尽管免疫治疗，特别是免疫检查点阻断，作为间皮瘤 (MMe) 治疗方法受到了越来越多的关注，但它的疗效和耐受性仍然受到质疑。免疫治疗产生不同反应的一个潜在解释是大肠和肿瘤内微生物群落，然而，这些方面在 MMe 中仍未被充分探索。本文强调了癌瘤内微生物群落作为 MMe 的新潜在预后指标。在 cBioPortal 上对 86 名 MMe 患者的 TCGA 数据进行了定制分析。中位总生存期用于将患者分为“低生存者”和“高生存者”。对这些组进行比较，生成 Kaplan-Meier 生存分析、差异表达基因 (DEGs) 和识别差异丰度微生物群落签名。净化分析精炼了签名列表，并通过多重线性回归建模和 Cox 比例风险模型验证了其作为独立预后指标的有效性。最后，对 DEGs 列表进行功能注释分析，以将数据联系在一起。共有 107 个属标记与患者生存显著相关（正相关或负相关），而两组患者的临床特征比较表明，上皮组织学在“高生存者”中更为常见，而双相型则主要出现于“低生存者”中。在 107 个属中，有 27 种已经与癌症相关的文章，而只有一种 (克雷伯菌) 与 MMe 相关的已发表文章。对两组之间的 DEGs 进行功能注释分析，显示脂肪酸代谢在“高生存者”中是最丰富的术语，而对于“低生存者”，丰富的术语主要与细胞周期/分裂相关。将这些思想和发现联系起来的是微生物群落影响，也受到脂质代谢的影响。最后，为了验证微生物群落的独立预后价值，采用了多重线性回归建模和 Cox 比例风险模型，并且两种方法都表明微生物群落是比病人年龄或癌症阶段更好的预后指标。本文所提出的发现，以及仅有的几篇广泛搜索验证属的有限文献，都突显了微生物和微生物群落作为一种潜在的基础分析和预后价值的丰富源泉。需要进行进一步的体外研究以阐明可能导致改变存活的分子机制和功能链接。版权所有©2023 Pentimalli、Krstic-Demonacos、Costa、Mutti 和 Bakker。

Despite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe.TCGA data on 86 MMe patients from cBioPortal underwent bespoke analysis. Median overall survival was used to divide patients into "Low Survivors" and "High Survivors". Comparison of these groups generated Kaplan-Meier survival analysis, differentially expressed genes (DEGs), and identification of differentially abundant microbiome signatures. Decontamination analysis refined the list of signatures, which were validated as an independent prognostic indicator through multiple linear regression modelling and Cox proportional hazards modelling. Finally, functional annotation analysis on the list of DEGs was performed to link the data together.107 genera signatures were significantly associated with patient survival (positively or negatively), whilst clinical characteristic comparison between the two groups demonstrated that epithelioid histology was more common in "High Survivors" versus biphasic in "Low Survivors". Of the 107 genera, 27 had published articles related to cancer, whilst only one (Klebsiella) had MMe-related published articles. Functional annotation analysis of the DEGs between the two groups highlighted fatty acid metabolism as the most enriched term in "High Survivors", whilst for "Low Survivors" the enriched terms primarily related to cell cycle/division. Linking these ideas and findings together is that the microbiome influences, and is influenced by, lipid metabolism. Finally, to validate the independent prognostic value of the microbiome, multiple linear regression modelling as well as Cox proportional hazards modelling were employed, with both approaches demonstrating that the microbiome was a better prognostic indicator than patient age or stage of the cancer.The findings presented herein, alongside the very limited literature from scoping searches to validate the genera, highlight the microbiome and microbiota as a potentially rich source of fundamental analysis and prognostic value. Further in vitro studies are needed to elucidate the molecular mechanisms and functional links that may lead to altered survival.Copyright © 2023 Pentimalli, Krstic-Demonacos, Costa, Mutti and Bakker.