Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J Natl Cancer Inst. 2023 Aug 8;115(8):989-993. doi: 10.1093/jnci/djad083.
Intratumoral microbes may have multifunctional roles in carcinogenesis. Microsatellite instability (MSI) is associated with higher tumor immunity and mutational burden. Using whole transcriptome and whole genome sequencing microbial abundance data, we investigated associations of intratumoral microbes with MSI, survival, and MSI-relevant tumor molecular characteristics across multiple cancer types including colorectal cancer (CRC), stomach adenocarcinoma, and endometrial carcinoma. Among 451 CRC patients, our key finding was strong associations of multiple CRC-associated genera, including Dialister and Casatella, with MSI. Dialister and Casatella abundance was associated with improved overall survival (hazard ratiomortality = 0.56, 95% confidence interval = 0.34 to 0.92, and hazard ratiomortality = 0.44, 95% confidence interval = 0.27 to 0.72), respectively, comparing higher relative to lower quantiles. Multiple intratumor microbes were associated with immune genes and tumor mutational burden. Diversity of oral cavity-originating microbes was also associated with MSI among CRC and stomach adenocarcinoma patients. Overall, our findings suggest the intratumor microbiota may differ by MSI status and play a role in influencing the tumor microenvironment.
肿瘤内微生物在癌症发生中可能具有多种功能。微卫星不稳定性 (MSI) 与更高的肿瘤免疫和突变负担相关。使用全转录组和全基因组测序微生物丰度数据，我们研究了肿瘤内微生物与 MSI、生存以及多种癌症类型（包括结直肠癌 (CRC)、胃腺癌和子宫内膜癌）中与 MSI 相关的肿瘤分子特征的相关性。在 451 名 CRC 患者中，我们的主要发现是多种与 CRC 相关的属，包括 Dialister 和 Casatella，与 MSI 强烈相关。Dialister 和 Casatella 的丰度与总体生存率提高相关（风险比死亡率=0.56，95%置信区间=0.34 至 0.92，风险比死亡率=0.44，95%置信区间=0.27 至 0.72），分别比较更高和更低的分位数。多个肿瘤内微生物与免疫基因和肿瘤突变负担相关。口腔起源的微生物多样性也与 CRC 和胃腺癌患者的 MSI 相关。总体而言，我们的研究结果表明，肿瘤内微生物群可能因 MSI 状态而异，并在影响肿瘤微环境中发挥作用。
