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. 2023 Mar 29;68(7):2811–2823. doi: 10.1007/s10620-023-07904-6

Table 1.

Blood biomarkers with possible clinical use in PDAC

Blood biomarkers Potential clinical use in PDAC
Proteins
 CA 19.9 Prognosis
Disease monitoring in clinical practice
It is not used for diagnosis in clinical practice due to a low sensitivity (78%) and specificity (83%)
 CEA Prognosis
 ADH and MIC-1 The addition of ADH and MIC-1 to CA 19.9 significantly improved the efficacy of diagnosis (AUC 0.89)
 SPARC/Osteonectin Detection of early stage (sensitivity 84.6%, specificity 87.5%)
 Panel of TIPM1, LRG1 and CA 19.9 Detection of early stage (sensitivity 84.9%, specificity 95%, AUC 0.949)
 IGFBP3 Detection of early stage (sensitivity 76.3%, specificity 70.7%); increased effectiveness as a compensatory biomarker for CA 19.9 (AUC 0.90)
 apoII-ATQ/AT Decline significantly in PDAC; combined with CA 19.9 as a sensitivity of 95.4% and specificity of 98.3%
Metabolites
 Five-metabolite panel (acetylspermidine, diacetylspermine, an indole derivate, and two lysophosphatidylcholines) Detection of early stage: performance was significantly improved when combined with the previously validated protein panel of CA 19.9, LRG1, and TIMP1 (AUC 0.924)
Circulating tumor DNA
 KRAS mutant ctDNA Diagnosis (sensitivity 47%, specificity 87%); combination with CA 19.9 had a sensitivity of 98% and specificity of 77%
Disease monitoring in advanced PDAC patients under chemotherapy
Prognosis
 cfDNA hypermethylation Diagnosis: ZNF154 cfDNA methylation discriminated cases from healthy donor plasma; integrated model of 5mC and 5hmC (AUC 0.997)
Prognosis
Circulating tumor cells
 CK-20, CEA, C-MET, and the human telomerase reserve transcriptase mRNA expression Diagnosis (CK-20: sensitivity 84%, specificity 93%; CEA: sensitivity 80%, specificity 100%; C-MET: sensitivity 80%, specificity 100%; human telomerase reverse transcriptase: sensitivity 100%, specificity 100%)
Disease monitoring
 CEA mRNA expression Prognosis
 CTC numbers Disease monitoring
Prognosis
Circulating miRNA  See Table 2
Circulating exosomes
 Circulating exosomes positive for GPC1 Diagnosis
Disease monitoring
Prognosis
 KRAS mutations from exosomes Diagnosis: identified in 66.7%, 80%, and 85% of patients with localized, locally advanced, and metastatic disease, respectively
Prognosis
 MUC5AC Diagnosis: can predict the presence of invasive carcinoma within IPMN (sensitivity 82%, specificity 100%)

CA 19.9 Carbohydrate antigen 19.9, CEA Carcinoembryonic antigen, AHD Alcohol dehydrogenase, MIC-1 Circulating macrophage inhibitory cytokine, SPARC Secreted protein acidic and rich in cysteine, TIPM1 tissue inhibitor of metalloproteinase-1, LRG1 leucine-rich alpha-2 glycoprotein 1, IGFBP3 Insulin-like growth factor-binding protein 3, apoII-ATQ/AT C-terminal truncations of the circulating apolipoprotein

AII homo-dimer—ctDNA circulating tumor DNA, cfDNA cell-free DNA, 5mC 5-methylcytosine, 5hmC 5-hydroxymethylcytosine, GPC1 glypican-1