Evolving utility of exosomes in pancreatic cancer management

Table 1 Circulating biomarkers in pancreatic cancer

Biomarker	Type	Role in pancreatic cancer
CA19-9	Protein	Widely used biomarkers to aid in the diagnosis[4]
		Poor screening tool in asymptomatic patients
		Elevated in many benign gastrointestinal conditions as well as other malignancies, including pancreatitis, cirrhosis, cholangitis, and colorectal cancer[5]
		5%-10% of the caucasian population possesses a Lewis a-/b- genotype and thus does not express CA19-9
CEA	Glycoprotein	Elevated across several cancers[6]
		Non specific
		Inferior sensitivity of CEA compared to ca19-9[7]
CA125	Glycoprotein	Associated with ovarian cancer, CRC and cholangiocarcinoma[8]
		Superiority to CA19-9 in predicting resectability of PC, along with correlating with metastasis-associated disease burden
Anti-MUC1 antibody	Antibody	Anti-MUC1 antibody assays showed a sensitivity and specificity of 77% and 95%, respectively, in discriminating pancreatic cancer from pancreatitis[9]
CTCs	Tumour cells	CTCs had moderate diagnostic value in PC[10]
		Several studies have demonstrated isolation of CTCs regardless of stage among localized, locally advanced, or metastatic patients
		Conflicting evidence on CTC positivity is correlated with survivability
		In ombination with CA19-9, it was reported to have a superior sensitivity and specificity of 97.8% and 83.3% respectively, compared to when used in isolation[11]
		The presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity = 75.0%, specificity = 96.4%, AUROC = 0.867, 95%CI: 0.798-0.935, and P < 0.001)[12]
		A cut-off of ≥ 3 CTCs in 4 mL blood could differentiate between local/regional and metastatic disease (AUROC: 0.885; 95%CI: 0.800-0.969; and P < 0.001)
cfDNA	DNA	Plasma ctDNA quantification of hot-spot mutations in KRAS and GNAS are useful in predicting tumor burden in patients diagnosed with PC[13]
		Digital PCR provided accurate tumor-derived mutant KRAS detection in plasma in resectable PC and improved post-resection recurrence prediction compared to CA19-9[14]
		Detection of plasma cfDNA mutations and copy number alterations may be helpful in pancreatic cancer prognosis and diagnosis
		Its sensitivity and specificity in identification of clinically relevant KRAS mutations was 87% and 99% respectively[15]
Cell-free RNA	RNA	Higher expression of lncRNA MALAT1 has been shown to correlate with poorer PDAC survival[16]
		Several microRNAs have also been associated with PDAC (i.e., miR-21 and miR-155), and correlate with tumor stage or prognosis[17]
EVs	Exosomes	KRAS G12D mutations were identified in 7.4% of control patients, 67% of localized PDAC, 80% of locally advanced PDAC, and 85% of metastatic PDAC patients[18]
		GPC1 EVs could be detected in both pancreatic precursor lesions and pancreatic cancer, and could distinguish between any evidence of malignancy and healthy patients with an AUC of 1 (100% sensitivity, 100% specificity)[19]
		miRNA isolated from EVs revealed a cocktail of miRNAs (miR-1246, 4644, 3976, 4306) upregulated in 83% of pancreatic cancer derived EV
		Glypican-1 exosomes are a potential biomarker for PC

CA: Carbohydrate antigen; PDAC: Pancreatic ductal adenocarcinoma; PC: Pancreatic cancer; CEA: Carcinoembryonic antigen; CTCs: Circulating tumour cells; cfDNA: Cell-free DNA; EVs: Extracellular vesicles; AUROC: Area under the curve.