***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Prognosis of patients with colorectal cancer ( CRC ) is generally poor because of the lack of simple , convenient , and noninvasive tools for CRC detection at the early stage . The discovery of microRNAs ( miRNAs ) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis . We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC . We also studied its possible role in monitoring the progression of CRC . We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis . Using quantitative reverse transcription polymerase chain reactions , we tested ten c and i date miRNAs in a training set ( 30 CRCs vs 30 controls ) . Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system . Other independent sample s , including 83 CRCs and 59 controls , were used to vali date the diagnostic model . In the training set , six serum miRNAs ( miR-21 , let-7 g , miR-31 , miR-92a , miR-181b , and miR-203 ) had significantly different expression levels between the CRCs and healthy controls . Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC sample s from cancer-free controls . The areas under the receiver operating characteristic ( ROC ) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum sample s , respectively . However , for the same serum sample s , the areas under the ROC curve used by the tumor markers carcinoembryonic antigen ( CEA ) and carbohydrate antigen 19 - 9 ( CA19 - 9 ) were only 0.649 and 0.598 , respectively . The expression levels of the six serum miRNAs were also correlated with CRC progression . Thus , the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC , with relatively high sensitivity and specificity Objective The detection of  molecular markers  in stool sample s is a potential strategy for colorectal cancer ( CRC ) screening . This study evaluated the feasibility of detecting miR-21 and miR-92a in stool sample s of patients with CRC or polyps . Methods The reproducibility of detection and stability of stool-based microRNA were evaluated . Stool sample s were collected from 88 patients with CRC , 57 patients with colorectal polyps and 101 healthy controls .  MiRNA levels in CRC tissues and stool sample s were detected by real-time quantitative reverse transcription PCR .  Stool miR-21 and miR-92a levels were compared before and after the removal of tumour or advanced adenoma . Results The study demonstrated that stool-based miRNA were stable with highly reproducible detection . The expression of miR-21 and miR-92a was significantly higher in CRC tissues compared with their adjacent normal tissues ( p<0.0001 ) . Patients with CRC had a significantly higher stool miR-21 level ( p<0.01 ) and miR-92a level ( p<0.0001 ) compared with normal controls . Stool miR-92a , but not miR-21 , was significantly higher in patients with polyps than in controls ( p<0.0001 ) . At a cut-off value of 435 copies/ng of stool RNA , miR-92a had a sensitivity of 71.6 % and 56.1 % for CRC and polyp , respectively , and a specificity of 73.3 % . In addition , the stool miR-92a level demonstrated a higher sensitivity for distal CRC than proximal CRC ( p<0.05 ) , and a higher sensitivity for advanced adenoma than minor polyps ( p<0.05 ) . Removal of tumour result ed in reduced stool miR-21 and miR-92a levels ( p<0.01 ) , and the removal of advanced adenoma result ed in a reduction of the stool miR-92a level ( p<0.05 ) . Conclusion Stool miRNA are useful for screening CRC and polyps To reduce the colorectal cancer ( CRC ) mortality rate , we have reported several CRC screening methods using colonocytes isolated from feces . Expression analysis of oncogenic microRNA ( miRNA ) in peripheral blood was recently reported for CRC detection . In the present study , we conducted miRNA expression analysis of exfoliated colonocytes isolated from feces for CRC screening . Two hundred six CRC patients and 134 healthy volunteers were enrolled in the study .  miRNA expression of the miR-17 - 92 cluster , miR-21 , and miR-135 in colonocytes isolated from feces as well as frozen tissues was analyzed by quantitative real-time PCR . The expression of the miR-17 - 92 cluster , miR-21 , and miR-135 was significantly higher in CRC tissues compared with normal tissues . The exfoliated colonocytes of 197 CRC patients and 119 healthy volunteers were analyzed because of the presence of sufficient miRNA concentration . miR-21 expression did not differ significantly between CRC patients and healthy volunteers ( P = 0.6 ) . The expression of miR-17 - 92 cluster and miR-135 was significantly higher in CRC patients than in healthy volunteers ( P < 0.0001 ) . The overall sensitivity and specificity by using miRNA expression was 74.1 % ( 146/197 ; 95 % confidence interval , 67.4 - 80.1 ) and 79.0 % ( 94/119 ; 95 % confidence interval , 70.6 - 85.9 ) , respectively . Sensitivity was dependent only on tumor location ( P = 0.0001 ) . miRNA was relatively well conserved in exfoliated colonocytes from feces both of CRC patients and healthy volunteers .  miRNA expression analysis of the isolated colonocytes may be a useful method for CRC screening . Furthermore , oncogenic miRNA highly expressed in CRC should be investigated for CRC screening tests in the future . Cancer Prev Res ; 3(11 ) ; 1435–42 . © 2010 AACR In patients with colorectal cancer , circulating micro RNA-21 ( miR-21 ) is overexpressed and may act as a potential diagnostic and prognostic biomarker . In the present study , serum miR-21 level was determined in patients with colorectal cancer and control subjects in an attempt to explore its potential clinical diagnostic and prognostic value .  Serum levels of miR–21  were measured in 40 patients with colorectal adenocarcinoma and 40 control subjects using a quantitative reverse-transcriptase polymerase chain reaction ( qRT-PCR ) assay .  Serum miR-21 levels were compared in the colorectal cancer patients and control subjects . Furthermore , the association between serum miR-21 level and the clinical stages of tumors was also examined in the patients . Serum miR-21 level was significantly elevated in colorectal adenocarcinoma patients relative to control subjects ( P = 0.0001 ) , and it was revealed as a potential diagnostic biomarker for differentiating the patients from control subjects . Increased levels of serum miR-21 were associated with clinical stages of tumors in the patients ( P = 0.01 ) . These results indicated that serum miR-21 levels could serve as a reliable diagnostic and prognostic biomarker for colorectal adenocarcinoma BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects RATIONALE Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis , the assessment of infection in critically ill patients is often a challenge for clinicians . In this setting , simple biomarkers , especially when used in combination , could prove useful . OBJECTIVES To determine the usefulness of combination biomarkers to diagnose sepsis . METHODS Three hundred consecutive patients were enrolled to construct a biologic score that was next vali date d in an independent prospect i ve cohort of 79 critically ill patients from another center . MEASUREMENT AND MAIN RESULTS Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 ( sTREM-1 ) and procalcitonin ( PCT )  were assayed , and the expression of the high-affinity immunoglobulin-Fc fragment receptor I ( FcγRI ) CD64 on neutrophils ( polymorphonuclear [ PMN ] CD64 index ) in flow cytometry was measured . A " bioscore " combining these biomarkers was constructed . Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others ( P < 0.001 for the three markers ) . These biomarkers were all independent predictors of infection , the best receiver-operating characteristic curve being obtained for the PMN CD64 index . The performance of the bioscore , better than that of each individual biomarker , was externally confirmed in the validation cohort . CONCLUSIONS This prospect i ve study , including inceptive and validation cohorts of unselected intensive care unit patients , demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient 
    Output:
    
Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker , while tissue miR-21 could be a prognostic marker for colorectal cancer .
In addition , miRNA combination biomarkers may provide a new approach for clinical application