{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:32Z","timestamp":1785308432150,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung squamous cell carcinoma (LUSC) represents a predominant subtype of non-small cell lung cancer (NSCLC) with scarce effective targeted therapeutic options, rendering immune checkpoint inhibitor (ICI)-based regimens the standard first-line treatment for advanced-stage disease. Fibroblast growth factor receptor 1 (FGFR1) copy number (CN) gain is a prevalent genomic aberration in LUSC; nevertheless, the correlation between FGFR1 CN gain and ICI therapeutic efficacy has not yet been clarified. This retrospective single-center study aimed to explore the predictive value of FGFR1 CN gain in advanced LUSC patients receiving first-line ICI monotherapy or combination regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively enrolled 181 patients with stage IIIB\u2013IV advanced LUSC who received first-line ICI-based treatment at Shanghai Chest Hospital from January 2018 to July 2023. Next-generation sequencing (NGS) was performed to detect FGFR1 copy number status, and FGFR1 CN gain was defined as an estimated copy number &amp;gt; 2. Immunohistochemistry was applied to assess PD-L1 expression levels. Progression-free survival (PFS) was set as the primary endpoint, while secondary endpoints encompassed overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Multivariate Cox proportional hazards regression was utilized to identify independent prognostic predictors of PFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the total 181 participants, 44 patients (24.3%) harbored FGFR1 CN gain. Relative to patients without FGFR1 CN gain, the FGFR1 CN-gain cohort exhibited a significantly lower DCR (84.1% vs. 94.9%, P = 0.015) and shorter median PFS (7.7 months vs. 9.5 months, P = 0.025). No intergroup disparities in ORR or OS reached statistical significance. Multivariate Cox regression further validated that FGFR1 CN gain served as an independent unfavorable prognostic factor for shortened PFS (HR = 1.554, 95% CI: 1.077\u20132.242, P = 0.018).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>FGFR1 copy number gain is independently linked to inferior progression-free survival among patients with advanced LUSC undergoing first-line ICI-based treatment. FGFR1 CN gain holds promising potential as a predictive biomarker for suboptimal clinical outcomes in this patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1718660","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:02:57Z","timestamp":1785304977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["FGFR1 copy number gain is independently associated with shorter progression-free survival in advanced lung squamous cell carcinoma treated with first-line immune checkpoint inhibitor-based therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuya","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, 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