MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside

Table 1 A list of representative miRNAs identified in tumor tissues that are of prognostic value in colorectal cancer patients

miRNA	Method of detection	Patient number	Observations and correlation with clinical outcome	Ref.
miR-15a/miR-16	qRT-PCR	126	miR-15a/miR-16 downregulation were significantly associated with advanced TNM staging, poorly histological grade, positive lymph node metastasis. miR-15a/miR-16 combination were identified as independent predictors of unfavorable OS and DFS	[183]
miR-17-5p	qRT-PCR	110	High expressions were associated with pathological tumor features of poor prognosis. miR-17-5p correlated with DFS only at early stages	[184]
miR-21	In situ hybridization	84	High miR-21 expressions were strongly associated with poor survival, more advanced TNM staging and poor therapeutic outcome	[90]
miR-29a	miRNA microarray, qRT-PCR	110	High expressions were associated with a longer DFS in CRC patients with stage II but not in stage I tumor	[61]
miR-34a-5p	qRT-PCR	205	The tissue expressions of miR-34a-5p was positively correlated with DFS. Moreover, expression of miR-34a-5p was an independent prognostic factor for CRC recurrence	[185]
miR-106a	qRT-PCR	110	Downregulation of miR-106a predicted shortened DFS and OS, independent of tumor stage	[184]
miR-132	miRNA microarray, qRT-PCR	28 (testing); 151 (validation)	Low expressions were associated with poor OS and occurrence of liver metastasis	[186]
miR-150	qRT-PCR, in situ hybridization	239	High expressions were associated with longer OS. Low expressions were associated with poor therapeutic outcome in patients treated with 5-FU-based chemotherapy with or without leucovorin, levamisole or cisplatin	[91]
miR-181a	qRT-PCR	162	High expressions were correlated with poor patient prognosis. Overexpression of miR-181a repressed the expression of the tumor suppressor (PTEN) at mRNA level	[187]
miR-181b	qRT-PCR	345	High expressions were correlated with poor survival in black patients with stage II CRC	[188]
miR-188-3p	Level 3 Illumina miRNASeq data were analyzed from TCGA databasec	228	High expressions were associated with lower OS, higher tumor stage and indirectly with BRAF status	[99]
miR-195	qRT-PCR	85	Reduced expressions of miR-195 were correlated with occurrence of lymph node metastasis and advanced tumor stage	[189]
miR-199b	miRNA microarray and qRT-PCR	60	Higher level in metastatic CRC tissue compared with non-metastatic CRC tissue; low expressions were associated with longer OS	[190]
miR-203	microRNA microarray, qRT-PCR	197	High expressions were associated with more advanced TNM staging and poor survival	[90]
miR-215	qRT-PCR	34	High expressions were closely associated with poor OS	[191]
miR-218	qRT-PCR	63	High expressions were significantly associated with higher PFS, OS and response to 5-FU based chemotherapy	[192]
miR-320e	miRNA microarray and qRT-PCR	100	Elevated expressions were associated with poorer DFS and OS in stage III CRC patients	[93]
miR-429	qRT-PCR	116	High levels were correlated with OS; low levels were associated with favorable response to 5-FU-based chemotherapy	[193]
miR-494	qRT-PCR	104	High expressions were significantly associated with shorter DFS and OS. When used as a panel with 5 other miRNAs, the signature can distinguish early relapsed from non-early relapsed CRC.	[194]
miR-625-3p	qRT-PCR	94	High expressions were associated with higher OS, PFS and better response to treatment	[94]
3-miRNA signature (let-7i, miR-10b, miR-30b)	qRT-PCR	232	The addition of miR-30b to the 2-miRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II CRC who did not receive adjuvant chemotherapy	[195]
A multi-RNA-based classifier (consisting of 12 mRNAs, 1 miRNA (miR-27a) and 1 lnc RNA)	mRNA, miRNA and lncRNA data were retrieved from the TCGA data portal	663	The classifier can divide patients into high and low risk groups with significantly different OS. Moreover, the classifier is not only independent of clinical features but also with a similar prognostic ability to the well-established TNM stage	[196]

OS: Overall survival ; DFS: Disease free survival; lnc RNA: Long non-coding RNA; TCGA : The Cancer Genome Atlas Project (http://tcga-data.nci.nih.gov/).