Authors
Lailing Li, Dandan Han, Xiaoliang Zhang, Hui Zhou, Jiajun Li, Tian Tian, Rubing Bai, Ke Xu, Yehong Xu, Cheng He, Linjuan Xu, Hao Wang, Hao Tang, Song Wei, Jun Li, Rui He, Shicheng Niu, Xi Gao, Fufeng Wang, Qifan Jing, Jiani Yin, Ling Xu, Lingling Xu, Zhi-Hong Zhang
Published in
MedComm. Volume 7. Issue 7. Pages e70846. Epub Jul 06, 2026.
Abstract
Combined immune checkpoint inhibitor (ICI) and chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, reliable biomarkers predictive of clinical benefit are lacking. We analyzed 54 patients with advanced NSCLC treated first-line with ICI plus chemotherapy. Pretreatment tumor biopsies underwent targeted DNA and RNA-seq. Plasma samples for circulating tumor DNA (ctDNA) profiling were collected at multiple timepoints. Associations between genomic, transcriptomic, and ctDNA features and objective response rate (ORR) and progression-free survival (PFS) were assessed. Genomic analysis revealed that LRP1B mutations predicted longer PFS (HR = 0.35, p = 0.034), whereas FBXW7 mutations were associated with shorter PFS (HR = 5.39, p = 0.001). Exploratory transcriptomic analysis identified high SPP1 and LHCGR expression as predictors of poor prognosis, while high IL24 expression correlated with longer PFS. CD8+ effector memory T-cell infiltration was significantly higher in responders (p = 0.029). Longitudinal ctDNA analysis showed that positivity at C2D1 (HR = 5.18, p = 0.004), C3D1 (HR = 17.81, p < 0.001), and C4D1(HR = 3.91, p = 0.018) was associated with inferior PFS. This multi-omics analysis highlights the potential of integrating genomic, transcriptomic, and ctDNA biomarkers to optimize immunotherapy strategies in NSCLC.
PMID:
42415854
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.
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