PO.CL01.12 · 临床研究
Profiling colon cancer architecture with spatial transcriptomics identifies clinically relevant stromal ecotypes
作者与单位
摘要 Abstract
Despite progress in the understanding of intra-tumor heterogeneity in colon cancer, the spatial organization of the cell types and states that compose colon tumors remains to be fully delineated. We constructed a large spatial transcriptomic atlas of 48 stage III colon cancers and identified recurrent, biologically relevant spatial ecosystems, including tumor and stromal ecotypes. Analysis of recurrence-associated profiles revealed a stromal-specific upregulation of a set of genes that includes the regenerative/revival-stem cell (REC/RSC) marker ANXA1 . Disease recurrence was accompanied by stromal-specific enrichment of REC/RSC and YAP activation signatures, together with increased associations between levels of ANXA1 and those of collagen-expressing genes. Dissection of the stromal compartment uncovered hidden heterogeneity and sub-cluster-specific enrichment in ANXA1 and related markers in patients with relapse. Further profiling at single cell resolution with Visium HD allowed spotting ANXA1 -expressing tumor cells within an environment marked by abundant collagen-producing cancer-associated fibroblasts (CAFs). Finally, we translated these findings to bulk transcriptomics by performing univariate and multivariate analyses and demonstrated the prognostic value of gene signatures derived from the spatial ecotypes and stromal sub-clusters across three independent cohorts comprising >3,500 stage II and stage III colon cancer patients. By mapping cellular ecosystems in localized colon cancer, this work lays the foundation to elucidate mechanisms of disease recurrence and inform therapeutic strategies. The validation of the spatially-derived prognostic signatures in bulk transcriptomic data paves the way for their potential integration into clinical practice to improve patient stratification.
利益披露 Disclosure
A. Cazelles, None..
C. Pilati, None..
D. Le Corre, None..
G. Cabrejas, None..
M. Sroussi, None..
C. Mulot, None..
C. Gallois, None..
G. Manceau, None..
M. Karoui, None..
I. Hernández-Verdin, None..
A. Bougoüin, None..
W. Fridman, None..
A. de Reyniès, None.
C. Lepage,
Novartis Other, Advisory.
AAA Other, Advisory.
AMGEN Other, Speaker fees.
Bayer Other, Speaker fees.
T. Andre,
Aptitude health Other, Consulting.
Abbvie Other, Consulting.
Biocartis Other, Consulting.
BMS Travel, Other, Consulting and lecture fees.
Gritstone Bio Other, Consulting.
GSK Other, Consulting and lecture fees.
MSD Oncology Travel, Other, Consulting and lecture fees.
Medicenna Other, Consulting.
Nimbus Other, Consulting.
Nordic Bioscience Other, Consulting.
Sanofi Other, Consulting and lecture fees.
Servier Other, Consulting and lecture fees.
Pfizer Other, Consulting.
Takeda/Lundbeck Other, Consulting.
Merck Serono Other, Lecture fees.
Roche/Genentech Other, Lecture fees.
Seagen Other, Lecture fees.
Inspirna Other, DMC member role.
J. Emile, None..
T. Z. Hirsch, None.
J. Taieb,
AMGEN Other, Consultancy and speaker fees.
Astellas Other, Consultancy and speaker fees.
BMS Other, Consultancy and speaker fees.
Merck Travel, Other, Consultancy and speaker fees.
MSD Other, Consultancy and speaker fees.
Novartis ), Other, Consultancy and speaker fees.
Pfizer Other, Consultancy.
Pierre Fabre ), Travel, Other, Consultancy and speaker fees.
Rottapharm Other, Consultancy.
Sanofi Other, Consultancy.
Servier ), Travel, Other, Consultancy and speaker fees.
Takeda Travel, Other, Consultancy and speaker fees.
Natera ), Other, Speaker fees.
P. Laurent-Puig,
AMGEN Other, Advisory or speaker fees.
Servier Other, Advisory or speaker fees.
Pierre Fabre Other, Advisory or speaker fees.
Biocartis Advisory or speaker fees.
Methys DX Stock.
S. Mouillet-Richard, None.