86 However, no reliable screening method, either molecular or imaging-based, exists to date to allow accurate early detection of asymptomatic PDAC patients.…”

Section: Discussionmentioning

confidence: 99%

One-Pot Endonucleolytically Exponentiated Rolling Circle Amplification by CRISPR-Cas12a Affords Sensitive, Expedited Isothermal Detection of MicroRNAs

Wen

Han

et al. 2022

Preprint

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MicroRNAs (miRNAs) are a class of short non-coding RNAs that play essential roles in gene expression regulation. While miRNAs offer a promising source for developing potent cancer biomarkers, the progress towards clinical utilities remains largely limited, due in part to the long-standing challenge in sensitive, specific, and robust detection of miRNAs in human biofluids. Emerging next-generation molecular technologies, such as the CRISPR-based methods, promise to transform nucleic acid testing. The prevailing strategy used in existing CRISPR-based methods is to hyphenate two separate reactions for pre-amplification, e.g., rolling circle amplification (RCA), and amplicon detection by Cas12a/13a trans-cleavage in tandem. Thus, existing CRISPR-based miRNA assays require multiple manual steps and lack the analytical performance of the gold standard, RT-qPCR. Radically deviating from the existing strategies, we developed a one-step, one-pot isothermal miRNA assay termed “Endonucleolytically eXponenTiated Rolling circle Amplification with the dual-functional CRISPR-Cas12a” (EXTRA-CRISPR) to afford RT-PCR-like performance for miRNA detection. We demonstrated the superior analytical performance of our EXTRA-CRISPR assay to detect miRNAs (miR-21, miR-196a, miR-451a, and miR-1246) in plasma extracellular vesicles, which allowed us to define a potent EV miRNA signature for detection of pancreatic cancer. The analytical and diagnostic performance of our one-pot assay were shown to be comparable with that of the commercial RT-qPCR assays, while greatly simplifying and expediting the analysis workflow. Therefore, we envision that our technology provides a promising tool to advance miRNA analysis and clinical marker development for liquid biopsy-based cancer diagnosis and prognosis.

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“…The majority of patients are unresectable (75–80%) [ 20 , 21 , 22 , 23 ] and have a low 5-year overall survival rate [ 24 , 25 , 26 ]. CA19-9 is not recommended for screening early pancreatic cancer because of its limited sensitivity [ 27 , 28 , 29 ], especially in small tumors [ 30 ]. Hence, detection for early-stage PDAC and the evaluation of PDAC prognosis remain difficult problems.…”

Section: Discussionmentioning

confidence: 99%

Serum Nardilysin as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

Xu¹,

Xiong²,

Yang³

et al. 2022

JCM

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Background: Nardilysin, (N-arginine dibasic convertase, NRDC) has been reported to play an important role in cancer progression, and is associated with tumor proliferation signals and inflammatory signals, such as tumor necrosis factor-a (TNF-a) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), through the activation of disintegrin and metalloproteinase (ADAM) proteases. NRDC has recently been revealed to be involved in the tumorigenesis of various types of cancer, including intrahepatic cholangiocarcinoma, malignant cerebral infarction, esophageal squamous cell carcinoma, and gastric cancer. However, the expression profiles and biological relevance of NRDC in pancreatic ductal adenocarcinoma have rarely been reported. Methods: We analyzed the NRDC expression profile in pancreatic ductal adenocarcinoma by enzyme-linked immunosorbent assay (ELISA) and identified NRDC as a circulating biomarker in the serum of 112 pancreatic ductal adenocarcinoma patients. The diagnostic value of NRDC was analyzed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results demonstrated that the clinical prognosis significance of NRDC with the clinical characteristics in pancreatic ductal adenocarcinoma (PDAC). NRDC was notably decreased in PDAC patient serum compared with the control group (p < 0.001). Furthermore, the present study found that the NRDC expression level was correlated with T grade (p < 0.001), metastasis(p < 0.001), differentiation(p < 0.001), and TNM stage (p = 0.011). Further bioinformatics analysis revealed that NRDC correlated with proliferation and migration pathways; in particular, it mediated cell-matrix adhesion-dependent activation in pancreatic ductal adenocarcinoma. Conclusions: Serum NRDC may play a useful diagnostic biomarker to evaluate the aggressive clinical features in PAAD patients.

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Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review

Cited by 131 publications

References 135 publications

A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes

A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes

One-Pot Endonucleolytically Exponentiated Rolling Circle Amplification by CRISPR-Cas12a Affords Sensitive, Expedited Isothermal Detection of MicroRNAs

Serum Nardilysin as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

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