Unveiling the Hidden Causal Links: Skin Flora and Cutaneous Melanoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Dec 26

PMID 39723372

Authors

Zexin Zhang

Wenfeng Wu

Jiajia Lin

Hongyi Li

Affiliations

Soon will be listed here.

Abstract

Objective: The presence of skin flora (SF) has been identified as a significant factor in the onset and progression of cutaneous melanoma (CM). However, the vast diversity and abundance of SF present challenges to fully understanding the causal relationship between SF and CM.

Methods: A Two Sample Mendelian Randomization (TSMR) analysis was conducted to investigating the causal relationship between SF and CM. The Inverse-Variance Weighted (IVW) method was utilized as the primary approach to assess the causal relationship under investigation. Furthermore, an independent external cohort was employed to validate the initial findings, followed by a meta-analysis of the consolidated results. To address potential confounding factors related to the influence of SF on CM, a Multivariate Mendelian Randomization (MVMR) analysis was also conducted. Finally, a Reverse Mendelian Randomization (RMR) was conducted to further validate the causal association.

Results: TSMR results showed that 9 SF have a causal relationship with CM in the training cohort. Although these 9 SF weren't confirmed in the testing cohort, 4 SF remained significant in the meta-analysis after integrating results from both cohorts. MVMR analysis indicated that 3 SF were still significantly associated with CM after accounting for the interactions between different SF in the training cohort. No reverse causal relationship was identified in RMR analysis.

Conclusion: A total of 9 SF were identified as having a potential causal relationship with CM; however, a large randomized controlled trial is needed to verify these results.

References

Fu X, Liu B, Wang Y, Li J, Zhu P, Li T . Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression. Cell Death Dis. 2020; 11(4):246. PMC: 7171093. DOI: 10.1038/s41419-020-2440-1. View

Tzeng A, Sangwan N, Jia M, Liu C, Keslar K, Downs-Kelly E . Human breast microbiome correlates with prognostic features and immunological signatures in breast cancer. Genome Med. 2021; 13(1):60. PMC: 8052771. DOI: 10.1186/s13073-021-00874-2. View

Smythe P, Wilkinson H . The Skin Microbiome: Current Landscape and Future Opportunities. Int J Mol Sci. 2023; 24(4). PMC: 9963692. DOI: 10.3390/ijms24043950. View

Cavarretta I, Ferrarese R, Cazzaniga W, Saita D, Luciano R, Ceresola E . The Microbiome of the Prostate Tumor Microenvironment. Eur Urol. 2017; 72(4):625-631. DOI: 10.1016/j.eururo.2017.03.029. View

Tang S, Prem A, Tjokrosurjo J, Sary M, Van Bel M, Rodrigues-Hoffmann A . The canine skin and ear microbiome: A comprehensive survey of pathogens implicated in canine skin and ear infections using a novel next-generation-sequencing-based assay. Vet Microbiol. 2020; 247:108764. DOI: 10.1016/j.vetmic.2020.108764. View

Walujkar S, Dhotre D, Marathe N, Lawate P, Bharadwaj R, Shouche Y . Characterization of bacterial community shift in human Ulcerative Colitis patients revealed by Illumina based 16S rRNA gene amplicon sequencing. Gut Pathog. 2014; 6:22. PMC: 4094692. DOI: 10.1186/1757-4749-6-22. View

Moitinho-Silva L, Degenhardt F, Rodriguez E, Emmert H, Juzenas S, Mobus L . Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota. Nat Commun. 2022; 13(1):6204. PMC: 9582029. DOI: 10.1038/s41467-022-33906-5. View

Harris-Tryon T, Grice E . Microbiota and maintenance of skin barrier function. Science. 2022; 376(6596):940-945. DOI: 10.1126/science.abo0693. View

Zheng Y, Hunt R, Villaruz A, Fisher E, Liu R, Liu Q . Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe. 2022; 30(3):301-313.e9. PMC: 8917079. DOI: 10.1016/j.chom.2022.01.004. View

10.

Wu R, Yu I, Tokumaru Y, Asaoka M, Oshi M, Yan L . Elevated bile acid metabolism and microbiome are associated with suppressed cell proliferation and better survival in breast cancer. Am J Cancer Res. 2022; 12(11):5271-5285. PMC: 9729904. View

11.

Woo Y, Cho S, Lee J, Kim H . The Human Microbiota and Skin Cancer. Int J Mol Sci. 2022; 23(3). PMC: 8837078. DOI: 10.3390/ijms23031813. View

12.

Kumar P, Brazel D, deRogatis J, Valerin J, Whiteson K, Chow W . The cure from within? a review of the microbiome and diet in melanoma. Cancer Metastasis Rev. 2022; 41(2):261-280. PMC: 9042647. DOI: 10.1007/s10555-022-10029-3. View

13.

Sherwani M, Tufail S, Muzaffar A, Yusuf N . The skin microbiome and immune system: Potential target for chemoprevention?. Photodermatol Photoimmunol Photomed. 2017; 34(1):25-34. PMC: 7289174. DOI: 10.1111/phpp.12334. View

14.

Sessler D, Imrey P . Clinical Research Methodology 2: Observational Clinical Research. Anesth Analg. 2015; 121(4):1043-1051. DOI: 10.1213/ANE.0000000000000861. View

15.

Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N . European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022. Eur J Cancer. 2022; 170:236-255. DOI: 10.1016/j.ejca.2022.03.008. View

16.

Timar J, Ladanyi A . Molecular Pathology of Skin Melanoma: Epidemiology, Differential Diagnostics, Prognosis and Therapy Prediction. Int J Mol Sci. 2022; 23(10). PMC: 9140388. DOI: 10.3390/ijms23105384. View

17.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

18.

Shin N, Whon T, Bae J . Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015; 33(9):496-503. DOI: 10.1016/j.tibtech.2015.06.011. View

19.

Balch C, Gershenwald J, Soong S, Thompson J, Ding S, Byrd D . Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010; 28(14):2452-9. PMC: 2982783. DOI: 10.1200/JCO.2009.27.1627. View

20.

Byrd A, Belkaid Y, Segre J . The human skin microbiome. Nat Rev Microbiol. 2018; 16(3):143-155. DOI: 10.1038/nrmicro.2017.157. View