TABLE 2.

Overall sensitivity and specificity of circulating miRNAs comparing to clinically standard biomarkers

miRNA	Standard biomarker	Sensitivity and specificity	Cases	Sample source	References
miR-27a “Upregulated”	CA15.3 CEA	miR-27a outperforms both CEA and CA15.3 in terms of early diagnosis of BC, with greater specificity and accuracy in detecting early stages BC patients.	100 BC patients, 30 benign breast lesions and 20 healthy volunteers	Human Serum	(Swellam et al., 2021)
miR-29a, miR-335 “Downregulated”	CEA CA15.3	The diagnostic fficiency of miR-29a and miR-335 outperformed CEA and CA 15.3, for early identification of BC patients.	44 BC patients, 25 benign breast lesions and control group served as 19 healthy volunteers	Human serum	(Ali Ahmed et al., 2020)
miR‐15b, miR‐21, miR‐29a, miR‐141, miR‐17‐3p “Upregulated”	CA19.9 CEA	miR-15b, miR-21, and miR-29a performed best in detecting early-onset colorectal cancer events, while miR-141 and miR-17-3p performed poorly and only upregulated at late stage	Male CD‐1 mice with induced colorectal carcinogenesis	Mice serum	(El-Daly, Morsy, et al., 2019a)
miR-21 “Upregulated”	AFP	miR-21 outperformed α-fetoprotein in distinguishing HCC from chronic hepatitis.	126 patients with HCC, 30 patients with chronic hepatitis, and 50 healthy volunteers.	Plasma	(Tomimaru et al., 2012).
miR-122, miR-133a, and miR-124 “Upregulated”	ALT AST	miR-133a was more sensitive to the degree of liver or skeletal muscle damage than AST, while ALT and AST have better specificities for diagnosing and discriminating muscle and liver toxicities. miR-122 is a more diagnostically sensitive marker for identifying liver injury than ALT.	Male and female Sprague Dawley rats treated with liver or muscle toxicants.	Rats plasma	(Laterza et al., 2009)
miR-145, miR-150, miR-223, miR-636, miR-26b, miR-34a, miR-122, miR-126*, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885 “Downregulated”	CA19-9	The putative diagnosis efficiency was strengthened by combining both miRNAs panels and serum CA19-9	409 pancreatic cancer patients and 25 chronic pancreatitis patients, 312 blood donors as healthy	Human whole blood	(Schultz et al., 2014)
miR-18a, miR-181b, and miR-335 “Upregulated”	CEA CA19-9	This miRNA profile outperformed currently used blood markers in terms of diagnostic accuracy for the early diagnosis of gastric cancer, including individuals with stage I tumor.	598 gastric cancer patient	Serum	(Izumi et al., 2021).
miR-21 “Upregulated”	CA15.3 CEA	miR-21 showed higher sensitivity over standard markers in the diagnosis of BC	89 BC patients and 55 healthy controls	Serum	(Gao et al., 2013)
miR-155 “Upregulated”	CA15.3 CEA	miR-155 showed a higher sensitivity over standard markers in the diagnosis of BC patients	184 BC patients and 75 control individuals	Serum	(Wang et al., 2014b)
miR-182, miR-183, miR-210 “Regulated according to tumor stage”	CEA	The diagnostic value of CEA was not significantly different from those of miRNAs	112 Non-small cell lung carcinoma patients and 104 controls	Serum	(Zhu et al., 2016)
miR-371a-3p	AFP LDH HCG	miR-371a-3p showed higher sensitivity than AFP, LDH and HCG	616 patients with testicular GCTs and 258 male controls	Serum	(Dieckmann et al., 2019)
miR-16, miR-195, and miR-199a “Downregulated”	AFP, DCP AFP-L3	miR-16 had the highest sensitivity for HCC, followed by miR-199a, AFP, DCP, AFP-L3, and miR-195	105 HCC patients, 107 CLD patients, and 71 healthy control	Serum	(Qu et al., 2011)
miR-122 and miR-155 “Upregulated”	ALB AST ALT	miR-122 levels were employed to predict treatment outcome with greater AUC, higher sensitivity, and specificity ratios compared with traditional biomarkers.	80 HCV patients	Serum	(Fan et al., 2017)