Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis

BackgroundA hallmark of gastrointestinal cancer, especially pancreatic cancer, is the dense stromal tumor microenvironment in which cancer-associated fibroblasts (CAFs) represent the major stromal cell type. Preclinical studies have demonstrated that depletion of fibroblast a...

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Main Authors: Yoshiaki Sunami, Ulrich Ronellenfitsch, Jorg Kleeff, Artur Rebelo
Format: Article
Language:English
Published: JMIR Publications 2023-04-01
Series:JMIR Research Protocols
Online Access:https://www.researchprotocols.org/2023/1/e45176
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author Yoshiaki Sunami
Ulrich Ronellenfitsch
Jorg Kleeff
Artur Rebelo
author_facet Yoshiaki Sunami
Ulrich Ronellenfitsch
Jorg Kleeff
Artur Rebelo
author_sort Yoshiaki Sunami
collection DOAJ
description BackgroundA hallmark of gastrointestinal cancer, especially pancreatic cancer, is the dense stromal tumor microenvironment in which cancer-associated fibroblasts (CAFs) represent the major stromal cell type. Preclinical studies have demonstrated that depletion of fibroblast activation protein (FAP)–positive CAFs results in increased survival. ObjectiveWe present the protocol for a systematic review and meta-analysis that aim to assess the currently available evidence on the effect of FAP expression on survival and clinical characteristics in gastrointestinal cancers. MethodsThe literature search and data analysis will be conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. The databases PubMed/MEDLINE, Web of Science Core Collection, Cochrane Library, and ClinicalTrials.gov will be searched via their respective online search engines. A meta-analysis comparing patients with and without FAP overexpression with the following outcomes will be performed: postoperative survival (overall and median survival; 1-, 2-, 3-, and 5-year survival rates), histological differentiation (grading), local tumor invasion, lymph node metastases, and distant metastases. Odds ratios will be calculated for binary data, and weighted mean differences and relative SD differences will be determined for continuous data. The 95% CI, heterogeneity measures, and statistical significance will be reported for each outcome. The chi-square and Kruskal-Wallis tests will be used to evaluate statistical significance. A P value of <.05 will be considered statistically significant. ResultsDatabase searches will commence in April 2023. The meta-analysis will be completed by December 2023. ConclusionsIn recent years, several publications on FAP overexpression in gastrointestinal tumors have been published. The only published meta-analysis on this topic dates to 2015. It included 15 studies on various solid tumors and only 8 studies focusing exclusively on gastrointestinal tumors. The expected results of the present analysis will provide new evidence on the prognostic value of FAP in gastrointestinal tumors and thereby support health care professionals and patients in their decision-making. Trial RegistrationPROSPERO CRD42022372194; https://tinyurl.com/352ae8b8 International Registered Report Identifier (IRRID)PRR1-10.2196/45176
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spelling doaj.art-64817988048d4b79af1b3973ab00bc442023-08-28T23:57:35ZengJMIR PublicationsJMIR Research Protocols1929-07482023-04-0112e4517610.2196/45176Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysisYoshiaki Sunamihttps://orcid.org/0000-0002-1235-7512Ulrich Ronellenfitschhttps://orcid.org/0000-0003-1107-813XJorg Kleeffhttps://orcid.org/0000-0003-3432-6669Artur Rebelohttps://orcid.org/0000-0002-5267-079X BackgroundA hallmark of gastrointestinal cancer, especially pancreatic cancer, is the dense stromal tumor microenvironment in which cancer-associated fibroblasts (CAFs) represent the major stromal cell type. Preclinical studies have demonstrated that depletion of fibroblast activation protein (FAP)–positive CAFs results in increased survival. ObjectiveWe present the protocol for a systematic review and meta-analysis that aim to assess the currently available evidence on the effect of FAP expression on survival and clinical characteristics in gastrointestinal cancers. MethodsThe literature search and data analysis will be conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. The databases PubMed/MEDLINE, Web of Science Core Collection, Cochrane Library, and ClinicalTrials.gov will be searched via their respective online search engines. A meta-analysis comparing patients with and without FAP overexpression with the following outcomes will be performed: postoperative survival (overall and median survival; 1-, 2-, 3-, and 5-year survival rates), histological differentiation (grading), local tumor invasion, lymph node metastases, and distant metastases. Odds ratios will be calculated for binary data, and weighted mean differences and relative SD differences will be determined for continuous data. The 95% CI, heterogeneity measures, and statistical significance will be reported for each outcome. The chi-square and Kruskal-Wallis tests will be used to evaluate statistical significance. A P value of <.05 will be considered statistically significant. ResultsDatabase searches will commence in April 2023. The meta-analysis will be completed by December 2023. ConclusionsIn recent years, several publications on FAP overexpression in gastrointestinal tumors have been published. The only published meta-analysis on this topic dates to 2015. It included 15 studies on various solid tumors and only 8 studies focusing exclusively on gastrointestinal tumors. The expected results of the present analysis will provide new evidence on the prognostic value of FAP in gastrointestinal tumors and thereby support health care professionals and patients in their decision-making. Trial RegistrationPROSPERO CRD42022372194; https://tinyurl.com/352ae8b8 International Registered Report Identifier (IRRID)PRR1-10.2196/45176https://www.researchprotocols.org/2023/1/e45176
spellingShingle Yoshiaki Sunami
Ulrich Ronellenfitsch
Jorg Kleeff
Artur Rebelo
Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
JMIR Research Protocols
title Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
title_full Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
title_fullStr Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
title_full_unstemmed Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
title_short Fibroblast Activation Protein Overexpression in Gastrointestinal Tumors: Protocol for a Systematic Review and Meta-analysis
title_sort fibroblast activation protein overexpression in gastrointestinal tumors protocol for a systematic review and meta analysis
url https://www.researchprotocols.org/2023/1/e45176
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