MicroRNA-21 as a potential colon and rectal cancer biomarker

Table 1 Current screening methods and guidelines for colorectal cancer

Method	Sensitivity	Interval	Society
Fecal tests
FOBT		Yearly	USPSTF, ASGE,
			USMSTF
FIT	65.8%[32,33]	Yearly
Fecal DNA	50%-60%[34]	Unspecified	USMSTF
Serum markers
CEA	30%[35]
CA19-9
Imaging tests
DCBE	85%-97%[36]	Every 5 years	USMSTF
CTC	55%-94%[37]	Every 5 years	USMSTF
Optical tests
FS		Every 5 years	USPSTF, ASGE, USMSTF
		Every 10 years
FC			USPSTF, ASGE, USMSTF

FOBT: Fecal occult blood test; FIT: Fecal immunochemical based stool tests; CEA: Carcinoembryonic antigen; DCBE: Double-contrast barium enema; CTC: Computed tomography colonography; FS: Flexible sigmoidoscopy; FC: Flexible colonoscopy; USPSTF: United States Preventive Services Task Force; ASGE: American Society for Gastrointestinal Endoscopy; USMSTF: Multi-Society Task Force on Colorectal Cancer.

Table 2 MicroRNA-21 expression in colorectal cancer

Ref.	Regulation	Biological material tested	Detection method	Clinical relevance	Comment
Tumor development
Fassan et al[60]	Up	300 polypoid lesions of the colon mucosa	RT-PCRISH	Significant miR-21 upregulation in preneoplastic/neoplastic samples	High miR-21 expression is consistent with PDCD4 downregulation
Yantiss et al[61]	Up	24 patients < 40 years45 patients ≥ 40 years	RT-PCR	Significantly higher expression
Tumor diagnosis
Link et al[62]	Up	Stool samples	RT-PCR	Higher expression in patients with adenomas and CRCs	May be an excellent candidate of a noninvasive screening test for colorectal neoplasms
Tumor prognosis
Chang et al[63]	Up	48 colorectal tumors, 61 normal tissues , 7 polyps	RT-PCR	Disease recurrence	miR-21 post-transcriptionallymodulates PDCD4 via mRNA degradation
Nielsen et al[47]	Up	130 stage II colon and 67 stage II rectal cancer specimens	ISH	Shorter disease-free survival in colon cancer, but not in rectal cancer
Kulda et al[64]	Up	46 paired tissue samples30 tissue samples with live metastasis	RT-PCR	Disease-free interval
Schetter et al[46]	Up	196 paired tissues	RT-PCR	Association with cancer-specific mortality, including stage II patients alone	miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients
Schetter et al[46]	Up	US cohort: 84 patients; Hong Kong cohort: 113 patients	MicroRNA microarray, RT-PCR	Poor survival and poor therapeutic outcome

RT-PCR: Reverse transcription-polymerase chain reaction; ISH: In situ hybridization; PDCD4: Programmed cell death protein 4.