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      Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis

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          Abstract

          Leucine-rich G protein-coupled receptor 5 ( LGR5) is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/ clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigate correlation between LGR5 expression and outcomes of cancer patients under study through a systematic review and meta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopus databases until December 21, 2022. This study was conducted to examine correlation between LGR5 expression and different clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis was conducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly, high-level expression of LGR5 was related to poor prognosis in terms of OS, higher tumor stage, presence of distant metastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors, including the study area, evaluation method, and type of cancer, can influence the correlation between LGR5 expression and negative prognosis in cancer patients. According to the results of our study, LGR5 overexpression was related to poor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patients with high LGR5 expression. In conclusion, LGR5 may serve as a potential prognostic marker for predicting survival in certain cancer types.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.

            Andreas Stang (2010)
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              The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

              Alessandro Liberati, Douglas G. Altman, Jennifer Tetzlaff … (2010)
              Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell J
                Journal ID (iso-abbrev): Cell J
                Journal ID (publisher-id): Royan Institute
                Title: Cell Journal (Yakhteh)
                Publisher: Royan Institute
                ISSN (Print): 2228-5806
                ISSN (Electronic): 2228-5814
                Publication date (Print): January 2024
                Publication date (Electronic): 31 January 2024
                Volume: 26
                Issue: 1
                Pages: 1-12
                Affiliations
                [1. ]Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
                [2. ]Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, Isfahan University of Medical Sciences, Isfahan, Iran
                [3. ]Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
                Author notes
                [* Corresponding Address: ] P.O.Box: 8174673461 Department of Genetics and Molecular Biology School of Medicine Isfahan University of Medical Sciences IsfahanIran Email: r_salehi@ 123456med.mui.ac.ir
                Article
                Other ID: Cell-J-26-1
                DOI: 10.22074/CELLJ.2023.2010157.1396
                PMC ID: 10864775
                PubMed ID: 38351725
                SO-VID: db4d7746-0460-48fa-9731-09b6b6cc10e5
                Copyright © Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 August 2023
                Date revision received : 8 November 2023
                Date accepted : 18 November 2023
                Categories
                Subject: Systematic Review
                Subject: Cancer
                Subject: Biochemistry
                Custom metadata
                Citation Ghobakhloo S, Khoshhali M, Vatandoost N, Jafarpour S, Niazmand A, Nedaeinia R, Salehi R. Clinical implications and prognostic value of leucinerich g protein-coupled receptor 5 expression as a cancer stem cell marker in malignancies: a systematic review and meta-analysis. Cell J. 2024; 26(1): 1-12. doi: 10.22074/CELLJ.2023.2010157.1396 This open-access article has been published under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0).

                Keywords: cancer stem cells,clinicopathological features,lgr5,prognostic marker
                Data availability:
                Keywords: cancer stem cells, clinicopathological features, lgr5, prognostic marker

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