Tigecycline-induced coagulation gene prognostic prediction model and intestinal flora signature in AML

Front Immunol. 2024 Nov 14:15:1486592. doi: 10.3389/fimmu.2024.1486592. eCollection 2024.

Abstract

Infection is among the most common causes of death in patients with acute myeloid leukemia (AML) after chemotherapy. The anti-tumor effect of the intestinal microbiota in patients with AML is increasingly being recognized. Tigecycline, a broad-spectrum antibiotics, plays a vital role in the anti-infection treatment of AML patients with neutropenia and accompanying infections. Previously, this group reported that long-term use of tigecycline caused coagulation dysfunction in patients with hematological malignancies, increasing the risk of casualties. RNA sequencing was performed on CHO cells before and after tigecycline treatment. Further, the combined analysis of AML prognostic differentially expressed genes revealed 13 genes affected by tigecycline and closely related to AML prognosis. These genes were used for modeling analysis, and the results showed that the prepared model significantly improved the prognostic prediction efficiency for AML patients. The model also explored the correlation between prognosis score and immune cells infiltrating tumors and immune therapy targets. Moreover, 16S sequencing was performed on fecal samples from AML patients before and after tigecycline treatment. The results revealed that tigecycline significantly altered the distribution of intestinal microbiota in AML patients - These changes in microbiota are related to chemotherapy resistance. This study emphasizes the importance of intestinal microbiota in AML prognosis. Thus, the findings of this study show that the long-term use of antibiotics can not only cause dysbiosis of the intestinal microbiota but also indirectly affect the sensitivity of chemotherapy drugs, affecting the prognosis of AML patients.

Keywords: 16S sequencing; AML; intestinal microbiota; prognosis model; tigecycline.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Blood Coagulation / drug effects
  • Blood Coagulation / genetics
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Gastrointestinal Microbiome* / genetics
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / microbiology
  • Male
  • Middle Aged
  • Prognosis
  • Tigecycline* / therapeutic use

Substances

  • Tigecycline
  • Anti-Bacterial Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (Project #: 82201739 and 82000144), Shenzhen Science and Technology Program#: JCYJ20220530160214031, the General Program for Clinical Research at Peking University Shenzhen Hospital (No. LCYJ2021037), the Research Foundation of Peking University Shenzhen Hospital (No. JCYJ2021007) and Guangzhou Basic and Applied Basic Research Foundation (202201011458), Shenzhen Biomedical Industry Major Public Service Platform and Core Technology Research Special Support Plan (No. XMHT20220104048).