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<p>Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are highly effective against EGFR-mutant non-small cell lung cancer (NSCLC); however, identifying biomarkers that predict prognosis and adverse events is necessary. Although the gut microbiota is considered to be a biomarker for NSCLC without mutations, no studies have examined its potential as a biomarker for EGFR-mutant NSCLC. Here, we investigated the association between gut microbiota composition and diarrhea, a common side effect caused by EGFR-TKIs. In addition, we examined the association between the efficacy of EGFR-TKIs and the gut microbiota. A total of&#xa0;21 NSCLC patients with EGFR mutations were enrolled. Fecal samples were collected prior to EGFR-TKI treatment and 16S rRNA metagenome sequencing was performed to evaluate the microbiota profile. In addition, α-diversity, β-diversity, and Linear discriminant analysis Effect Size (LEfSe) analyses were performed. The α-diversity of the gut microbiota was higher in patients with grade 0–1 diarrhea than in those with grade 2–3 diarrhea (Shannon, <i>p</i> = 0.0367). In terms of β-diversity, there was a significant difference in the best overall response between patients with a partial response (PR) to EGFR-TKIs and those with stable disease (SD)/progressive disease (PD) (weighted <i>p</i> = 0.041). Analysis of microbial composition revealed an increased abundance of <i>Ruminococcus</i> in the PR group. In patients taking EGFR-TKIs, a higher α-diversity may be associated with less severe diarrhea. In addition, a high abundance of <i>Ruminococcus</i> may be a potential biomarker for predicting favorable efficacy of EGFR-TKIs.</p>

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The gut microbiota as a potential biomarker in patients with EGFR-mutant lung cancer

  • 期刊论文

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  • 发表日期：

    2025年12月11日

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  • Chiori Tabe,
  • Daisuke Motooka,
  • Toshitsugu Fujita,
  • Tomonori Makiguchi,
  • Kageaki Taima,
  • Hisashi Tanaka,
  • Masamichi Itoga,
  • Yoshiko Ishioka,
  • Takahiro Akita,
  • Mina Ishidoya,
  • Kei Chubachi,
  • Takashi Fukushima,
  • Yusuke Tanaka,
  • Haruka Odagiri,
  • Yuko Kameyama,
  • Yuri Kobori,
  • Sadatomo Tasaka,
  • Hodaka Fujii

摘要

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are highly effective against EGFR-mutant non-small cell lung cancer (NSCLC); however, identifying biomarkers that predict prognosis and adverse events is necessary. Although the gut microbiota is considered to be a biomarker for NSCLC without mutations, no studies have examined its potential as a biomarker for EGFR-mutant NSCLC. Here, we investigated the association between gut microbiota composition and diarrhea, a common side effect caused by EGFR-TKIs. In addition, we examined the association between the efficacy of EGFR-TKIs and the gut microbiota. A total of 21 NSCLC patients with EGFR mutations were enrolled. Fecal samples were collected prior to EGFR-TKI treatment and 16S rRNA metagenome sequencing was performed to evaluate the microbiota profile. In addition, α-diversity, β-diversity, and Linear discriminant analysis Effect Size (LEfSe) analyses were performed. The α-diversity of the gut microbiota was higher in patients with grade 0–1 diarrhea than in those with grade 2–3 diarrhea (Shannon, p = 0.0367). In terms of β-diversity, there was a significant difference in the best overall response between patients with a partial response (PR) to EGFR-TKIs and those with stable disease (SD)/progressive disease (PD) (weighted p = 0.041). Analysis of microbial composition revealed an increased abundance of Ruminococcus in the PR group. In patients taking EGFR-TKIs, a higher α-diversity may be associated with less severe diarrhea. In addition, a high abundance of Ruminococcus may be a potential biomarker for predicting favorable efficacy of EGFR-TKIs.