MicroRNAs as lung cancer biomarkers

Table 1 MiRNAs from resected samples as biomarkers for the diagnosis of lung cancer

MiRNA	Scope	Sample	Ref.
mir-21, mir-191, mir-210, mir-155, mir-205, mir-24-2, mir-212, mir-214, mir-17-3p, mir-106a, mir-197, mir-192, mir-146, mir-203, mir-150, (UP) mir-126-5p, mir-143, mir-192-prec, mir-224, mir-126, mir-30a-5p, mir-140, mir-9, mir-124a-1, mir-218-2, mir-95, mir-145, mir-198, mir-216-prec, mir-219-1, mir-125a-prec, mir-26a-1-prec, mir-199b-prec, let-7a-2-prec, mir-27b, mir-32, mir-29b-2, mir-220, mir-33, mir-181c-prec, mir-101-1, mir-124a-3, mir-125a (DOWN)	Lung cancer vs normal	Solid (Not specified)	[28]
mir-21, mir-191, mir-155, mir-210, mir-24-2 (UP) mir-126-5p, mir-126-3p, mir-219-1, mir-95, mir-192-prec, mir-220, mir-216-prec, mir-204-prec, mir-188, mir-198, mir-145, mir-224 (DOWN)	ADs vs normal	Solid (Not specified)	[28]
mir-205, mir-191, mir-210, mir-17-3p, mir-203, mir-155, mir-21, mir-214, mir-212, mir-197 (UP) mir-224, mir-126*, mir-140, mir-29b, mir-143, mir-30a-5p (DOWN)	SCC vs normal	Solid (Not specified)	[28]
miR-31 (UP) miR-107, miR-185, let-7a (DOWN)	Lung cancer tissue vs normal	Solid (Not specified)	[70]
miR-26a, let-7g, let-7f, miR-98, miR-29a, let-7c, miR-30b, let-7i, let-7b, miR-29b, miR-26b, let-7a, miR-146b-5p, miR-195, miR-29c, miR-30d, miR-20a, miR-17, miR-19b, miR-106a, miR-16, let-7d, miR-106b, miR-181a, miR-498, miR-103, miR-107, miR-191, mir-663, miR-491-5p, let-7e, mir-654-5p (UP) miR-453, miR-509-3p (DOWN)	AD vs SCC; male smokers patients	Solid, formalin-fixed, paraffin-embedded	[71]
miR-17-5p, miR-20a, miR-20b, miR-93, miR-106a, miR-106b, miR-182, miR-183, miR-200a, miR-200c, miR-203, miR-210, miR-224 (UP) miR-125a, let7e (DOWN)	SCC vs normal	Solid, Snap-frozen	[72]
miR-30a, miR-140-3p, miR-182, miR-210, miR-486-5p	Stage I-III vs normal	Solid, Snap-frozen	[73]
miR-182, miR-200c, miR-141, miR-375, miR-7, miR-429, miR-200a, miR-370, miR-200b, miR-382 (UP) miR-126, miR-451, miR-195, miR-486-5p, miR-214, miR-199a-5p (DOWN)	Primary lung tumors vs metastases	Solid, formalin-fixed, paraffin-embedded	[74]
miR-205, miR-21 (relative expression)	AD vs SCC	Solid, formalin-fixed, paraffin-embedded	[75]
miR-21, miR-155 (UP)	LCNECs and SCLCs vs TCs and ACs	Solid, formalin-fixed, paraffin-embedded	[79]
miR-205, miR-27a, miR-29a, miR-29b, miR-34a (DOWN in NSCLC) miR-25, miR-375 (UP in NSCLC)	SCLC vs NSCLC	Solid, formalin-fixed, paraffin-embedded	[80]
miR-29a, miR-29b, miR-34a, miR-375 (DOWN in SQ) miR-205, miR-25, miR-27a (UP in SQ)	SCC vs AD	Solid, formalin-fixed, paraffin-embedded	[80]
miR-7, miR-21, miR-29b, miR-106a, miR-125a-5p, miR-129-3p, miR-205, miR-375 (relative expression)	Carcinoid, SCLC, and squamous and nonsquamous NSCLC	Solid, Fresh Biopsy	[81]
miR-21, miR-155, miR-7 (UP)	Tumor vs normal	Solid, fine-needle aspirate (FNA)	[82]
miR-21, miR-155 (UP)	NSCLC vs normal	Sputum	[96]
miR-205, miR-210, miR-708 (relative expression)	SCC vs normal	Sputum	[97]
miR-21, miR-200b, miR-375 and miR-486 (relative expression)	AD vs Normal	Sputum	[98]
miR-31, miR-210 (relative expression)	Stage I NSCLC vs normal	Sputum	[99]
miR-31, miR-210 (Relative Expression) + computed tomography	Stage I NSCLC vs normal	Sputum	[100]

AD: Adenocarcinoma; SCC: Squamous cell carcinoma; LCNEC: Large cell neuroendocrine carcinoma; SCLC: Small cell lung carcinoma; TC: Typical carcinoid; AC: Atypical carcinoid; NSCLC: Non-small cell lung cancer.

Table 2 MiRNAs as biomarkers for the prognosis and to predict response to therapy

miRNA	Experiment	Scope	Sample	Ref.
let-7a family (DOWN)	lung cancer tissue vs normal	NSCLC poor postoperative survival	Solid, (not specified)	[26]
mir-155, mir-17-3p, mir-106a, mir-93, mir-21 (UP) let-7a-2, let-7b (DOWN)	AD vs SCC	AD poor survival	Solid, (not specified)	[28]
miR-221, let-7a (DOWN) miR-137, miR-182-3p, miR-372 (UP)	NSCLC vs normal	NSCLC poor survival	Solid, snap frozen	[83]
miR-146b, miR-191, miR-155, miR-15a, miR-511, miR-100, miR-10a, miR-21, miR-126 (UP) miR-206, miR-299-3p, miR-122a, miR-513, miR-184, miR-453, miR-379, miR-202, miR-494, miR-432, miR-370 (DOWN)	SCC vs normal	SCC Overall Survival	Solid, snap frozen	[72]
miR-34a (DOWN)	NSCLC vs normal	NSCLC Probability of relapse	Solid, (not specified)	[84]
mir-124-5p, mir-146b-3p, mir-200b-5p, mir-30c-1-3p, mir-510, mir-585, mir-630, mir-657, mir-708 (relative expression)	stage I NSCLC vs normal	Stage I NSCLC recurrence	Solid, formalin-fixed, paraffin-embedded (FFPE)	[64]
miR-16 (UP)	NSCLC vs normal	NSCLC poor survival	Solid, (not specified)	[86]
miR-143 (DOWN)	Lung cancer tissue vs normal	smoking status	Solid, snap frozen	[88]
miR-21 (UP) miR-181a (DOWN)	Lung cancer tissue vs normal	NSCLC poor survival	Solid, snap frozen	[88]
miR-25, miR-34c-5p, miR-191, let-7e, miR-34a (DOWN)	AD vs SCC	SCC survival	Solid, formalin-fixed, paraffin-embedded (FFPE)	[71]
miR-31 (UP)	SCC vs normal	SCC poor survival	Solid, snap frozen	[73]
miR-325, miR-326, miR-328, miR-329-2-pre, miR-330-3p, miR-500a-3p, miR-370, miR-650-pre (UP)	BM − NSCLC vs BM + NSCLC	NSCLC, risk for brain metastasis	Solid, formalin-fixed, paraffin-embedded (FFPE)	[89]
miR-21 (UP)		Platinum-based chemotherapy-resistant NSCLC patients	Solid, snap frozen	[90]
miR-196a-2 SNP	Treatment vs genotype	Severe toxicity after platinum-based chemotherapy of advanced NSCLC patients	Genomic DNA from peripheral leukocytes	[91]
miR-128b (UP)		NSCLC samples correlated with clinical response and survival following gefitinib treatment	Microdissected primary surgically resected NSCLC tumors	[92]
miR-30b, miR-30c		Regulated by EGFR and hepatocyte growth factor (MET) receptor tyrosine kinase	Solid, Lung tumor tissue samples	[93]
miR-30b, miR-30c		Prognostic predictors in NSCLC patients who underwent first line treatment with TKIs	Solid, formalin-fixed, paraffin-embedded (FFPE)	[94]

NSCLC: Non-small cell lung cancer; AD: Adenocarcinoma; SCC: Squamous cell carcinoma; BM: Brain metastasis.

Table 3 Circulating miRNAs as biomarkers in lung cancer

MiRNA	Function	Scope	Sample	Ref.
miR-155, miR-197, miR-182 (UP)	Diagnostic	Lung cancer patients vs healthy controls	Plasma	[126]
miR-21, miR-210, miR-126, miR-486-5p (relative expression)	Diagnostic	NSCLC patients vs healthy controls	Plasma	[127]
miR-21–5p (UP) and miR-335–3p (DOWN)	Diagnostic	Lung cancer patients vs healthy controls	Plasma	[128]
miR-21, miR-155 (UP), miR-145 (DOWN)	Diagnostic	Lung cancer patient vs healthy smokers	Plasma	[129]
miR-361-3p, miR-625* (DOWN)	Diagnostic	Lung cancer patients vs healthy controls	Serum	[130]
miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a (DOWN), miR-29c (UP)	Diagnostic	Early stage NCSLC vs healthy controls	Serum	[131]
miR-92a, miR-484, miR-486-5p, miR-328, miR-191, miR-376a, miR-342, miR-331-3p, miR-30c, miR-28-5p, miR-98, miR-17-5p, miR-26b, miR-374, miR-30b, miR-26a, miR-142-3p, miR-103, miR-126, let-7a, let-7d, let-7b, miR-22, miR-148b, miR-139 (DOWN), miR-32, miR-133b, miR-566, miR-432-3p, miR-223, miR-29a, miR-148a, miR-142-5p, miR-140-5p (UP)	Diagnostic	Asymptomatic NSCLC patients vs healthy smokers	Serum	[132]
miR-205-5p, miR-205-3p, and miR-21-3p (UP)	Diagnostic	NSCLC patients vs benign lung disease and healthy controls	Serum	[133]
miR-190b, miR-630, miR-942 and miR-1284 (relative expression)	Diagnostic	Lung cancer patients vs healthy controls	Whole-blood	[85]
miR-22, miR-24, and miR-34a (UP)	Diagnostic	NSCLC patients vs healthy controls	Whole-blood	[134]
miR-205, miR-19a, miR-19b, miR-30b, miR-20a (DOWN)	Diagnostic	Patients after lung cancer surgery vs healthy controls	Plasma	[135]
miR-7, miR-21, miR-200b, miR-210, miR-219-1, miR-324 (UP), miR-126, miR-451, miR-30a, miR-486 (DOWN)	Diagnostic	NSCLC patients vs healthy controls	Plasma	[137]
miR-101, miR-106a miR-126, miR-133a, miR-140-3p, miR-140-5p, miR-142-3p, miR-145, miR-148a, miR-15b, miR-16, miR-17, miR-197, miR-19b, miR-21, miR-221, miR-28-3p, miR-30b, miR-30c, miR-320, miR-451, miR-486-5p, miR-660, and miR-92a (relative expression)	Diagnostic	NSCLC patients vs healthy controls	Plasma	[138]
miR-155, miR-197 (UP)	Prognostic	Lung cancer patients with metastasis vs patients without metastasis	Plasma	[126]
miR-486, miR-30d, miR-1, miR-499 (relative expression)	Prognostic	NSCLC patients vs healthy controls	Serum	[139]
let-7f, miR-30e-3p (DOWN)	Prognostic	NSCLC patients vs healthy controls	Plasma	[140]
miR-125b (relative expression)	Prognostic	NSCLC patients vs healthy controls	Serum	[141]
miR-21 (UP)	Response to treatment	Platinum chemotherapy-resistant patients vs non resistant patients	Plasma	[90]
miR-21 and miR-10b (UP)	Response to treatment	NSCLC patients with EGFR mutation vs patients without mutation	Plasma	[142]
miR-22 (UP)	Response to treatment	NSCLC patients vs healthy controls	Whole-blood	[134]

NSCLC: Non-small cell lung cancer.