A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Study Selection and Data Extraction
3. Results
4. Detailed Results and Discussion
4.1. Diagnostic Epigenetic Biomarkers in NSCLC
4.1.1. Exhaled Breath Condensate
4.1.2. Bronchial Secretions
4.1.3. Peripheral Blood
4.1.4. Exosomes for Detection of NSCLC
4.2. Prognostic Epigenetic Biomarkers in NSCLC
4.2.1. From a Single Gene to Genome-Wide DNA Methylation Profiling
4.2.2. Non-Coding RNAs’ Expression Profiling
4.3. Epigenetic-Based Therapy for NSCLC
4.3.1. Natural Substances and Their Derivatives
4.3.2. Synthetic Epigenetic Modalities
4.3.3. Perspectives on Epigenetic Therapy for NSCLC
4.4. Summary and Future Strategies for Epigenetic Research on NSCLC
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Topic | No. | Item | Location Where Item Is Reported |
---|---|---|---|
TITLE | |||
Title | 1 | Identify the report as a systematic review. | page 1 |
ABSTRACT | |||
Abstract | 2 | See PRISMA 2020 for Abstracts checklist. | |
INTRODUCTION | |||
Rationale | 3 | Describe the rationale for the review in the context of existing knowledge. | pages 2 and 3 |
Objectives | 4 | Provide an explicit statement of the objective(s) or question(s) the review addresses. | page 3 |
METHODS | |||
Eligibility criteria | 5 | Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. | page 7 |
Information sources | 6 | Specify all databases, registers, websites, organizations, reference lists, and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. | page 3 |
Search strategy | 7 | Present the full search strategies for all databases, registers, and websites, including any filters and limits used. | pages 6 and 7 |
Selection process | 8 | Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. | pages 7 and 8 |
Data collection process | 9 | Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. | pages 7 and 8 |
Data items | 10a | List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect. | pages 7 and 8 |
10b | List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. | N/A | |
Study risk of bias assessment | 11 | Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. | page 8 |
Effect measures | 12 | Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results. | page 8 |
Synthesis methods | 13a | Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item 5)). | N/A |
13b | Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. | N/A | |
13c | Describe any methods used to tabulate or visually display results of individual studies and syntheses. | N/A | |
13d | Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used. | N/A | |
13e | Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression). | N/A | |
13f | Describe any sensitivity analyses conducted to assess robustness of the synthesized results. | N/A | |
Reporting bias assessment | 14 | Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). | N/A |
Certainty assessment | 15 | Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. | N/A |
RESULTS | |||
Study selection | 16a | Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. | pages 9–11 |
16b | Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. | N/A | |
Study characteristics | 17 | Cite each included study and present its characteristics. | pages 12–23 |
Risk of bias in studies | 18 | Present assessments of risk of bias for each included study. | page 10 |
Results of individual studies | 19 | For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g., confidence/credible interval), ideally using structured tables or plots. | pages 12–23 |
Results of syntheses | 20a | For each synthesis, briefly summarize the characteristics and risk of bias among contributing studies. | N/A |
20b | Present results of all statistical syntheses conducted. If meta-analysis was conducted, present for each the summary estimate and its precision (e.g., confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. | N/A | |
20c | Present results of all investigations of possible causes of heterogeneity among study results. | N/A | |
20d | Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. | N/A | |
Reporting biases | 21 | Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. | N/A |
Certainty of evidence | 22 | Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. | N/A |
DISCUSSION | |||
Discussion | 23a | Provide a general interpretation of the results in the context of other evidence. | pages 12–23 |
23b | Discuss any limitations of the evidence included in the review. | pages 12–23 | |
23c | Discuss any limitations of the review processes used. | N/A | |
23d | Discuss implications of the results for practice, policy, and future research. | pages 24–26 | |
OTHER INFORMATION | |||
Registration and protocol | 24a | Provide registration information for the review, including register name and registration number, or state that the review was not registered. | N/A |
24b | Indicate where the review protocol can be accessed, or state that a protocol was not prepared. | N/A | |
24c | Describe and explain any amendments to information provided at registration or in the protocol. | N/A | |
Support | 25 | Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. | N/A |
Competing interests | 26 | Declare any competing interests of review authors. | N/A |
Availability of data, code, and other materials | 27 | Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review. | N/A |
Database | PubMed |
---|---|
Date | from inception to 22 December 2022 |
#1 | “lung cancer epigenetic” AND ((DNA methylation diagnosis) OR miRNA diagnosis) OR lncRNA diagnosis) OR (liquid biopsy AND lung cancer diagnosis)) OR exhaled breath condensate) OR methylation detection methods) OR DNA methylation prognosis) OR miRNA prognosis) OR lncRNA prognosis) OR epigenetic-targeted therapy) OR novel therapeutics) OR clinical trials) OR preclinical trials) OR nutriceuticals) AND full text[sb] AND Humans[MeSH] AND English[lang]) |
#2 | (((NSCLC diagnosis) AND (DNA methylation)) OR ((miRNA) AND (NSCLC diagnosis)) OR ((lncRNA) AND (NSCLC diagnosis)) OR ((liquid biopsy) AND (NSCLC diagnosis)) OR ((exhaled breath condensate) AND (NSCLC diagnosis)) AND full text[sb] AND AND Humans[MeSH] AND English[lang]) |
#3 | (((NSCLC prognosis) AND (DNA methylation)) OR ((miRNA) AND (NSCLC prognosis)) OR ((lncRNA) AND (NSCLC prognosis)) AND full text[sb] AND Humans[MeSH] AND English[lang]) |
#4 | (((NSCLC therapy) AND (DNA methylation)) OR ((miRNA) AND (NSCLC therapy)) OR ((lncRNA) AND (NSCLC therapy)) OR ((epigenetic therapy) AND (lung cancer)) OR ((novel therapeutics) AND (NSCLC)) OR ((epigenetic therapy) AND (clinical trial)) OR ((epigenetic therapy) AND (preclinical trial)) OR ((epigenetic therapy) AND (nutriceuticals)) AND full text[sb] AND Humans[MeSH] AND English[lang]) |
Search Terms Used in the Systematic Review | |
---|---|
Lung cancer epigenetics | DNA methylation diagnosis |
NSCLC diagnosis | miRNA diagnosis |
NSCLC prognosis | lncRNA diagnosis |
NSCLC therapy | Epigenetic therapy |
Liquid biopsy | miRNA prognosis |
Lung cancer diagnosis | lncRNA prognosis |
Exhaled breath condensate | Epigenetic-targeted therapy |
Methylation detection methods | Novel therapeutics |
DNA methylation prognosis | Nutriceuticals |
Measures and Methods for the Studies Included in the Systematic Review | ||
---|---|---|
Chapter | Measures | Methods |
Section 4.1 | Diagnostic epigenetic biomarkers in NSCLC | |
Cancerous vs. non-cancerous tissue | Sensitivity and specificity as given in AUC measures | |
Section 4.1.1 | Exhaled breath condensate findings | Proportion in study population |
Section 4.1.2 | Bronchial secretions | Sensitivity and specificity as given in AUC measures |
Section 4.1.3 | Peripheral blood | Sensitivity and specificity |
Section 4.1.4 | Exosomes for detection of NSCLC | Size and concentration |
Section 4.2 | Prognostic epigenetic biomarkers in NSCLC | |
Classical survival parameters since diagnosis | Overall survival | |
Section 4.2.1 | Single-gene/genome-wide DNA methylation profiling | Overall survival |
Section 4.2.2 | Non-coding RNA expression profiling | Survival parameters |
Section 4.3 | Epigenetic-based therapy for NSCLC | |
Efficacy of/response to treatment | Measurement of tumor load | |
Section 4.3.1 | Natural substances and their derivatives | Expression vs. tumor load/apoptosis/growth/metastasis |
Section 4.3.2 | Synthetic epigenetic modalities | Inhibition of tumor cell growth and metastases |
Results of Single-Gene/Genome-Wide DNA Methylation Profiling | |
---|---|
Methylation | Result |
DAPK1 [29] and TUSC3 [30] in NSCLC | Improved overall survival |
P16/INK4a and BRCA1 [31] in adenocarcinoma | Shorter overall survival |
RARβ [31] in adenocarcinoma | Longer overall survival |
HOXA2 and HOXA10 [32] in squamous cell carcinoma | Shorter overall survival |
HOXA9 in NSCLC lifelong non-smokers [33] | Poor recurrence-free survival |
NPTX1 in NSCLC [34] | Shorter overall survival |
PTPRH in adenocarcinoma [35] | Poor prognosis (OS) |
AGTRL, ALDH1A3, BDKRB1, CTSE, EFNA2, NFAM1, SEMA4A, and TMEM129 in adenocarcinoma [36] | Poor prognosis (OS) |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sulewska, A.; Pilz, L.; Manegold, C.; Ramlau, R.; Charkiewicz, R.; Niklinski, J. A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives. Cells 2023, 12, 905. https://doi.org/10.3390/cells12060905
Sulewska A, Pilz L, Manegold C, Ramlau R, Charkiewicz R, Niklinski J. A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives. Cells. 2023; 12(6):905. https://doi.org/10.3390/cells12060905
Chicago/Turabian StyleSulewska, Anetta, Lothar Pilz, Christian Manegold, Rodryg Ramlau, Radoslaw Charkiewicz, and Jacek Niklinski. 2023. "A Systematic Review of Progress toward Unlocking the Power of Epigenetics in NSCLC: Latest Updates and Perspectives" Cells 12, no. 6: 905. https://doi.org/10.3390/cells12060905