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FIGURE 2 from An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers

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posted on 2023-09-29, 14:20 authored by Boris Guyot, Flora Clément, Youenn Drouet, Xenia Schmidt, Sylvain Lefort, Emmanuel Delay, Isabelle Treilleux, Jean-Philippe Foy, Sandrine Jeanpierre, Emilie Thomas, Janice Kielbassa, Laurie Tonon, Helen He Zhu, Pierre Saintigny, Wei-Qiang Gao, Arnaud de la Fouchardiere, Franck Tirode, Alain Viari, Jean-Yves Blay, Véronique Maguer-Satta

The molecular identity of untransformed CD10-positive cells increase with mammary gland transformation. A, CD10 transcript expression in TCGA breast tumors according to the molecular classification compared with normal samples. B, Kaplan–Meier plot of patients with breast cancers in TCGA cohort as a function of CD10 expression level. C, Quantification in a TMA of the percentage of tumors with CD10 IHC staining higher than 20% according to tumor subtype. D, Kaplan–Meier plot of patients with breast cancers from the TMA (as in C) as a function of CD10 protein expression level. E, Schematic representation of the experimental protocol used to obtain identify the ENI10 molecular signature. F, ssGSEA quantification of the CD10 signature score in the different MCF10A-derived cell lines with nontransformed (CT, n = 6), early (MC26, n = 6) and more aggressive (M1B26, n = 8) transformed models. G, ssGSEA ENI10 score of human primary DCIS versus healthy mammary gland (series GSE21422). H, ssGSEA ENI10 score of matched normal or tumoral breast tissue from breast cancer subtypes from TCGA's Pan-Cancer Atlas. I, ssGSEA ENI10 score from RNA-seq transcriptomic data from three normal breast epithelial cells samples (wildtype) and six BRCA mutated healthy epithelial cells samples. J, Kaplan–Meier plots of patients with breast cancers in TCGA cohort as a function of cancer stage and ENI10 score. K, Using transcriptomic data from the “Genomics of drug sensitivity in cancer” project from the Sanger Institute, ENI10 score of human breast cancers cell lines were correlated with their IC50 to 441 drugs. Drugs showing a significative negative correlation between the ENI10 ssGSEA score and IC50 (indicating a sensitivity to the drug when the ENI10 score increase) are shown. According to the GDSC guidelines, red dots show drugs with a significative IC50 correlation with the ENI10 score with a P value inferior to 0.001 and a Benjamini–Hochberg FDR inferior to 0.25. Black dots show suggestive correlations with a P value inferior to 0.005 and a nonparametric P value inferior to 0.1.

Funding

Canceropole Rhone Auvergne

Agence Nationale de la Recherche (ANR)

Institut National Du Cancer (INCa)

Canceropole Ile de France

Region Rhone-Alpes

Ligue Nationale contre le Cancer

Fondation ARC pour la Recherche sur le Cancer (ARC)

Fondation MSD-Avenir

Dechaine ton coeur

Association Ruban Rose

Comite Feminin pour le Depistage du Cancer du Sein 74

History

ARTICLE ABSTRACT

We identified a molecular signature called ENI10 which, owing to its biological link with stem cell properties, predicts patient outcome and drugs efficiency in breast and several other cancers. ENI10 should allow early and optimized clinical management of a broad number of cancers, regardless of the stage of tumor progression.