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Table · dataset · 2026

Table 1_Integrated single-cell and multi-cohort analyses reveal CTCF as a key regulator of chemo-immunotherapy resistance in lung adenocarcinoma.docx

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Background<p>Chemo-immunotherapy has improved clinical outcomes in non-small cell lung cancer (NSCLC), but resistance remains a major challenge.

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The tumor cell states and molecular mechanisms underlying treatment resistance are not fully understood.</p>Methods<p>Single-cell RNA sequencing data from NSCLC patients receiving chemo-immunotherapy were integrated with public transcriptomic cohorts and functional experiments.

Resistance-associated tumor cell populations were identified, and key regulatory factors were investigated through bioinformatic analyses and experimental validation.</p>Results<p>Single-cell analysis identified a malignant epithelial cell subpopulation enriched in patients with stable disease, suggesting a resistance-associated tumor cell state. Genes derived from this population were associated with unfavorable prognosis and were used to construct a prognostic model with consistent performance across multiple independent cohorts.

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Among the candidate genes, CTCF was identified as a key regulator associated with poor survival and reduced immune infiltration. In an orthotopic lung tumor model, Ctcf knockdown enhanced the antitumor efficacy of pemetrexed combined with anti-PD-1 treatment and promoted CD8<sup>+</sup> T-cell activity. Mechanistically, CTCF directly upregulated RRM2 and CD276, which mediated chemotherapy resistance and immune suppression, respectively.</p>Conclusion<p>Our findings identify CTCF as a critical regulator of chemo-immunotherapy resistance in NSCLC.

The CTCF–RRM2/CD276 axis links tumor-intrinsic drug resistance with immune evasion and may represent a potential therapeutic target.</p>

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Cancer 75% · Disease 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75% · Tabular 65%
Provenance · 1 source records, 23 field assertions
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