Table 2.

Studies assessing miRNAs expression in colorectal tumor tissue and nontumor tissue

Ref.Author(s), yearStudy populationMethodsNormalization controlsmiR
CountryCRC (stage I/II/III/IV)/adenoma tissueNontumor tissueAge mean (range)Tested miRs (No.)Significant miRs (No.)Difference between CRC tissue and nontumor tissue
23Kulda et al., 2010Czech Republic46 CRC (10/21/13/2)46 MNATa62.8 (39.9–79.1)TaqMan MicroRNA AssaysRNU6B22miR-21↑P < 0.0001
miR-143↓P < 0.0001
30 colorectal liver metastases30 MNAT59.4 (median; 39.6–82.1)miR-191miR-21↑P < 0.0001
miR-143↓P < 0.0001
24Chiang et al., 2011China107 CRC107 MNAT62.1 (17–82)SYBR green qRT-PCRRNU6B11miR-203↓P < 0.001
25Earle et al., 2010United States55 CRC (5/23/18/1)55 MNAT51.3 (25–85)TaqMan MicroRNA AssaysCt method2420miR-17↑ P = 4.38×10−4miR-135a↑ P = 1.12 ×10−3miR-26b↓ P = 8.91×10−9
miR-20a↑ P = 1.52×10−4miR-183↑ P = 2.47 ×10−16miR-143↓ P = 2.47×10−8
miR-25↑ P = 3.92×10−7miR-203↑ P = 3.14 ×10−3miR-145↓ P = 9.39×10−8
miR-31↑ P = 6.02×10−13miR-223↑ P = 3.69 ×10−2miR-191↓ P = 3.71×10−6
miR-92↑ P = 1.96×10−6miR-192↓ P = 3.51×10−16
miR-93↑ P = 3.33×10−5let-7a↓ P = 4.93×10−4miR-196a↓ P = 7.72×10−4
miR-133b↑ P = 1.36×10−2miR-16↓ P = 1.78×10−3miR-215↓ P = 2.37×10−13
26Li et al., 2010China66 CRC (17/18/22/9)66 MNAT-SYBR green qRT-PCRRNU6B11miR-126↓P < 0.001
27Liu et al., 2010China81 CRC81 MNAT57.4qRT-PCRRNU6B -11miR-195 ↓P < 0.01
28Wang et al., 2010China3 colonic tumor tissue3 MNAT-microRNA microarray andTaqMan MicroRNA Assays72314bmiR-18a↑miR-135b↑miR-374a↑
miR-18b↑miR-196b ↑miR-424↑
miR-19a ↑miR-224 ↑miR-378↓
miR-20a* ↑miR-301b↑miR-378*↓
miR-106b ↑miR-335 ↑(miR-18a,135b were validated by qRT-PCR)
29Wang et al., 2009China98 (I+II 45/III+IV 53)98 MNAT54.3TaqMan MicroRNA Assays5S rRNA32miR-31↑P = 0.001
(24–83)miR-145↓P = 0.001
30Diosdado et al., 2009The Netherlands55 (30 adenomas 25 adenocar- cinomas)10 normal mucosaCase 68.4 (47–88)TaqMan MicroRNA AssaysRNU4866miR-17↑ P = 0.001miR-19b-1↑ P = 0.021
Control 68miR-18a↑ p = 0.04miR-20a ↑ P = 0.001
miR-19a↑ P < 0.001miR-92a-1↑ P < 0.001
31Sarver et al., 2009United States80 colon cancer28 normal colon tissue-SYBR green qRT-PCRRNU6B73539miR-17–3p↑ P = 7.59 ×10−14miR-552↑ P = 1.72×10−8miR-138↓ P = 0
miR-31↑ P = 0miR-584 ↑ P = 0miR-139↓ P = 0
miR-32 ↑ P = 1.97×10−5HS_287 ↑ P = 3.87×10−8miR-147↓ P = 0
miR-33 ↑ P = 1.76×10−9HS_29 ↑ P = 1.91×10−9miR-328↓ P = 2.62×10−14
miR-96 ↑ P = 7.11×10−14miR-1↓ P = 2.33×10−11miR-363↓ P = 1.30×10−7
miR-135b↑ P = 0miR-9↓ P = 0miR-375↓ P = 0
miR-182 ↑ P = 0miR-9*↓ P = 0miR-378↓ P = 0
miR-182*↑ P = 0miR-10b↓ P = 2.66×10−15miR-486↓ P = 6.90×10−9
miR-183 ↑ p = 0miR-20b↓ p = 1.90×10−7miR-497↓ P = 0
miR-188 ↑ P = 1.20×10−11miR-30a-3p↓ P = 0miR-511↓ P = 2.22×10−16
miR-224 ↑ P = 0miR-30a-5p↓ P = 0miR-551b↓ P = 0
miR-503 ↑ P = 0miR-133a↓ P = 9.55×10−15miR-642↓ P = 0
miR-542–5p↑ P = 7.01×10−11miR-137↓ P = 0miR-650↓ P = 0
(P < 10−16 represent as 0)
32Arndt et al., 2009United States45 (4/19/20/2) CRC4 normal colon tissueCRC 62.8TaqMan MicroRNA AssaysA no cDNA control16937miR-18a↑ P = 2.9×10−3miR-106a↑ P = 5.1×10−4miR-125a↓ P = 6.40×10−3
Control -miR-19a↑ P = 2.3×10−3miR-106b↑ P = 1.0×10−4miR-30a-3p↓ P = 7.30×10−4
miR-19b↑ P = 3.4×10−3miR-130b↑ P = 1.2×10−3miR-30a-5p↓ P = 1.60×10−5
miR-20a↑ P = 2.0×10−3miR-17–5p↑ P = 1.5×10−3miR-30c↓ P = 4.00×10−4
miR-21↑ P = 6.0 x 10−6miR-181b↑ P = 2.2×10−4miR-133a↓ P = 6.50×10−4
miR-25↑ P = 1.4×10−2miR-182↑ P = 2.8×10−3miR-139↓ P = 1.10×10−5
miR-29a↑ P = 3.6×10−4miR-183↑ P = 2.3×10−3miR-143↓ P = 1.00×10−2
miR-29b↑ P = 4.9×10−3miR-203↑ P = 2.2×10−2miR-145↓ P = 1.20×10−3
miR-31↑ P = 2.6×10−3miR-224↑ P = 1.1×10−3miR-195↓ P = 4.20×10−5
miR-34a↑ P = 1.5×10−2miR-378*↓ P = 1.30×10−5
miR-93↑ P = 3.4×10−3miR-422a↓ P = 7.30×10−5
miR-95↑ P = 1.1×10−2miR-1↓ P = 1.6×10−3miR-422b↓ P = 8.30×10−5
miR-96↑ P = 8.4×10−3miR-10b↓ P = 2.1×10−2miR-497↓ P = 9.80×10−4
33Chen et al., 2009China13 CRC13 MNAT57.2qRT-PCR-20015miR-31↑ P = 0.016miR-200a↑ P = 0.036miR-145↓ P = 0.048
miR-92↑ P = 0.049miR-200c↑ P = 0.033miR-192↓ P = 0.008
miR-103↑ P = 0.002miR-210↑ P = 0.000miR-193b↓ P = 0.006
miR-142-3p↑ P = 0.016miR-125b↓ P = 0.010miR-212↓ P = 1.88×10−9
miR-188↑ P = 0.001miR-143↓ P = 0.001miR-214↓ P = 5.95×10−7
34Schmitz et al., 2009Germany18 SSAs20 Normal colonic mucosalSSAs 60.1TaqMan MicroRNA AssaysRNU4843miR-21 ↑P < 0.001
CRC -miR-181b ↑P < 0.001
20 CRCControl -miR-181b ↑P < 0.001
miR-133↓P = 0.025
35Motoyama et al., 2008Japan69 CRC69 MNAT-MicroRNA microarray and TaqMan MicroRNA AssaysRNU6B4558miR-17–5p ↑ P < 0.05miR-92 ↑ P < 0.05
miR-18a ↑ P < 0.05miR-183 ↑ P < 0.05
miR-31 ↑ P < 0.05miR-143↓ P < 0.05
miR-20a ↑ P < 0.05miR-145↓ P < 0.05
36Schetter et al., 2008United States (test cohort)/China (validation cohort)197 primary colon tumorc197 MNATcTest cohort 64.6 (32–87)MicroRNA microarray and TaqMan MicroRNA AssaysRNU6B3895miR-20a ↑P < 0.001
Validation cohort 55.8 (32–84)miR-21 ↑P < 0.001
miR-106a ↑P < 0.001
miR-181b ↑P < 0.001
miR-203 ↑P < 0.001
Cooperative Human Tissue Network18 adenoma18 MNAT-TaqMan MicroRNA Assays51miR-21 ↑P = 0.006
37Slaby et al., 2007Czech Republic29 CRC (3/11/6/9)6 Nontumor adjacent tissueCRC 65 (median; 49–75)TaqMan MicroRNA Assayslet-7a-144miR-21↑P = 0.0001
Control -miR-31↑P = 0.0006
miR-143↓P = 0.011
miR-145↓P = 0.003
38Schepeler et al., 2008Denmark49 colon cancers (stage II)10 normal mucosaCase 65.7 (36–87)LNA-based oligonucleotide microarrays and TaqMan MicroRNA Assays-31519dmiR-20a↑miR-302a↑miR-510↑miR-527↑miR-101↓
Control 67.4 (52–85)miR-92↑miR-320↑miR-512–5p↑miR-145↓
miR-191*↑miR-432*↑miR-513↑miR-26b↓miR-455↓
miR-200a*↑miR-492↑miR-526c↑miR-30b↓miR-484↓
39Monzo et al., 2008Spain22 (6 is stage I and 16 is stage II)22 MNAT69.5 (49–87)TaqMan MicroRNA Assayslet-7a15628e (6 stage I vs. MNAT)miR-17–5p↑miR-92↑miR-135b↑miR-203↑miR-99a↓
miR-19a↑miR-95↑miR-148a↑miR-224↑miR-125b↓
miR-20↑miR-96↑miR-182↑miR-339↑miR-139↓
miR-21↑miR-103↑miR-182*↑miR-145↓
miR-31↑miR-106a↑miR-183↑miR-149↓
miR-34a↑miR-107↑miR-200c↑miR-30a- 3p↓miR-195↓
64e (16 stage I vs. MNAT)let-7g↑miR-34a↑miR-141↑miR-183↑miR-221↑
miR-10a↑miR-92↑miR-142–3p↑miR-186↑miR-222↑
miR-15a↑miR-95↑miR-142–5p↑miR-191↑miR-224↑
miR-15b↑miR-96↑miR-146↑miR-194↑miR-301↑
miR-17–3p↑miR-98↑miR-147↑miR-197↑miR-320↑
miR-17–5p↑miR-103↑miR-148a↑miR-200a↑miR-324–5p↑
miR-19a↑miR-105↑miR-151↑miR-200b↑miR-330↑
miR-20↑miR-106a↑miR-154*↑miR-200c↑miR-338↑
miR-21↑miR-122a↑miR-181a↑miR-210↑miR-339↑
miR-25↑miR-128a↑miR-181b↑miR-213↑miR-370↑
miR-27a↑miR-130b↑miR-181c↑miR-215↑miR-373↑
miR-29a↑miR-134↑miR-182↑miR-216↑miR-374↑
miR-31↑miR-135a↑miR-182*↑miR-219↑
40Volinia et al., 2006United States and Italy46 colon tumor8 normal tissue-MicroRNA microarray-22822fmiR-10a ↑miR-24–2 ↑miR-106a ↑miR-155 ↑miR-223↑
miR-17-5p↑miR-29b-2↑miR-107↑miR-191 ↑
miR-20a ↑miR-30c↑miR-126*↑miR-203↑miR-9–3 ↓
miR-21↑miR-32 ↑miR-128b ↑miR-213↑
miR-24-1 ↑miR-99b ↑miR-150 ↑miR-221↑
41Nakajima et al., 2006United States and Japan21 CRC21 MNAT-SYBR green qRT-PCR5s rRNA RNU6B53let-7g↑ P = 0.0037miR-181b↑ P = 0.0005miR-200c↑ P = 0.0001
42Xi et al., 2006Germany24 CRC (4/4/8/8)24 MNAT62 (30–93)SYBR green qRT-PCR5S rRNA104miR-15b↑ P = 0.0278miR-191↑ P = 0.0264
miR-181b↑ P = 0.0002miR-200c↑ P = 0.0017
  • aMNAT: matched nontumor adjacent tissue.

  • bP values less than 0.1, details are not available.

  • c84 patients with colon tumors in the U.S. test cohort and 113 patients with colon tumors in the Hong Kong validation cohort.

  • dDifferentially expressed miRNAs identified by significance of microarray analysis (SAM). The cutoff, delta value, was adjusted so as to set the median false discovery rate (FDR) < 0.0001%.

  • eSAM and Student's t test were done to identify differentially expressed miRNAs with a FDR < 0.1.

  • fSAM and Student's t test were done to identify differentially expressed miRNAs with a FDR ≤ 0.01.