Zhang H, Zhu YQ, Qi J, Wang QX, Cai SS, Zhu SY, Zhu XW, Wang XT. Accuracy of early detection of colorectal tumours using stool methylation markers: A meta-analysis. World J Meta-Anal 2013; 1(3): 147-156 [DOI: 10.13105/wjma.v1.i3.147]
Corresponding Author of This Article
Dr. Jian Qi, Department of Gastroenterology and Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, 169 Wuchang Donghu Lu, Wuhan 430071, Hubei Province, China. qiqidelizi@aliyun.com
Research Domain of This Article
Oncology
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hu Zhang, You-Qing Zhu, Jian Qi, Qi-Xian Wang, Sha-Sha Cai, Si-Ying Zhu, Xiao-Wen Zhu, Xin-Tao Wang, Department of Gastroenterology and Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
ORCID number: $[AuthorORCIDs]
Author contributions: Qi J and Zhu YQ designed this study and critically revised the article; Zhang H and Qi J were responsible for data acquisition and extracted the data; Zhang H drafted the manuscript, analyzed the data and interpreted the results; Wang QX, Cai SS, Zhu SY, Zhu XW and Wang XT were involved in editing the manuscript; all authors read and approved the final manuscript to be published.
Supported by The National Natural Science Foundation of China Youth Science Fund, No. 81101868; The Natural Science Foundation of Hubei Province of China, No. 2011CDB505
Correspondence to: Dr. Jian Qi, Department of Gastroenterology and Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, 169 Wuchang Donghu Lu, Wuhan 430071, Hubei Province, China. qiqidelizi@aliyun.com
Telephone: +86-27-87336141 Fax: +86-27-87336141
Received: July 9, 2013 Revised: October 21, 2013 Accepted: November 2, 2013 Published online: November 26, 2013 Processing time: 162 Days and 22.4 Hours
Abstract
AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours.
METHODS: Electronic databases including PubMed, Web of Science, Chinese Journal Full Text Database and Wanfang Journals Full-text Database were searched to find relevant original articles about methylated genes used in diagnosing colorectal tumours. Quality assessment of diagnostic accuracy studies items were used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis.
RESULTS: Thirty-four articles met the inclusion criteria, and 4151 patients were included. Pooled diagnostic performances of SFRP2 methylation for colorectal cancer (CRC) provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic odds ratio (DOR) was 47.57 (95%CI: 20.08-112.72), and the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: the sensitivity was 43% (95%CI: 38%-49%), the specificity was 94% (95%CI: 91%-97%), the DOR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563.
CONCLUSION: Stool-based DNA testing may be useful for non-invasively diagnosing colorectal tumours, and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis.
Core tip: The analysis of stool methylation markers as a non-invasive test is important for the early diagnosis of colorectal tumours. However, no consensus has been reached with regard to the role of stool methylation markers in colorectal tumour diagnosis. We performed a meta-analysis of 34 articles, and the pooled results showed that stool methylation markers could be used as a valuable diagnostic and predictive tool for colorectal tumours and SFRP2 methylation serves as a promising marker with great potential in early colorectal cancer diagnosis.
Citation: Zhang H, Zhu YQ, Qi J, Wang QX, Cai SS, Zhu SY, Zhu XW, Wang XT. Accuracy of early detection of colorectal tumours using stool methylation markers: A meta-analysis. World J Meta-Anal 2013; 1(3): 147-156
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in Western countries[1,2]. The 5-year survival of stage I CRC has reached 90%[3], but less than 10% of CRC cases have distant metastases[4]. However, most cases of CRC are diagnosed at the middle or late stage because no typical symptoms for early-stage CRC exist[5]. Therefore, the diagnosis of CRC at early stages has great importance for reducing CRC mortality.
Early diagnosis of CRC will help reduce mortality and the costs for surgery. The current colonoscopy screening test is of high efficacy, but the acceptability of this procedure in the general public is rather low. As an available non-invasive method, faecal testing has a unique advantage when compared to other screening modalities. Although faecal occult blood testing (FOBT) has been confirmed to reduce mortality due to CRC, the test has little or no impact on the incidence of CRC because of its low-level sensitivity for the detection of adenoma[6], i.e., a sensitivity of only 10%-20%[7]. Compared to FOBT, the most important advantage of methylation markers in stool samples is their higher accuracy and sensitivity for the diagnosis of premalignant lesions of CRC[8].
DNA methylation often occurs in the early stage of CRC, and many studies have been performed on the diagnosis of colorectal tumours by determining the methylation of genes in stool samples. However, the results of these studies are variable although inspiring. Thus, this meta-analysis was conducted to assess the accuracy of the detection of colorectal tumours using methylation markers in stool samples.
MATERIALS AND METHODS
Search strategy
A literature search was performed independently by two investigators (Zhang H and Qi J) using the following databases: PubMed, Web of Science, Chinese Journal Full Text Database and Wanfang Journals Full-text Database. All references that were cited in these studies and all published reviews were also searched. All English and Chinese references for analyses were published before January 2013. The following keywords were used in the search strategy: “colon/rectal/colorectal”, “cancer/tumours”, “stool,” and “methylation”. In this meta-analysis, 2 × 2 tables were constructed from each study for the true-positive, false-negative, true-negative and false-positive values.
Inclusion and exclusion criteria
Eligible studies were required to meet all of the following criteria: (1) the data were independent; (2) CRC was diagnosed by analyzing DNA methylation in stool sample; (3) patients were diagnosed with colorectal cancer or colorectal adenomas by pathology; and (4) the colonoscopy result of control individuals was normal.
Exclusion criteria for this meta-analysis were as follows: (1) studies on secondary CRC or primary CRC with distant metastases and (2) studies on CRC patients receiving chemotherapy or curative surgery.
Data extraction and quality assessment
The following data were extracted from each study: author, year of publication, country or region, sample size, the name of genes, the detection method of methylation and the study design. The data were independently extracted by two investigators (Zhang H and Qi J), and discrepancies were solved by a third investigator (Zhu YQ) and collective discussion. Quality Assessment of studies of Diagnostic Accuracy[9] (QUADAS) was used to assess the quality of the primary studies with diagnostic accuracy, and quality scoring was appraised based on the empirical evidence, the experts’ opinions and the formal consensus. Score of 1, 0 or -1 was given to the articles that were in compliance with the standards completely, unclear or out of standards, respectively, and the full score was 14.
Statistical analysis
All statistics were calculated and then combined using a random-effects model and 95%CI as effect measurements. The diagnostic odds ratio (DOR) reflects the relationship between the result of the diagnostic test and the disease. The summary receiver operation characteristic (SROC) curve displays the trade-off between sensitivity and specificity and represents a global summary of test performance. We used the Q-value, which is the intersection point of the SROC curve with a diagonal line from the left upper corner to the right lower corner of the receiver operation characteristic (ROC) space, which corresponds to the highest value of sensitivity and specificity for the test. The positive likelihood ratio (PLR) represents the value by which the odds of the disease increase when a test is positive, whereas the negative likelihood ratio (NLR) shows the value by which the odds of the disease decrease when a test is negative. Statistical heterogeneity was assessed using the Chi-square test, and alpha significance testing was performed at the two-tailed 0.05 level. The professional statistical software programs (Meta-DiSc 1.4 and SPSS 13.0) were used for analysis. Publication bias was assessed by Egger analysis.
RESULTS
The literature search retrieved 453 citations, of which 344 were excluded because they were duplicates. Of the 109 potentially eligible studies, 75 publications were excluded because they did not investigate colorectal tumour studies (n = 6), included no diagnostic value studies (n = 15), were reviews (n = 26) or had overlapping data (n = 28). Finally, 34 studies that focused on the target patient spectrum were included (Figure 1).
Of the 34 studies, 7 were Chinese and 27 were English, and they included 4151 patients (Table 1). These studies were performed in 10 countries or regions (including China, the United States, the Netherlands, Spain, Japan, Germany, Iran, Hong Kong, Austria and South Korea). In these studies, 31 evaluated CRC, and 26 evaluated colorectal adenoma. Twenty-two studies focused on the methylation of a single gene, and the other 12 studies involved the methylation of multiple genes.
Table 1 The characteristics of the included studies in the meta-analysis and QUADAS scores.
Genes evaluated in these studies are mainly involved in three types of regulation pathways: the Wnt pathway, the DNA damage repair pathway and other pathways. Four genes of the Wnt pathway were involved in 10 studies: secreted frizzled-related proteins (SFRP1, SFRP2, SFRP5) and adenomatous polyposis coli (APC). Two genes of the DNA damage repair pathway were involved in 7 studies: O-6-methylguanine-DNA methyltransferase (MGMT) and Mut L homologue 1 (MLH1). Twenty-seven studies involved 16 genes of other pathways: vimentin, oncostain M receptor-β (OSMR), phosphatase and actin regulator 3 (PHACTR3), cyclin-dependent kinase inhibitor 2A (CDKN2A), tissue factor pathway inhibitor 2 (TFPI2), hyperplastic polyposis protein gene (HPP1), GATA4, human lactoferrin (HLTF), ATM, ras association domain family 2 (RASSF2), RARB2, hypermethylated in cancer 1 (HIC), engrailed gene (EN1), N-myc downstream-regulated gene family (NDRG4), IGTA4 and T-cell differentiation protein (MAL).
Qualitative and quantitative methods were the two main types of methods used for methylation detection. The qualitative method included methylation-specific PCR (MSP) and methylation-specific melting curve analysis (MS-MCA). The quantitative method included Methl-BEAMing; quantitative MSP (qMSP); MethyLight; combined bisulfite restriction analysis (COBRA); and quantitative, allele-specific, real-time target and signal amplification (QuARTS).
Colorectal carcinoma meta-analysis
The colorectal carcinoma results were pooled from 31 studies and are shown in Table 2. The meta-analysis showed that the sensitivity and specificity of gene methylation for the detection of colorectal carcinoma were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. The PLR was 7.94 (95%CI: 6.08-10.36), the NLR was 0.31 (95%CI: 0.25-0.39), the DOR was 30.86 (95%CI: 22.33-42.66), and the symmetric area under the curve was 0.9286.
Table 2 Methylation of pooled genes for the diagnosis of colorectal cancer.
Wnt pathway
DNA damage repair pathway
Other pathways
SE (95%CI)
SP (95%CI)
DOR (95%CI)
AUC
Wnt pathway
DNA damage repair pathway
Other pathways
73% (0.71-0.75)
92% (90%-93%)
30.86 (22.33-42.66)
0.929
Wnt pathway
-
-
74% (70%-77%)
93% (90%-95%)
33.92 (17.73-64.90)
0.932
-
DNA damage repair pathway
-
42% (36%-47%)
97% (94%-99%)
12.87 (5.98-27.72)
0.730
-
-
Other pathways
57% (55%-60%)
94% (93%-95%)
20.93 (15.56-28.15)
0.921
SFRP2
-
-
79% (75%-82%)
93% (90%-96%)
47.57 (20.08-112.72)
0.957
-
MGMT
-
47% (40%-53%)
95% (90%-98%)
11.67 (5.10-26.67)
0.709
-
MLH
-
28% (18%-39%)
100% (95%-100%)
23.68 (3.02-185.44)
0.500
-
-
Vimentin
48% (42%-54%)
93% (90%-95%)
14.95 (8.99-24.84)
0.862
-
-
OSMR
47% (40%-54%)
95% (91%-98%)
14.66 (5.06-42.47)
0.225
-
-
P16
50% (42%-58%)
98% (92%-100%)
24.39 (7.26-81.96)
0.975
SFRP2
MGMT
-
69% (66%-72%)
94% (91%-96%)
33.24 (16.76-65.93)
0.946
SFRP2
MLH
-
72% (68%-75%)
94% (92%-96%)
43.03 (20.15-91.87)
0.953
SFRP2
MLH
Vimentin
64% (61%-67%)
94% (92%-95%)
27.11 (16.48-44.61)
0.934
SFRP2
MLH
OSMR
65% (62%-69%)
95% (93%-96%)
33.10 (17.12-63.98)
0.951
SFRP2
MLH
P16
68% (64%-71%)
95% (93%-97%)
38.86 (20.11-67.54)
0.952
Heterogeneity was significant for the sensitivity (P < 0.001), specificity (P = 0.0012), PLR (P = 0.0023), NLR (P < 0.001), and DOR (P = 0.0245).
Of the involved regulation mechanisms, we found that DOR and AUC of the methylated genes belonging to the Wnt pathway were higher than the genes of the DNA damage repair pathway and other pathways. The sensitivity, specificity, DOR and AUC of different methylated genes in the three types of pathways were calculated (Table 2), and the results indicated that the accuracy of faecal SFRP2 methylation in the diagnosis of colorectal carcinoma was higher than that of other genes, with a sensitivity of 79% (95%CI: 75%-82%) (Figure 2A), a specificity of 93% (95%CI: 90%-96%) (Figure 2B), a DOR of 47.57 (95%CI: 20.08-112.72), and the area under the curve of 0.9565 (Figure 2C).
Figure 2 Forest plot of SFRP2 methylation in the diagnosis of colorectal cancer.
A: The sensitivity of SFRP2 methylation in stool samples used for colorectal carcinoma diagnosis. The point estimates of specificity from each study are shown as red squares; B: The specificity of SFRP2 methylation in stool samples used for colorectal cancer diagnosis. The point estimates of specificity from each study are shown as blue squares; C: The summary receiver operating characteristic curves of SFRP2 methylation assays used for diagnosis of colorectal carcinoma. Red circles represent each study that was included in the meta-analysis. The size of each study is indicated by the size of the red circle. Summary receiver operating characteristic curves summarize the overall diagnostic accuracy. Error bars indicate the 95%CI, and df indicates the degrees of freedom.
Colorectal adenoma meta-analysis
Pooled colorectal adenoma analysis (Table 3), including 26 studies, provided the following results: the sensitivity and specificity of gene methylation for colorectal adenoma diagnosis were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. The PLR was 5.52 (95%CI: 4.23-7.19), the NLR was 0.52 (95%CI: 0.44-0.61), and the DOR and symmetric area under the curve were 12.61 (95%CI: 8.66-18.37) and 0.8830, respectively.
Table 3 Methylation of pooled genes for the diagnosis of colorectal adenomas.
Wnt pathway
DNA damage repair pathway
Other pathways
SE (95%CI)
SP (95%CI)
DOR (95%CI)
AUC
Wnt pathway
DNA damage repair pathway
Other pathways
51% (47%-54%)
92% (90%-93%)
12.61 (8.66-18.37)
0.883
Wnt pathway
-
-
40% (35%-46%)
95% (92%-97%)
10.81 (6.43-18.16)
0.932
-
DNA damage repair pathway
-
21% (17%-27%)
95% (91%-97%)
4.23 (2.01-8.88)
0.672
-
-
Other pathways
32% (28%-35%)
94% (93%-95%)
7.78 (5.48-11.05)
0.873
SFRP2
-
-
43% (38%-49%)
94% (91%-97%)
11.06 (5.77-21.18)
0.956
-
MGMT
-
29% (22%-36%)
93% (87%-96%)
4.42 (2.18-8.95)
0.614
-
MLH
-
8% (4%-16%)
98% (92%-100%)
2.35 (0.14-40.83)
-
-
-
Vimentin
23% (17%-31%)
95% (92%-98%)
8.30 (2.60-26.55)
0.898
-
-
OSMR
25% (14%-39%)
95% (91%-98%)
5.20 (1.44-18.82)
0.817
-
-
P16
33% (23%-44%)
97% (89%-100%)
13.27 (3.40-51.83)
0.97
SFRP2
MLH
-
34% (29%-39%)
95% (92%-97%)
9.62 (4.64-19.93)
0.947
SFRP2
MGMT
-
38% (33%-42%)
94% (91%-96%)
7.85 (4.79-12.87)
0.753
SFRP2
-
OSMR
41% (35%-46%)
95% (92%-96%)
9.25 (5.13-16.69)
0.948
SFRP2
-
Vimentin
36% (32%-41%)
95% (93%-96%)
9.88 (5.55-17.57)
0.946
SFRP2
-
P16
41% (36%-46%)
95% (92%-97%)
10.37 (6.21-17.31)
0.948
SFRP2
MGMT
Vimentin
34% (30%-38%)
94% (92%-96%)
7.81 (4.96-12.29)
0.804
SFRP2
MGMT
OSMR
36% (32%-41%)
94% (92%-96%)
7.25 (4.61-11.39)
0.775
SFRP2
MGMT
P16
37% (33%-41%)
94% (92%-96%)
7.92 (5.14-12.21)
0.772
SFRP2
MLH
Vimentin
31% (27%-35%)
95% (93%-97%)
8.99 (4.95-16.31)
0.944
SFRP2
MLH
OSMR
33% (29%-38%)
95% (93%-97%)
8.37 (4.50-15.59)
0.941
SFRP2
MLH
P16
34% (30%-38%)
95% (93%-97%)
9.98 (5.45-18.27)
0.947
Heterogeneity was also significant regarding sensitivity (P < 0.001), specificity (P = 0.0233), PLR (P = 0.1166), NLR (P < 0.001), and DOR (P = 0.0565).
The DOR and AUC of the methylated Wnt pathway genes were higher than those of the genes of the DNA damage repair pathway and other pathways when grouping all of the genes by pathway for analysis. In these regulation mechanisms, we also found that the sensitivity and specificity of the methylated genes in the Wnt pathway were higher than those in the DNA damage repair pathway and the other pathway. The sensitivity, specificity, DOR and AUC of the different methylated genes in the three types of pathways were calculated (Table 3), and the results indicated that the values of DOR and AUC of P16 and SFRP2 were higher than those of other genes, but the accuracy of faecal SFRP2 methylation for the diagnosis of colorectal adenoma was higher than that of P16 methylation according to sensitivity (Figure 3).
Figure 3 Forest plot of SFRP2 methylation in the diagnosis of colorectal adenomas.
A: Plot and table of the sensitivity of SFRP2 for diagnosis of colorectal adenomas; B: Plot and table of the specificity of SFRP2 for diagnosis of colorectal adenomas; C: The symmetric summary receiver-operating characteristic of SFRP2 for diagnosis of colorectal adenomas.
Meta-regression
In the meta-regression analysis, the difference in relative diagnostic odds ratio (RDOR) values between the higher and lower quality studies was not significant. We also noted that the differences between the blinded and non-blinded methods, qualitative and quantitative methods, single- and multiple-gene methylation did not reach statistical significance, indicating that these potential factors did not substantially affect the diagnostic accuracy, as shown in Table 4.
Table 4 Weighted meta-regression on the diagnostic accuracy of the gene methylation assays.
In our meta-analysis, publication bias was evaluated using the Egger test. The results showed no significant publication bias among the studies of SFRP2 methylation in faecal samples from CRC or adenoma patients (Figure 4).
Figure 4 Assessment of the publication bias in the faecal SFPR2 methylation for the diagnosis of colorectal cancer (A) and adenomas (B).
No significant publication biases were found in any of these studies (all P > 0.05).
DISCUSSION
It is widely accepted that DNA methylation in stool samples may be valuable for increasing the rate of CRC detection at earlier stage[44]. In the present study, we focused on the detection performance of gene methylation in stool samples for patients with colorectal tumours. Our analysis suggests that the specificity of SFRP2 methylation is high (93% for CRC and 94% for colorectal adenoma) for the detection of colorectal tumours; however, it has moderate (79%) and low sensitivity (43%) for diagnosing CRC and adenoma, respectively. Compared to FOBT, with a sensitivity of 14% for colorectal tumour diagnosis[45], the detection accuracy of faecal methylation biomarkers was higher as a CRC screening method.
The DOR is an indicator of test accuracy. The value of the DOR ranges from 0 to infinity, and higher values indicate better discriminatory test performance. In this meta-analysis, we found that the DOR of faecal SFRP2 methylation for colorectal carcinoma and adenoma were 47.57 and 11.06, respectively, which indicated a high level of overall accuracy for CRC and a low level for adenoma. The SROC curve represents an overall measure of the discriminatory power of a test. The area under the curve of 1 for any test indicates that the test is excellent. Our data showed that the area under the curve (AUC) of the SROC curve for faecal SFRP2 methylation for the diagnosis of colorectal carcinoma and adenoma were 0.9565 and 0.9563, respectively, which indicated that faecal SFRP2 methylation is an excellent diagnostic biomarker for colorectal tumours.
Because the DOR and SROC curve are not easy to use in clinical practice, the likelihood ratios are considered to be more clinically meaningful. For a high-quality diagnostic test, a PLR of > 10 or an NLR < 0.1 is typically required. However, our meta-analysis showed that neither PLR nor NLR alone was adequate to confirm or exclude the diagnosis of colorectal carcinoma or adenoma. The PLR value was 9.12 in the diagnosis analysis of CRC, which suggested that patients with a positive faecal SFRP2 methylation assay had a nine-fold chance of being diagnosed with CRC than non-CRC. Therefore, a colonoscopy was necessary for patients with a positive faecal SFRP2 methylation assay to confirm the diagnosis of CRC with high probability. On the other hand, an NLR of 0.24 in the diagnosis analysis of CRC suggested that if a faecal SFRP2 methylation assay result was negative, the probability rate of the individual having CRC was 24%. For the diagnosis of colorectal adenoma, a PLR of 5.99 suggested a moderate necessity to consider colonoscopy for patients with a positive faecal SFRP2 methylation assay to confirm the diagnosis of colorectal adenoma. Moreover, the NLR was 0.60 in the diagnosis analysis of colorectal adenoma. These data suggest that a negative faecal SFRP2 methylation assay result should not be used alone as a justification for denying or discontinuing the screening of colorectal adenomas.
An aberrant Wnt signalling pathway is an early event in 90% of colorectal carcinomas. SFRPs are secreted glycoproteins that antagonise Wnt signaling via different direct or indirect mechanisms. Thus, the role of SFRPs as a negative regulator of Wnt signaling may have important significance in tumourigenesis. These epigenetic events are involved in early steps of colon carcinogenesis, and changes in the status of DNA methylation are associated with early steps of the histologic progression of colon carcinoma. Our previous studies of CRC tissue showed that SFRP1 and SFRP2 were methylated in more than 80.6% of colorectal carcinomas[46]. Therefore, faecal SFRP2 methylation could be expected to be a biomarker for the screening of colorectal tumours. Although it cannot be generally used as a screening tool for the financial limited, the analysis of methylation markers offers a variety of new opportunities for developing biomarkers for colorectal tumours at the molecular level.
Our meta-analysis had several limitations. First, none of the included studies were multicentre or large-blinded, randomized, controlled trials. Second, conference abstracts and non-English and non-Chinese language studies were excluded, which might have led to publication bias. Third, studies on DNA methylation with statistical significance tend to be published and cited. Finally, due to the absence of case-mix difference analysis, smaller trials may show larger treatment effects than larger studies (e.g., patients with only localised vs metastatic disease).
To sum up, stool-based DNA methylation has been shown to be highly discriminatory in the detection of colorectal tumours. Our results demonstrate that SFRP2 methylation, as a non-invasive modality, shows promise for the accurate detection of CRC; however, a large number of studies are required to further confirm the role of faecal SFRP2 methylation for the early and accurate CRC diagnosis.
COMMENTS
Background
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in Western countries. The diagnosis of CRC at early stages has great importance for reducing CRC mortality. Although significant advances have been achieved in diagnostic technologies, the current available modalities for diagnosing CRC remain suboptimal.
Research frontiers
DNA methylation often occurs during the early stages of colon tumours and has played an important role in oncology, especially in the early diagnosis of colorectal tumours. However, no consensus with regard to the role of stool methylation markers in colon tumours exists.
Innovations and breakthroughs
Stool methylation markers as an available non-invasive modality have high accuracy and sensitivity for the diagnosis of premalignant lesions of CRC. A few systematic reviews about the efficacy of stool methylation markers in colorectal tumour diagnosis exist. This article comprehensively assesses the accuracy of methylated genes in stool samples for diagnosing colorectal tumours.
Applications
Analysis of DNA methylation in stool samples may be used as a non-invasive test for the diagnosis of CRC, and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis.
Terminology
Diagnostic odds ratio (DOR) reflects the relationship between the result of the diagnostic test and the disease. The summary receiver operation characteristic (SROC) curve displays the trade-off between sensitivity and specificity and represents a global summary of test performance. We used the Q-value, the intersection point of the SROC curve with a diagonal line from the left upper corner to the right lower corner of the receiver operation characteristic (ROC) space, which corresponds to the highest value of sensitivity and specificity for the test. The positive likelihood ratio (PLR) represents the value by which the odds of the disease increase when a test is positive, whereas negative likelihood ratio (NLR) shows the value by which the odds of the disease decrease when a test is negative.
Peer review
This study reviewed 34 trials to evaluate the accuracy of stool methylation genes for diagnosing colorectal tumours. Based on these analyses, the authors conclude that stool SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis. The analysis was carefully performed, the results were clearly presented and summarized, and valuable advice for early clinical diagnosis of colorectal tumours was provided.
Footnotes
P- Reviewers: Meshikhes AWN, Xia HHX S- Editor: Cui XM L- Editor: Wang TQ E- Editor: Lu YJ
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