{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:54:38Z","timestamp":1776315278347,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, and despite effective first-line immunochemotherapy a substantial proportion of patients develop relapse\/refractory (RR) disease, underscoring the need for practical biomarkers beyond clinical risk scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively evaluated FGR protein expression by immunohistochemistry (IHC) in 91 patients with\n                      <jats:italic>de novo<\/jats:italic>\n                      DLBCL treated with first-line R-CHOP. FGR staining was scored using an immunoreactive score (IRS), and high expression was defined as IRS \u2265 2. Associations with RR events and survival were assessed by Kaplan-Meier analysis and Cox regression, and predictive performance at 5 years was compared with the International Prognostic Index (IPI) using Receiver operating characteristic (ROC) analysis. External validation was performed using a publicly available gene-expression dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High FGR expression was observed in 64 of 91 tumors (70.3%) and was associated with a higher 5-year RR rate (29.7% vs 7.4%, P = 0.021). In Kaplan-Meier analyses, progression-free survival (PFS) was 69.1% in the high-expression group versus 92.1% in the low-expression group (P = 0.093), and overall survival (OS) was 80.0% versus 96.2% (P = 0.050); separation was more pronounced in the non-germinal center B-cell (non-GCB) subgroup. In multivariable Cox regression, high FGR remained independently associated with inferior 5-year PFS (HR 4.73, 95% CI 1.03-21.65; P = 0.045) and showed a strong trend toward inferior 5-year OS (HR 6.52, 95% CI 0.79-53.99; P = 0.082). ROC analysis suggested that FGR and IPI had similar discrimination at 5 years in this cohort. In external validation, FGR mRNA expression was elevated in non-GCB cases, and high FGR expression (upper quartile) was associated with a trend toward inferior OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Elevated FGR protein expression identifies a subset of DLBCL patients with increased treatment failure and inferior outcomes, particularly within non-GCB subtypes, supporting prospective validation in larger, less selected cohorts and further mechanistic studies of the FGR\/Src-family kinase axis as a candidate therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1688949","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:21:04Z","timestamp":1776313264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated FGR protein expression identifies a high-risk subset of diffuse large B-cell lymphoma and a potential therapeutic target"],"prefix":"10.3389","volume":"16","author":[{"given":"Kexin","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Peking University Institute of Hematology, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ailing","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Cellular and Genetic Medicine, School of Basic Medical 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