This scoping review will be conducted and reported in accordance with the Joanna Briggs Institute Manual for Evidence Synthesis and PRISMA Extension for Scoping Reviews (PRISMA-ScR).
Studies will be included if they were: reported in English, included patients with cancer of any type at any stage, used an epigenome-wide approach and performed a DNA methylation array, used at least one AI method to explore the association between aberrant methylation and cancer prognosis (i.e., survival, progression, therapy responses).
We will exclude reviews, studies using a candidate-gene approach, multi-omic studies, and studies only investigating diagnostic methylation biomarkers.
Information source and search strategy
We plan to search for eligible studies published between 1 January 1990 and 31 September 2021 in the following databases: PubMed, Web of Science, and Embase. The final search results will be exported into EndNote, and duplicates will be subsequently removed. The electronic database search will be supplemented by searching web search engines (Google Scholar, ClinicalTrials.gov, and Grey Matters) to identify gray literature. References of relevant reviews and full-text articles will be screened for additional studies.
The search strategy will be formulated using both MeSH terms and free-text words related to cancer, AI, epigenetic signatures, and prognosis. Filters will be applied to restrict studies conducted in humans and written in English.
The search term list is as follows:
("neoplasms"[Mesh] OR "cancer" [Text Word] OR “tumor*” [Text Word] OR “carcinoma*” [Text Word] OR “pan-cancer” [Text Word] OR “adenocarcinoma*” [Text Word] OR “leukemia” [Text Word])
(“ai artificial intelligence [Mesh]” OR “machine learning [Mesh]” OR “decision support [Text word]” OR “clustering [Text word]” OR “deep learning [Text word]” OR “neural network*”)
#3 Epigenetic signatures
("methylation"[Mesh] OR "dna methylation*"[Mesh] OR “methylat*” [Text Word] OR “epigenetic*” [Text Word] OR “epigenetic marker*” [Text Word] OR “DNA-methylation” [Text Word] OR “hypermethylat*”[Text Word] OR “hypomethylat*” [Text Word] OR “CpG” [Text Word] OR “epigenome-wide” [Text Word] OR “methylation-based” [Text Word])
("mortality"[Mesh] OR "survival"[Mesh] OR "survival analysis"[Mesh] OR “mortality”[Text Word] OR “survival” [Text Word] OR “prognos*” [Text Word] OR “predict*” [Text Word] OR “outcome*” [Text Word] OR “recurr*”[Text Word])
Study selection process
The titles and abstracts of retrieved studies will be firstly screened for eligibility by one author. Potentially eligible studies will be retained for full text search, and inclusion will be determined by reading the full text of these studies
A draft charting table/form for data extraction and explanation
The follow study-level key information will be extracted onto a spreadsheet:
1. First author, year of publication, study origin,
2. Endpoints of interest
3. Anatomical site of cancer, data source, data size, types of biological specimens
(a) Data processing methods and procedures
(b) Type of AI methods
(c) Validation methods
5. Performance measurement
6. Limitations of the study as reported by the authors
Critical appraisal of individual sources of evidence
The reporting quality of all included studies will be assessed by the Reporting recommendations for tumor marker prognostic studies (REMARK). Besides, if a risk prediction model was developed in a study, its reporting quality will be additionally assessed by Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): The TRIPOD statement, and its methodological quality will be assessed by PROBAST: A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies.