***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: Background Alterations of PTEN , regulator of the PTEN/PI3K-AKT pathway , are common in several types of cancer . This study aim ed to do comprehensive analysis of PTEN in colorectal cancer patients . Methods Totally , 198 colorectal cancer patients who received surgery at Taipei Veterans General Hospital from 2006 to 2008 were enrolled . Mutations , loss of protein expression , promoter hypermethylation , and DNA copy number of PTEN were analyzed by sequencing , immunohistochemistry , methylation-specific polymerase chain reaction PCR , and quantitative ( QPCR ) , respectively , and correlated with clinicopathological features and patients ’ outcome . Results Genomic mutations , loss of protein expression , promoter hypermethylation , and decreased DNA copy number of PTEN were found in 4 ( 2.02 % ) , 68 ( 34.3 % ) , 54 ( 27.3 % ) , and 36 ( 18.2 % ) tumors , respectively . Of these 68 tumors with loss expression of PTEN , 34 ( 50 % ) tumors had promoter methylation and 18 ( 26.5 % ) had decreased DNA copy number . All four tumors with PTEN mutations demonstrated loss of PTEN expression . In the stage I disease , frequency of loss of PTEN expression was 20 % and significantly increased to 56.9 % in stage IV disease . Either loss expression of PTEN , PTEN hypermethylation or decreased PTEN copy number was not associated with colorectal cancer ( CRC ) patients ’ outcome . Conclusions PTEN alterations were found in up to one-third of colorectal cancers but did not impact CRC patients ’ prognosis Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems There is an increasing dem and for accurate prognostication for colorectal cancer ( CRC ) . This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients . A total of 165 CRC patients were enrolled in this prospect i ve study . Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR . Kaplan-Meier test , and univariate and multivariate Cox proportional hazards regression models were used for survival analyses . After a median follow-up of 56 months , 43 patients ( 28.7 % ) experienced tumor recurrence . In univariate survival analyses , serum methylation levels of SST and MAL were significantly predictive of cancer-specific death ( P<0.005 for both ) . The former was also a significant predictor for tumor recurrence ( P=0.007 ) . Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model ( P=0.031 and P=0.003 for cancer death and recurrence , respectively ) . When focusing on stage II and III patients , prognostication with serum methylated SST remained significant . Methylated SST detected in all serum sample s can be traced back to the matched primary tumor tissues . We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification Despite years of research and hundreds of reports on tumour markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumour marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results . The development of guidelines for the reporting of  tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . Similar to the successful CONSORT initiative for r and omised trials and the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Objective O6-methylguanine-DNA methyltransferase ( MGMT ) is a DNA repair enzyme . MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis . However , prognostic significance of MGMT alterations in colorectal cancer remains uncertain . Methods Utilizing a data base of 855 colon and rectal cancers in two prospect i ve cohort studies ( the Nurses ’ Health Study and the Health Professionals Follow-up Study ) , we detected  MGMT promoter hypermethylation in 325 tumors ( 38 % ) by MethyLight and loss of MGMT expression in 37 % ( 247/672 ) of tumors by immunohistochemistry . We assessed the CpG isl and methylator phenotype ( CIMP ) using eight methylation markers [ CACNA1 G , CDKN2A ( p16 ) , CRABP1 , IGF2 , MLH1 , NEUROG1 , RUNX3 , and SOCS1 ] , and LINE-1 ( L1 ) hypomethylation , TP53 ( p53 ) , and microsatellite instability ( MSI ) . Results  MGMT hypermethylation was not associated with colorectal cancer – specific mortality in univariate or multivariate Cox regression analysis [ adjusted hazard ratio ( HR ) = 1.03 ; 95 % confidence interval ( CI ) , 0.79–1.36 ] that adjusted for clinical and tumor features , including CIMP , MSI , and BRAF mutation . Similarly , MGMT loss was not associated with patient survival . MGMT loss was associated with G > A mutations in KRAS ( p = 0.019 ) and PIK3CA ( p = 0.0031 ) . Conclusions Despite a well-established role of MGMT aberrations in carcinogenesis , neither MGMT promoter methylation nor MGMT loss serves as a prognostic biomarker in colorectal cancer Background As screening methods for colorectal cancer ( CRC ) are limited by uptake and adherence , further options are sought . A blood test might increase both , but none has yet been tested in a screening setting . Objective We prospect ively assessed the accuracy of circulating methylated SEPT9 DNA ( mSEPT9 ) for detecting CRC in a screening population . Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma sample s before colon preparation . Using a commercially available assay , three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified r and om sample of other subjects in duplicate real time PCRs . The primary outcomes measures were st and ardised for overall sensitivity and specificity estimates . Results 7941 men ( 45 % ) and women ( 55 % ) , mean age 60 years , enrolled . Results from 53 CRC cases and from 1457 subjects without CRC yielded a st and ardised sensitivity of 48.2 % ( 95 % CI 32.4 % to 63.6 % ; crude rate 50.9 % ) ; for CRC stages I – IV , values were 35.0 % , 63.0 % , 46.0 % and 77.4 % , respectively . Specificity was 91.5 % ( 95 % CI 89.7 % to 93.1 % ; crude rate 91.4 % ) . Sensitivity for advanced adenomas was low ( 11.2 % ) . Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening . However , the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas . Clinical Trial Registration Number : Surgical excision of colorectal cancer at early clinical stages is highly effective , but 20–30 % of patients relapse . Therefore , it is of clinical relevance to identify patients at high risk for recurrence , who would benefit from adjuvant chemotherapy . The objective of this study was to identify prognostic and /or predictive methylation markers in stage II colorectal cancer patients . Therefore , we selected six gene promoters ( FZD9 , PCDH10 ( protocadherin 10 ) , SFRP2 , SPARC ( secreted protein acidic and rich in cysteine ) , UCHL1 ( ubiquitin carboxyl-terminal hydrolase 1 ) , and WIF1 ) for methylation analysis in formalin-fixed , paraffin-embedded primary tumor sample s of colorectal cancer patients ( n=143 ) who were enrolled in a prospect i ve r and omized phase III trial of the Austrian Breast and Colorectal cancer Study Group . Patients were r and omized to adjuvant chemotherapy with 5-fluorouracil and leucovorin or surveillance only .  Survival analyses revealed that combined evaluation of three promoters ( PCDH10 , SPARC , and UCHL1 ) showed differential effects with regard to disease-free survival and overall survival in the two treatment groups ( significance level 0.007 ) . In the chemotherapy arm , a statistically insignificant trend for patients without methylation toward longer survival was observed ( P=0.069 for disease-free survival and P=0.139 for overall survival ) . Contrary , patients in the surveillance arm without methylation in their gene promoters had shorter disease-free survival and overall survival ( P=0.031 for disease-free survival and P=0.003 for overall survival ) , indicating a prognostic effect of methylation in this group ( test for interaction , P=0.006 for disease-free survival and P=0.018 for overall survival ) . These results indicate that promoter methylation status of PCDH10 , SPARC , and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients and , therefore , may facilitate treatment decisions for stage II colorectal cancer BACKGROUND An accurate , noninvasive test could improve the effectiveness of colorectal-cancer screening . METHODS We compared a noninvasive , multitarget stool DNA test with a fecal immunochemical test ( FIT ) in persons at average risk for colorectal cancer . The DNA test includes quantitative molecular assays for KRAS mutations , aberrant NDRG4 and BMP3 methylation , and β-actin , plus a hemoglobin immunoassay . Results were generated with the use of a logistic-regression algorithm , with values of 183 or more considered to be positive . FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive . Tests were processed independently of colonoscopic findings . RESULTS Of the 9989 participants who could be evaluated , 65 ( 0.7 % ) had colorectal cancer and 757 ( 7.6 % ) had advanced precancerous lesions ( advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension ) on colonoscopy .  The sensitivity for detecting colorectal cancer was 92.3 % with DNA testing and 73.8 % with FIT ( P=0.002 ) . The sensitivity for detecting advanced precancerous lesions was 42.4 % with DNA testing and 23.8 % with FIT ( P<0.001 ) . The rate of detection of polyps with high- grade dysplasia was 69.2 % with DNA testing and 46.2 % with FIT ( P=0.004 ) ; the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4 % and 5.1 % , respectively 
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Conclusion This systematic review reflects that adequate reporting according to REMARK and validation of prognostic methylation markers is absent in the majority of CRC methylation marker studies .