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Abstract

Purpose: In recent years, microbiome research has made significant progress in under-standing the relationship between human microbiota and pulmonary diseases. The lung and gut microbiota have received extensive attention in lung cancer research. Multiple studies have shown that dysregulation of the lung and gut microbiota is closely related to the occurrence and progression of lung cancer. The skin is the largest organ of the human body, as the first line of defense, it undertakes multiple functions such as de-fending against external pathogens and regulating body temperature and feeling. A complex and diverse microbial community also exists on the skin surface; however, the role of the skin microbiota in cancer has not been fully investigated. In particular, there is almost no research on the causal relationship between skin microbiota and lung can-cer.

Methods: In this Two-sample Mendelian randomization (MR) analysis study, we com-piled genome-wide association studies (GWAS) data on 150 different immune cell traits from 597 individuals of European ancestry. Additionally, Data on lung cancer were ob-tained from the FinnGen GWAS database to delve deeper into the potential causal rela-tionship between skin microbiome characteristics and lung cancer. In our MR Analysis, the inverse variance weighting (IVW) method is the main method, supplemented by MR-Egger regression, weighted median (WM), Simple Mode, and weighted mode. In addition, the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and remain-one analysis were used to identify heterogeneity and pleiotropy, to ensure the reliability and stability of the research results.

Results: In studying the relationship between lung cancer and skin microbiota, we found that there are different interactions between lung cancer and specific types of skin microbiota. In the forward Mendelian randomization analysis, we included skin micro-biota as the exposure factor and each subtype of lung cancer (including Non-small cell lung cancer, Squamous cell carcinoma, Adenocarcinoma, and Small cell lung cancer) as the outcome factor. A total of 11 microbiota were found to be significantly associated with non-small cell lung cancer (NSCLC), of which 6 were protective and 5 were associated with increased risk of NSCLC. These micro biota are classified into 5 genera, 2 families, and 2 orders. For lung squamous cell carcinoma (LUSC), 5 related micro flora were identified, of which 3 showed protective effects and 2 were regarded as risk fac-tors. These microflora included 4 Genus and 1 Class. In the lung adenocarcinoma (LUAD) study, 13 significantly related microbial groups were found, of which 3 have protective effects and 10 are related to increased risk. These microbial groups are classi-fied into 7 genera, 2 Order, and 2 families. In the study of small cell lung cancer (SCLC), 6 microbiota were found to be significantly associated with the disease, of which 1 had a protective effect and 5 were considered to increase the risk. These mi-crobiota are classified into 5 genera and 1 family. In this study, we also used the reverse Mendelian randomized analysis method to explore the effects of various subtypes of lung cancer (including NSCLC, LUSC, LUAD, and SCLC) on the skin microbiota. The results showed no statistically significant causal relationship was found on the path from lung cancer to skin microbiota.

Conclusions: Our study confirms a potential causal relationship between skin microbi-ota and lung cancer, suggesting that these microbiota play a role in the progression of lung cancer. This discovery provides a new perspective on how skin microbiota affects lung cancer and lays a foundation for developing targeted diagnostic and treatment strategies for lung cancer in the future.