Yuan Xuelian, Wang Zhina, Li Changjun, Lv Kebo, Tian Geng, Tang Min, Ji Lei, Yang Jialiang
School of Mathematical Sciences, Ocean University of China, Qingdao, China.
Department of Respiratory and Critical Care, Emergency General Hospital, Beijing, China.
Front Microbiol. 2022 Sep 16;13:1007831. doi: 10.3389/fmicb.2022.1007831. eCollection 2022.
Local recurrence and distant metastasis are the main causes of death in patients with lung cancer. Multiple studies have described the recurrence or metastasis of lung cancer at the genetic level. However, association between the microbiome of lung cancer tissue and recurrence or metastasis remains to be discovered. Here, we aimed to identify the bacterial biomarkers capable of distinguishing patients with lung cancer from recurrence or metastasis, and how it related to the severity of patients with lung cancer.
We applied microbiome pipeline to bacterial communities of 134 non-recurrence and non-metastasis (non-RM) and 174 recurrence or metastasis (RM) samples downloaded from The Cancer Genome Atlas (TCGA). Co-occurrence network was built to explore the bacterial interactions in lung cancer tissue of RM and non-RM. Finally, the Kaplan-Meier survival analysis was used to evaluate the association between bacterial biomarkers and patient survival.
Compared with non-RM, the bacterial community of RM had lower richness and higher Bray-Curtis dissimilarity index. Interestingly, the co-occurrence network of non-RM was more complex than RM. The top 500 genera in relative abundance obtained an area under the curve (AUC) of 0.72 when discriminating between RM and non-RM. There were significant differences in the relative abundances of , and , and so on between RM and non-RM. These biomarkers played a role in predicting the survival of lung cancer patients and were significantly associated with lung cancer stage.
This study provides the first evidence for the prediction of lung cancer recurrence or metastasis by bacteria in lung cancer tissue. Our results highlights that bacterial biomarkers that distinguish RM and non-RM are also associated with patient survival and disease severity.
局部复发和远处转移是肺癌患者死亡的主要原因。多项研究在基因水平上描述了肺癌的复发或转移。然而,肺癌组织微生物群与复发或转移之间的关联仍有待发现。在此,我们旨在鉴定能够区分肺癌复发或转移患者的细菌生物标志物,以及它与肺癌患者病情严重程度的关系。
我们将微生物组分析流程应用于从癌症基因组图谱(TCGA)下载的134例无复发和无转移(非RM)以及174例复发或转移(RM)样本的细菌群落。构建共现网络以探索RM和非RM肺癌组织中的细菌相互作用。最后,使用Kaplan-Meier生存分析来评估细菌生物标志物与患者生存之间的关联。
与非RM相比,RM的细菌群落丰富度较低,Bray-Curtis差异指数较高。有趣的是,非RM的共现网络比RM更复杂。相对丰度排名前500的属在区分RM和非RM时曲线下面积(AUC)为0.72。RM和非RM之间在 、 和 等的相对丰度上存在显著差异。这些生物标志物在预测肺癌患者生存方面发挥作用,并且与肺癌分期显著相关。
本研究为通过肺癌组织中的细菌预测肺癌复发或转移提供了首个证据。我们的结果表明,区分RM和非RM的细菌生物标志物也与患者生存和疾病严重程度相关。