Circulating RNAs as new biomarkers for detecting pancreatic cancer

Table 1 Circulating RNA specifically deregulated in pancreatic cancer

Target candidate	Up/down	Sample	Number of patients	Extraction method	Quantification method	Target selection	Normalization	Potential value	Ref.
mRNA
CEA mRNA	Up	Whole blood	9 PK, 9 HC	AGPC	RT-PCR	Pre	ACTB	D	[16]
EGFR mRNA	Up	Serum	11 PK, 23 HC	N/A	RT-PCR	Pre	B2M	D	[33]
4GnT mRNA	Up	Whole blood	55 PK, 10 CP, 70 HC	RNeasy Mini kit	RT-PCR	Pre	GAPDH	D	[34]
COL6A3 mRNA	Up	Serum	44 PK, 46 BT, 30 HC	PureYield RNA Midiprep	qRT-PCR	Pre	GAPDH	D/P	[35]
miRNA
mIR-155	Up	Plasma	49 PK, 36 HC	TRIzol LS	Taqman	Pre	miR-16	D	[55]
miR-196a	Up							D
miR-21	Up							D
miR-210	Up							D
miR-155	Up	Pancreatic juice	16 PK, 5CP	mirVana PARIS kit	Taqman	Pre	miR-199 U6-snRNA	D	[68]
miR-21	Up							D
miR-196a	Up	Serum	35 PK, 15 CP, 15 HC	TRI Reagent BD	Taqman	Pre	cel-miR-39	D/P	[69]
miR-200a	Up	Serum	45 PK, 11 CP, 32 HC	mirVana miR isolation kit	Taqman	Pre	miR-16	D	[70]
miR-200b	Up							D
miR-210	Up	Plasma	11 PK, 14 HC	Boiling	Taqman	Pre	cel-miR-54	D	[71]
miR-18a	Up	Plasma	36 PK, 30 HC	mirVana PARIS kit	Taqman	Pre	synthetic reference panel	D/T	[72]
miR-16	Up	Plasma	140 PK, 111 CP, 68 HC	TRI Reagent BD	Taqman	Pre	cel-miR-39	D	[73]
miR-196a	Up							D
miR-185	Up	Serum	80 PK, 129 HC	TRIzol LS	Taqman	Sequence	serum volume	D	[74]
miR-191	Up							D
miR-20a	Up							D
miR-21	Up							D/P
miR-24	Up							D
miR-25	Up							D
miR-99a	Up							D
miR-1290	Up	Serum	41 PK, 38 BT, 35 CP, 19 HC	mirVana PARIS kit	Taqman	Taqman mA	miR-16	D	[75]
miR-221	Up	Plasma	47 PK, 30 HC	mirVana PARIS kit	Taqman	Pre	synthetic reference panel	D/T/P	[76]
miR-375	Down							D/T/P
miR-375	Up	Plasma	48 PK, 47 HC	Total RNA purification kit (Norgen)	Taqman	Affymetrix mA	cel-miR-39,cel-miR-54, cel-miR-238	D	[77]
miR-27a3p	Up	Whole blood	129 PK, 103 BT, 60HC	Trizol	Taqman	Sequence	U6 snRNA	D/S	[78]
miR-196a	Up	Serum	19 PK, 10 CP, 20 BT, 10 HC	miReasy RNA extraction kit	Taqman	Pre	miR-24	D	[79]
miR-196b	Up							D
miR-205	Up	Pancreatic juice	50 PK, 19 CP, 19 HC	TRIzol LS	Taqman	Agilent mA	U6 snRNA	D/P	[80]
miR-210	Up							D/P
miR-492	Up							D/P
miR-1427	Up							D/P
miR-22	Up	Plasma	11 PK, 11 HR, 11 HC	TRI Reagent BD	Taqman	custom mA	miR-3196	D	[81]
miR-642b	Up							D
miR-885-5p	Up							D
Multi gene index		Whole blood	409 PK, 25 CP, 312 HC	PAXgene blood RNA	Taqman	Taqman mA	ath-miR159a	D	[82]
miR-483-3p	Up	Plasma	32 PK, 12 BT, 30 HC	mirVana PARIS kit	Taqman	Pre	miR-16	D	[83]
miR-21	Up							D
snRNA
U2 snRNA	Up	Serum	80 PK, 129 HC	mirVana miR isolation kit	qRT-PCR	Agilent mA	cel-miR-54	D	[84]

Reference were searched in PubMed database using the following search terms: “pancreatic cancer”, “non-coding RNA”, and “circulating” or “serum” or “plasma” or “blood”. PK: Pancreatic cancer; BT: Benign tumor; CH: Chronic pancreatitis; HR: High-risk patients; HC: Healthy control; AGPC: Acid-guanidinium-phenol-chroroform method; N/A: Not available; Taqman: Taqman qRT-PCR; Pre: Previously reported in pancreatic cancer tissues; mA: MiRNA microarray; D: Diagnostic marker; P: Prognostic marker; S: Staging marker; T: Treatment marker.

Table 2 Other circulating non-coding RNAs detected in cancer patients

Target candidate	Up/down	Cancer type	Sample	Number of patients	Extraction method	Quantification method	Normalization	Target selection	Ref.
Small ncRNA
SNORD33/66/76	Up	Lung	Plasma	37 Ca, 26 HR, 22 HC	mirVana miR isolation kit	SYBR qRT-PCR	U6 snRNA	mA	[93]
piR-651	Up	Gastric	Whole blood	93 Ca, 32 HC	TRizol	SYBR qRT-PCR	U6 snRNA	Pre	[94]
piR-823	Up
U2snRNA	Up	Pancreatic	Serum	80 Ca, 129 HC	mirVana miR isolation kit	qRT-PCR	cel-miR-54	mA	[84]
U2snRNA	Up	Colorectal		132 Ca, 129 HC
U2snRNA	Up	Lung	Serum	62 Ca, 51 BT, 45 HC	miRNeasy mini kit	LNA qRT-PCR	cel-miR-39	mA	[96]
U2snRNA	Up	Ovarian	Serum	119 Ca, 35 HC	mirVana PARIS kit	qRT-PCR	cel-miR-54	mA	[97]
Long ncRNA
H19	Up	Gastric	Plasma	43 Ca, 34 HC	N/A	pre-amplification qRT-PCR	N/A	Pre	[107]
MALAT1	Up	Prostate	Plasma	87 Ca, 82 HR, 23HC	mirVana PARIS kit	Taqman	Input amount	Pre	[108]
HULC	Up	Hepato-cellular	Plasma	30 Ca, 20 HC	TRIzol	qRT-PCR	GAPDH	Pre	[110]
TUG1 lincRNA	Up	Multiple myeloma	Plasma	62 MM, 40 HC	TriPure	qRT-PCR	GAPDH	Pre	[111]
LincRNA-p21	Down	CLL		68 CLL, 40 HC

Reference were searched in PubMed using the following search terms: “cancer”, “non-coding RNA”or “snoRNA” or “snRNA” or “piRNA” or “lncRNA”, and “circulating” or “serum” or “plasma” or “blood”. lincRNA: Long intergenic noncoding RNA; CLL: Chronic lymphocytic leukemia; MM: Multiple myeloma; Ca: Cancer patients; BT: Benign tumor; HR: High-risk patients; HC: Healthy control; N/A: Not available; Taqman: Taqman qRT-PCR; Pre: Previously reported in cancer tissue; mA: MiRNA microarray.

Table 3 Non-coding RNAs specifically upregulated in pancreatic cancer tissue

Target candidate	Up/down	Sample	Number of patients	Extraction method	Quantification method	Normalization	Target selection	Potential value	Ref.
HOTAIR	Up	Tissue	36 PK, 36 HC	mirVana RNA isolation kit	qRT-PCR	GAPDH	Pre	P	[112]
MALAT-1	Up	Tissue	126 PK, 15 HC	TRIzol	qRT-PCR	N/A	Pre	D/P/S	[113]
MEG3	Up	Tissue	31 PNET, 7 HC	RNeasy	qRT-PCR	GAPDH	Pre	D	[114]
Gas5	Up	Tissue	23 PK, 23 AN	TRIzol	qRT-PCR	ACTB	Pre	D	[115]
HULC	Up		304 PK, 304 AN	TRIzol	qRT-PCR	GAPDH	Pre	D/P	[116]
LOC285194	Down	Tissue	85 PK, 85 AN	TRIzol	qRT-PCR	GAPDH	Pre	D/P	[117]
PPP3CB intronic lncRNA	Up	Tissue	11 PK, 7 metastasis	TRIzol	qRT-PCR	HMBS	mA	D/S	[118]
MAP3K1	Up
DAPK1	Up
BC008363	Up	Tissue	30PK, 30 AN				mA	D/P	[119]
ENST00000480739	Down		35 PK, 35 AN	TRIzol	qRT-PCR	ACTB	mA	D/P	[120]
HSATII	Up	Tissue	11 PK, 2 HC	TRIzol	Sequence	Input amount	Sequence	D/P	[121]

Reference were searched in PubMed using the following search terms: “pancreatic cancer”, “long non-coding RNA” or “lncRNA” or “ncRNA”. PK: Pancreatic cancer; AN: Adjacent normal tissue; HC: Healthy control; mA: cRNA microarray; N/A: Not available; Pre: Previously reported in cancer tissue or cell line; D: Diagnostic marker; P: Prognostic marker; S: Staging marker.