Identification of stress‐related microRNA biomarkers in type 2 diabetes mellitus: A systematic review and meta‐analysis
Authors: Jia-Jiang-Hui Li
Yan He
Yu-Xiang Yan
Ying-Zhi Liang
Ling Zhang
Huan-Bo Xiao
Journal: Journal of Diabetes (2020)
Discipline: CLINICAL MEDICINE
Keywords: 2型糖尿病; meta-analysis; meta分析; miRNA; microRNA
Affiliations: Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China., Municipal Key Laboratory of Clinical Epidemiology, Beijing, China., Department of Preventive Medicine, Yanjing Medical College, Capital Medical University, Beijing, China.

Abstract:  Background: Many studies have investigated microRNAs (miRNAs) in the detection of type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress-related miRNAs used as biomarkers of T2DM are summarized and analyzed. Methods: PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for case-control miRNA profiling studies about T2DM. A meta-analysis under a random effect was performed. Subgroup analysis was conducted based on different tissues and species. Sensitivity analysis was conducted to confirm the robustness among studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence intervals (95% CIs), and P-values. Results: The present meta-analysis included 39 case-control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in three or more studies and, of these, 18 were inconsistent in their direction of dysregulation. Two significantly dysregulated miRNAs (let-7 g and miR-155) were identified in the meta-analysis. Four miRNAs (miR-142-3p, miR-155, miR-21, and miR-34c-5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR-146a, miR-199a-3p, miR-200b, miR-29b and miR-30e) were dysregulated in animal models of diabetes. In addition, two dysregulated miRNAs (miR-146a and miR-21) were highly cornea specific and heart specific. In sensitivity analysis, only miR-155 was still significantly dysregulated after removing studies with small sample sizes. Conclusions: The present meta-analysis revealed that 16 stress-related miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR-19a, miR-26b and miR-27b were selected as potential circulating biomarkers of T2DM. In addition, miR-146a and miR-21 were identified as potential tissue biomarkers of T2DM. 

Retracted: No

PubPeer comments:
 We found that this article plagiarized our original paper [DOI:10.1007 s00125-015-3510-2] published in ***Diabetologia*** *2015*. Our findings of this plagiarism case were submitted to the Editors-in-Chief of the Journal of Diabetes (JD) on 23 May 2018. We were delighted to receive JD s handling editor positive reply u2013 they will retract the JD paper u2013 and soon later on 11 Jun 2018 we received an apology email message (in Chinese language) from the corresponding author of the JD paper, offering us a co-authorship to settle this case. It seemed to us that the corresponding author was seeking all means to settle this case but would not retract the paper. We did not respond because such co-authorship does not comply with the authorship ethics set forth by ICMJE, COPE, .... While we had been waiting for the paper retraction to happen, suddenly we were shocked by a message received on 30 Jul 2018 from the publisher s regional office (located in the same city of the authorsu2019 institution), alleging that the JD paper was found dissimilar to ours anyway and there s no need to retract the JD paper but add a citation of our original paper. We thought we should submit evidence and our findings to PubPeer and other publication ethics watchdogs, but before doing that it would be nice and fair to Wiley, as one of our highly regarded publishers, their London headquarters (if capable of controlling their local deviated practices from the central office) to handle this case. We reexamined the JD paper including its data, as if we were duly diligent peer reviewers, and we found some evidence for the JD paper s questionable research practices. On 13 Sep 2018, we submitted further evidence to the Wiley s London headquarters. They responded to many of our queries about the status of their evaluation of this case -- still pending. On 20 Mar 2019, i.e., seven months later, we received a brief decision statement (71 words) seemingly relayed their local office s old message without new supporting evidence and reasons. We were so disappointed that Wiley s London headquarters did not give us information about how their re-evaluation was conducted and why they ignore our evidence for the *plagiarism* and *questionable research practices* in the JD article. As we donu2019t find any transparency and cogency in Wiley s decisions, we are now submitting our findings and evidence (piece by piece so that the authors and publisher of the JD paper won t miss or slip away in responding to any crucial points) to PubPeer, and subsequently other research ethics forums. The first piece of evidence is about the JD s rephrasing (and maintain the order of similar sentences) of our original paper. We ll submit the second piece of evidence next week, which will be about a questionable research practice we found in the JD paper. Afterwards, 12 more pieces of evidence will follow. Please watch here to see how this case unfolds. Thank you for your time, attention, and judgement. ![file] The first piece of evidence will be found completely at[ https: bit.ly 2TEeBRB]() , 
 **The following are our preliminary critical appraisal of the scientific issues in the suspected paper, which does contain questionable research practices (QRP):** **(1) Non-reproducible literature search results** We tried to repeat their literature search using the same search strategies and databases as specified in the suspected paper. We found their literature search results are not reproducible. The total number of retrievable records from all the specified databases was 856 in our search but it was reported to be 949 in the suspected paper. The numbers of retrievable records from individual databases were not reported (violated the PRISMA reporting guideline) and such mis-reporting would prevent others from tracking the accuracy of the search results. Total recordsuff1aPubMed (199) + Embase (428) + Web of Science (8) + WanFang (106 or 105) + VIP (15) + CNKI (100) = 856 or 855 The following is search strategies and records identified for each database: ![file] ![file] Web of Science ![file] WanFang ![file] or ![file] VIP ![file] CNKI ![file] ![file] and ![file] ![file] **(2) Questionable study selection leads to unreliable conclusion (see *Evidence No. 9*)** We checked the studies included in the suspected paper. We found 15 out of their 39 included studies should have been excluded according to the exclusion criteria (see Evidence No. 9) because such 15 studies did not report the exact types of diabetes or exact sample sizes. As such, more than a third of included studies were mistakenly included. It would be likely that such questionable study selection would lead to unreliable findings and conclusion. ![file] ![file] ![file] ![file] **(3)tMissing protocol registration (violating the PRISMA guideline)** No registered protocol was found for the study reported in the suspected paper. Such protocol registration is a common practice for meta-analysis in evidence-based medicine research. **(4)tQuestionable argumentation and conclusions** In addition to the textu2019s semantic similarity scores, our ***Evidence No. 6*** also indicate the similarity of the argumentation in both papers. Thereu2019s an interesting fallacy in the conclusions, i.e., while itu2019s claimed that the suspected paper is all about stress-related T2DM (claimed to be not exactly the same as the T2DM in our paper), the suspected paper concluded the findings of miRNAs as biomarkers of T2DM (NOT stress-related T2DM!). What a logical fallacy and a false claim! **(5)tUnreliable quality assessment due to their misuse of our quality checklist (see *Evidence No. 8*)** As the suspected paper not only copied our original checklists (see ***Evidence No. 1***) in verbatim but also copied our inadvertent typo errors in the checklists, it is questionable about whether the authors of the suspected paper understood our checklists and criteria to assess the quality of included studies. We tried to compare their results of quality assessment of included studies with those of our studies that has been recently updated (unpublished). We found that they misuse our checklists because the quality assessment of 13 out of the 15 commonly included studies (87%) was different between the suspected paper and our studies (see ***Evidence No. 8***). Weu2019ll submit the third piece of evidence in two weeks, which is the mentioned ***Evidence No. 1***: *Plagiarism of quality assessment checklist and study characteristics items*. And next will be the mentioned ***Evidence No. 8*** and ***Evidence No. 6***. Thank you for your time, attention, and judgement. , 
 ***Evidence No. 1*: Plagiarism of quality assessment checklist and study characteristics items.** Our checklist was originally developed by our team modified from the MIAME reporting guideline. The suspected paper copied all our checklist items (circled in orange colour) both copyright infringement and in verbatim that is evident of direct plagiarism. The plagiarism does not only exhibit in the checklist items but also in the study characteristics items. The MIAME and MIQE guidelines suggest minimum information that are required to report in microarray and PCR studies. The checklists were developed by our team for the quality assessment of miRNA meta-analysis; they are not available from the public guidelines. The MIAME guidelines do not use the same items as we used (see the following table). ![file] ![file] ![file] ***Evidence No. 1*: Plagiarism of quality assessment checklist and study characteristics items. (continued)** And the MIAME guidelines do not use the same codes, i.e., not reported (NR), sufficient (S) and insufficient (I), to assess the study quality. ![file] In the study characteristics table (see the following screenshots), the table structure and the headings of the suspected paper are the same as those presented in our paper (circled in blue and red colour). All these clearly show direct plagiarism. ![file] Next time we ll upload the mentioned ***Evidence No. 8*** and ***Evidence No. 6***. Thank you for your time, attention, and judgement. , 
 ***Evidence No. 6*: Nearly the same argumentation structure** These outlines show the nearly the same argumentation structures of both papers. In this comparison of outlines, same arguments between two papers are highlighted in red colour, and similar arguments are highlighted in brown colour. There are two additional findings (@1 and @2), one exposes the plagiarism, and another reveals the intention of authors to hide their plagiarism. In the first additional finding @1, the suspected paper talks about the problems of T2Du2019s miRNA profiles as the main argument for conducting this meta-analysis. *Among numerous different papers available to cite, the suspected papers cited the same references as cited in our paper in the same order. Similar finding was also found in Discussion part* **(see Table 1-2)**. In the second additional finding @2, the suspected paper mentions subgroup analysis in Methods in the same order as appeared in our paper, i.e., analyses on tissue types and then on species. But in the Results and Discussion sections, the suspected paper reported species first and then tissue types. Such order of analyses is deviated from the study plan in Methods. The deviation would not be any professional writing style unless it is trying to mask the plagiarism. ![file] ![file] ![file] ![file] Weu2019ll submit another piece of evidence in two weeks, which is the ***Evidence No. 2***: *Text alignment table showing the plagiarism of ideas and text in Methods section*. Thank you for your time, attention, and judgement. , 
 ***Evidence No. 2*: Text alignment table showing the plagiarism of ideas and text in Methods section** The suspected paper did not cite our paper in Methods but copied the whole Methods of ours. The text alignment table shows most of the sentences or phrases in the Methods section of the suspected paper are the same description or mean the same things (marked in the same color and same number) as in our paper. The listings of the numbers also reveal the structure of the text in both papers. ![file] ![file] ![file] ![file] ***Evidence No. 3*: The following text alignment tables showing the extent of plagiarism** Table 1 Plagiarised sentences (content) and language rephrasing (detailed information can be found in Evidence 4, our first upload) ![file] Besides the statistics as shown in Table 1, we also notice that the only differences of Introduction and Discussion between two papers are due to different topics (stress-related condition in the suspected paper vs. general conditions in our paper) only. It is noticeable that the equivalent sentences in Introduction and Discussion in the suspected paper did cite the same references as in the original sentences of our paper. Table 2. Plagiarised Figures and Tables (detailed information can be found in Evidence 4, our first upload) ![file] As shown in Table 2, all four Figures in Results of the suspected paper were found plagiarising our original figures with two in Results and the other two in Discussion. One out of two Tables in Results of the suspected paper plagiarised our Table in the Supplementary file of our paper. Eight out of nine Tables in our Supplementary file of the suspected paper copied our Tables (two in our Results and the other six in our Supplementary file). A detailed head-to-head comparison of the Figures and Tables is presented in Evidence 4, our first upload. And the MIAME check table shows the suspected paper fabricating something (see ***Evidence No. 1***). ***Evidence No. 5*: Improper and inadequate citations. The citation of our paper was only for the inconsistent results among studies mentioned in our paper, not for our methods, results and argumentation** ![file] ,