Gut microbiota profiling and clinical response in patients with metastatic non-small cell lung cancer receiving endothelial growth factor-tyrosine kinase inhibitors (EGFR-TKI).

Abstract

e21050 Background: Pre-clinical mouse models have suggested that gut microbiota in immune relates with inflammation and modulates tumor response, while it remains uncertain in lung cancer patients with EGFR mutation. We aimed to evaluate the relationship between gut microbiota and early tumor response after EGFR-TKI treatment in metastatic non-small cell lung cancer (NSCLC) patients. Methods: NSCLC patients haboring EGFR exon 19del or 21L858R mutation were enrolled in this study in Tongji Hospital, Wuhan, China. Early response was assessed at 12 weeks after EGFR-TKI initiation per RECIST 1.1, and patients were categorized as responders (CR+PR) and non-responders (SD+PD). Stool sample was collected prior to EGFR-TKI treatment. The V3–V4 region of the 16S rRNA gene was amplified for the characterization of the gut microbiota profiling. Data were analyzed on the online tool of Majorbio Cloud Platform to compare microbiota community structure and abundance at α- and β-diversity levels. Linear discriminant analysis with effect size (LEfSe) was used to to identify biomarkers using a taxonomic bar chart. PICRUSt2 was used to predict the functional profiling of microbial communities. P-values < 0.05 were considered statistically significant. Results: From June 2020 to Sep 2022, 24 patients were included. CR, PR, SD and PD were recorded in 2 (8.3%), 14(58.3%), 6(25%) and 2(8.3%) patients, respectively. The four most abundant bacteria at phylum level were Firmicutes (64.4%), Bacteroidota (15.1%), Proteobacteria(14.7%), and Actinobacteriota (4.6%). The relative abundance of Actinobacteriota counts were significantly higher in responders than those with no-responders ( p= 0.032). There was a significant difference in the Sob index (α-diversity) between responders and no-responders (60.062 vs. 86.250, p= 0.043). β-diversity was similar between the two groups ( p= 0.087). Differential analysis using LEfSe identified that genus Rothia was significantly enriched in responders; phyla Actinobacteria and Deinococcota, genera Ruminococcus, Collinsella, Holdemanella were significantly enriched in non-responders. PICRUSt2 based on KEGG prediction identified that Transketolase and Carbamoyl-phosphate synthase were significantly enriched enzymes in non-responders compared with responders, the p values were 0.019 and 0.022, respectively. Conclusions: The early response of EGFR-TKI was associated with alteration of specific genera and metabolic function of gut microbiota. Further research with larger cohorts is needed to validate this pilot study. [Table: see text]