1 Introduction
Mainly caused by atherosclerosis,[1] [2] [3] [4] [5–7] [8]
Revascularization is the most effective method for the treatment of coronary heart disease. Although it cannot completely cure coronary heart disease, it can greatly improve CHD patients’ clinical symptoms, thus increasing their life quality and survival rate. At present, coronary artery reconstruction mainly involves coronary artery bypass grafting and percutaneous coronary intervention (PCI).[9] [10]
With the production and rapid development of the second generation sequencing, especially the application of RNA sequencing, long non-coding RNA (lncRNA) has gradually become a hot spot in the field of life science. The expression level of lncRNA in blood samples may be regarded as a prognostic and diagnostic biomarker. In order to analyze the effect of LncRNA on the prognosis of CHD after PCI more accurately, this study reviewed the literature on the relationship between lncRNA and prognosis in CHD patients after PCI, and applied meta-analysis to evaluate the relationship between lncRNA and prognosis in patients CHD after PCI.
2 Methods
2.1 Study registration
This meta-analysis protocol is based on the Preferred Reporting Items for Systematic Reviews and meta-analysis Protocols (PRISMA-P) statement guidelines. The protocol of the systematic review was registered on Open Science Framework, and the registration number is DOI 10.17605/OSF.IO/RAZ6J.
2.2 Literature retrieval
We searched China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, EMBASE, and all these electronic databases, without language restrictions. The PubMed search strategy was illustrated in details in Table 1 , and other electronic databases adopted similar search strategies.
Table 1 -
Search strategy (PubMed).
Number
Search terms
1
Coronary Disease [MeSH]
2
Coronary Heart Disease [Title/Abstract]
3
CHD[Title/Abstract]
4
Coronary Diseases[Title/Abstract]
5
Coronary Heart Diseases[Title/Abstract]
6
Disease, Coronary[Title/Abstract]
7
Disease, Coronary Heart[Title/Abstract]
8
Diseases, Coronary[Title/Abstract]
9
Diseases, Coronary Heart[Title/Abstract]
10
Heart Disease, Coronary[Title/Abstract]
11
Heart Diseases, Coronary[Title/Abstract]
12
Coronary Artery Disease[MeSH]
13
Arteriosclerosis, Coronary[Title/Abstract]
14
Atherosclerosis, Coronary[Title/Abstract]
15
Coronary Arteriosclerosis[Title/Abstract]
16
Coronary Atherosclerosis[Title/Abstract]
17
Arterioscleroses, Coronary[Title/Abstract]
18
Artery Disease, Coronary[Title/Abstract]
19
Artery Diseases, Coronary[Title/Abstract]
20
Atheroscleroses, Coronary[Title/Abstract]
21
Coronary Arterioscleroses[Title/Abstract]
22
Coronary Artery Diseases[Title/Abstract]
23
Coronary Atheroscleroses[Title/Abstract]
24
Disease, Coronary Artery[Title/Abstract]
25
Diseases, Coronary Artery[Title/Abstract]
26
OR/1-25
27
RNA, Long Untranslated[MeSH]
28
LINC RNA[Title/Abstract]
29
LincRNAs[Title/Abstract]
30
Long Intergenic Non-Protein Coding RNA[Title/Abstract]
31
Long Non-Coding RNA[Title/Abstract]
32
Long Non-Protein-Coding RNA[Title/Abstract]
33
Long Noncoding RNA[Title/Abstract]
34
Long ncRNA[Title/Abstract]
35
Long ncRNAs[Title/Abstract]
36
RNA, Long Non-Translated[Title/Abstract]
37
Long Intergenic Non Protein Coding RNA[Title/Abstract]
38
Long Non Coding RNA[Title/Abstract]
39
Long Non Protein Coding RNA[Title/Abstract]
40
Long Non-Translated RNA[Title/Abstract]
41
Long Untranslated RNA[Title/Abstract]
42
Non-Coding RNA, Long[Title/Abstract]
43
Non-Protein-Coding RNA, Long[Title/Abstract]
44
Non-Translated RNA, Long[Title/Abstract]
45
Noncoding RNA, Long[Title/Abstract]
46
RNA, Long Non Translated[Title/Abstract]
47
RNA, Long Non-Coding[Title/Abstract]
48
RNA, Long Non-Protein-Coding[Title/Abstract]
49
RNA, Long Noncoding[Title/Abstract]
50
Untranslated RNA, Long[Title/Abstract]
51
ncRNA, Long[Title/Abstract]
52
ncRNAs, Long[Title/Abstract]
53
OR/27–52
54
Percutaneous Coronary Intervention[MeSH]
55
Percutaneous Coronary Revascularization[Title/Abstract]
56
Coronary Intervention, Percutaneous[Title/Abstract]
57
Coronary Interventions, Percutaneous[Title/Abstract]
58
Coronary Revascularization, Percutaneous[Title/Abstract]
59
Coronary Revascularizations, Percutaneous[Title/Abstract]
60
Intervention, Percutaneous Coronary[Title/Abstract]
61
Interventions, Percutaneous Coronary[Title/Abstract]
62
Percutaneous Coronary Interventions[Title/Abstract]
63
Percutaneous Coronary Revascularizations[Title/Abstract]
64
Revascularization, Percutaneous Coronary[Title/Abstract]
65
Revascularizations, Percutaneous Coronary[Title/Abstract]
66
OR/54–65
67
Prognos∗ [Title/Abstract]
68
Survival[Title/Abstract]
69
OR/67–68
70
26 AND 53 AND 66 AND 69
2.3 Inclusion criteria for study selection
(1) CHD was diagnosed based the coronary artery score of the American College of Cardiology.[11]
(2) LncRNA was expressed in serum or plasma.
(3) Reported LncRNA survival-related data.
(4) Patients were divided into LncRNA positive and LncRNA negative.
(5) Published as full-text articles.
Papers without sufficient data, literature reviews, case series, conference summaries, animal studies, and other unrelated studies were excluded from the analysis.
2.4 Data collection and analysis
2.4.1 Selection of studies
First of all, 2 researchers read and checked out the titles and abstracts of relevant literatures independently. After excluding the literatures that obviously do not meet the inclusion criteria, and downloading the remaining literatures for further full-text reading, the literatures that really meet the inclusion criteria were enrolled. The 2 researchers cross-checked the results. A self-made data extraction form was made to extract the required information from the included literatures. If there are differences, a third party would involve the discussion or consultation in this study. The flowchart of the study selection (Fig. 1 ) could provide a detailed description.
Figure 1: Flow diagram showing literature filtration process.
2.4.2 Data extraction
The extracted information includes the title of the paper, name of the first author, journal, year of publication, country, race, age, sex, sample size, LncRNA detection method, LncRNA type, overall survival (OS), hazard ratio (HRs), and 95% confidence interval (CIs). If we can’t access survival data directly, we would obtain HRs and 95% CIs from the Kaplan–Meier survival curves by referring to Engauge Digitizer version 4.1 (http://digitizer.sourceforge.net/
2.5 Literature quality evaluation
As a bias risk assessment tool for observational studies recommended by Cochrane Collaboration, Newcastle-Ottawa quality Assessment scale (NOS) was adopted to evaluate the quality of the included studies.[12] [13]
2.6 Measures of prognosis
OS was taken as prognostic outcomes, and the results were expressed as HRs with 95% CIs.
2.7 Management of missing data
If there exists insufficient or missing data in the literature, we would only analyze the currently available data and discuss its potential value.
2.8 Statistical analysis
Statistical analysis was performed with STATA 14.0 (STATA Corporation, College Station, TX) and RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The 95% CIs and HRs were utilized to evaluate the relationship among LncRNA expression and OS. First of all, chi-squared test and I 2 I 2 ≤ 25% indicated that the heterogeneity was small, 25% < I 2 ≤ 50% marked moderate heterogeneity, and I 2 > 50% revealed that there was a high degree of heterogeneity among the research results. When there is no heterogeneity among the research results, the fixed effect model is adopted for meta-analysis. When there exists heterogeneity among the research results, the stability of the conclusion is verified, and the random effect model is decided for meta-analysis.
2.9 Additional analysis
2.9.1 Subgroup analysis
According to the detection methods of LncRNA, ethnicity, the source of survival data, and type of LncRNA, we analyzed the subgroup.
2.9.2 Sensitivity analysis
Sensitivity analysis was conducted to assess the impact of individual studies on the overall merger value.
2.9.3 Reporting bias
If the number of studies included in a certain outcome index was no <10, funnel chart could be used to evaluate publication bias.[14,15]
2.10 Ethics
Our research data were derived from published literatures, because there was no patient recruitment and personal information collection. Therefore, ethical approval was not required.
3 Discussion
Cardiovascular disease, especially CHD, is still the leading cause of death worldwide, resulting in a significant social and economic burden. Although drug therapy, PCI, and other treatments can improve the prognosis of CHD, the mortality rate is still very high.[16] [17] [18]
In the past 10 years, the research on lncRNA in terms of the occurrence and development of CHD and other heart diseases has become more and more in-depth. LncRNA not only regulates cell proliferation, apoptosis, injury, autophagy, and differentiation, but also participates in the occurrence and development of a variety of cardiovascular diseases through different molecular mechanism. Therefore, it can be regarded as a new regulatory factor for diagnosis and treatment.
Some plasma LncRNA, such as ANRIL, LincRNA-p21, and myocardial infarction-related transcription factor-1, significantly increases in atherosclerosis and may play an important role in the pathogenesis of atherosclerosis.[19–22] [23] [24]
Author contributions
Conceptualization: Ling Ma, Fei Wang.
Data curation: Xiaoqing Cai, Peng Zhang.
Resources: Piqi Jiao.
Software: Yan Liu, Bin Yuan, Hongbin Liu.
Writing – original draft: Ling Ma, Fei Wang.
Writing – review & editing: Ling Ma, Fei Wang.
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