Gut metagenomes, NSCLC patients, immunotherapy outcome, Paris

Over the past decade, accumulating evidence pointed to the clinical impact of the</p><p>intestinal microbiota on immunotherapeutic outcomes across various cancers. Although</p><p>specific gut microbial species have been associated with beneficial responses in meta-</p><p>analyses, no consensus exists on a gut microbiome signature for personalized prediction</p><p>of immunoresistance in clinical practice. Based on fecal shotgun metagenomics (MG)</p><p>sequencing data from a retrospective discovery cohort of 245 patients with advanced non-</p><p>small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI), we</p><p>constructed species-level co-abundance networks that were clustered into species</p><p>interacting groups (SIG) correlating with overall survival. Thirty-seven and forty-five</p><p>metagenomic species (MGS) belonged to clusters associated with resistance (SIG1) and</p><p>response (SIG2) to ICI, respectively. For each patient, we calculated the SIG1-SIG2 ratio</p><p>and integrated the trichotomic relative abundance of Akkermansia muciniphila (Akk)</p><p>when this ratio was poorly discriminant, to obtain a final TOPOSCORE, associated</p><p>with clinical outcome in a validation cohort of 254 NSCLC patients and in a third cohort</p><p>of 216 renal and urothelial carcinoma amenable to ICI. The TOPOSCORE outperformed</p><p>PD-L1 tumor scoring. Finally, the 83 MGS-based TOPOSCORE was translated into a 21</p><p>bacterial probe set qPCR-based scoring that was validated in a prospective cohort of</p><p>NSCLC. Custom scoring of intestinal bacteria by the TOPOSCORE could represent a</p><p>dynamic diagnosis tool of gut dysbiosis, that stratifies patients for microbiota-related</p><p>interventions.

Classified as human gut / stool shotgun DNA metagenome of adult and elderly by sonnet_x2 with confidence 0.68. Assay shotgun_dna.

• host run.host_tax_id · “9606”
• body site study.description · “fecal shotgun metagenomics (MG)”
• life stage study.description · “245 patients with advanced non-small cell lung cancer”
• life stage sample.attr.host_age · “69 (n=246/499)”

499 runs over 499 samples · mean 3.18 Gbp per run (median 3.17 Gbp, total 1,584.77 Gbp; 499 runs with a base count) · layout SINGLE 499 · platform ION_TORRENT 499 · models Ion Torrent S5 XL (499) · 0% of runs with a Sandpiper profile · first public 2024-06-05 – 2024-06-30

Zhang L first · Zhou DD · Feng J · Liao ZJ · Shu XL · Yang RM · Gao YC · Zhou HH · Zhang W · Zou Y · Liu R last · Jiang Y first · Che L · Li SC last · Yu K first · Sun X · Ma W · Yang J · Liu Y · Ren T · Wang Q · Wang J · Li X · Peng X · Yang L · Lv J · Yao Z · Zhang ZS

PRJNA1023797.csv.gz (16.3 KB) · parquet (93.7 KB) — all 499 samples, every field with route and confidence · PRJNA1023797_determinations.csv.gz (37.7 KB) — 5,475 evidence rows