FIGURE 1 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
posted on 2023-09-29, 14:20authored byBoris 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
<p>BMP2 induces early transformation of a model of breast SCs and increases CD10 expression. <b>A,</b> Schematic representation of the experimental protocol used to obtain the MCF10-CT, MC26, and M1B26 cell lines from the MCF10A cells. <b>B,</b> Quantification of soft-agar colony formation [error bars represent the SD (<i>n =</i> 7), significance measured using the Mann–Whitney test is indicated on the graph by the <i>P</i> values. <i>ns for P ></i> 0.05]. <b>C,</b> Xenografts of the indicated number cells of MCF10A-derived models injected into nude mice presented as the number of successful grafts after 4 weeks/mouse (<i>n</i> = 10). <b>D,</b> GSEA of transcriptomic data comparing MC26 cells (top row) or M1B26 cells (bottom row) with MCF10A-CT cells. Data represent enrichment plots analyzed using public gene sets (<a href="#bib41" target="_blank">41</a>) of upregulated (left) or downregulated (right) genes in human primary ductal carcinoma compared with healthy tissues. <b>E,</b> GSEA of transcriptomic data comparing MC26 (first column) or M1B26 (second column) with CT cells and M1B26 with MC26 cells (third column). The “hallmarks” gene sets from the MSigDB were used and the NES (normalized enrichment score) with <i>P</i> values inferior to 0.05 are shown. <b>F,</b> E-CFC Progenitor content from MCF10A-CT cells (<i>n</i> = 5), MC26 cells (<i>n</i> = 8) or M1B26 cells (<i>n</i> = 6) quantified after 6 days by scoring colonies numbers and presented/10,000 cells. <b>G,</b> Number of spheres per 100 seeded cells after 1 week from MCF10A-CT cells (<i>n = 4</i>), MC26 cells (<i>n = 6</i>), and M1B26 cells (<i>n = 6</i>). <b>H,</b> TDLU, 3D structures from primary human breast cells (top) and MCF10A cell line (bottom). <b>I,</b> Images at day 21 of 3D structures in the TDLU assay from MCF10A-CT, MC26, or M1B26 cells. A representative TDLU section from MCF10A-CT, stained with H&E, is shown on the top right. <b>J,</b> Flow cytometry analysis of CD10 expression on MCF10A-CT (<i>n = 4</i>), MC26 (<i>n = 7</i>), and M1B26 (<i>n = 6</i>) presented as the percentage of positive cells (left) and mean fluorescence intensity (right).</p>
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
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.