Figure 2 from Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small Cell Lung Cancer
Year: 2026
Type: other
Abstract: Molecular features associated with sensitivity to KIF18A inhibition in SCLC. A, Scatter plot showing the KIF18A mRNA expression and NE status across SCLC cell lines. NE scores were calculated according to Zhang and colleagues (26) using a 50-gene NE signature. Each datapoint represents an individual SCLC cell line. B, Bar graph showing relative KIF18A mRNA levels across SCLC cell lines as measured by quantitative RT-PCR. Expression was normalized to GAPDH. Data represent mean ± SD from three independent biological replicates. C, Western blot analysis of KIF18A protein levels across a panel of SCLC cell lines. α-Tubulin was used as the loading control. Bar graph showing relative KIF18A protein levels across SCLC cell lines as measured by immunoblotting. Protein expression was normalized to α-tubulin. Data represent mean ± SD from three independent biological replicates. D, Dose–response curves showing the sensitivity of SCLC cell lines to a KIF18A inhibitor, generated using technical replicates. Cell lines were grouped by drug response at the highest tested concentration: sensitive if viability was <50%, resistant if viability was ≥85% (Imax_obs < 15%), and partial/excluded if viability remained ≥50% despite measurable inhibition (Imax_obs ≥ 10%–15%). E, Dot plots showing KIF18A transcript levels for individual SCLC cell lines classified as KIF18A inhibitor sensitive or resistant. F, Dot plots showing NE scores for individual SCLC cell lines classified as KIF18A inhibitor sensitive or resistant. G, Dot plots showing KIF18A protein levels for individual SCLC cell lines classified as KIF18A inhibitor sensitive or resistant. H, Summary of GSEA comparing transcriptomic profiles of AM-9022–sensitive (n = 4) vs. –resistant (n = 10) SCLC cell lines. Gene sets with positive normalized enrichment scores (NES; red) are enriched in AM-9022–sensitive SCLC cell lines, whereas gene sets with negative NES (black) are enriched in resistant cell lines and depleted in sensitive cell lines. I, GSEA enrichment score plots showing enrichment of CIN (CES), mitotic spindle, and spindle checkpoint in AM-9022–sensitive SCLC cell lines relative to resistant cell lines. Statistical significance was determined using the Mann–Whitney U test. DN, downregulated; Imax_obs, observed maximum inhibition; Neg, negative; ns, not statistically significant; Pos, positive.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W7211996144