基于免疫抑制性Neu_2中性粒细胞亚群模型精准预测前列腺癌生存预后及免疫治疗应答

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A risk prediction model for prognosis and immunotherapy response in prostate cance1 patients based on immunosuppressive neutrophil Neu_2 subsets

CHENZixian，ZHOJiawei，ANLeiHUANGZipeng，XUEangyi，HENinku DepartmentofUrologyhirdAfiliatedHospitalofSouthernMedicalUniersity，Guangzhou5oCina

Abstract：Objective Toidentify immunosuppressive neutrohil subsets inpatients with prostatecancer （PCa）andconstructa riskpredictionmodelforprognosisandimmunotherapyresponseof thepatientsbasedonthese neutrophilsubsets.Methods Single-cellandtranscriptomedatafromPCapatientswerecollectedfromtheGeneExpressionOmnibus（GEO）andThe CancerGenome Atlas （TCGA）.Neutrophil subsetsinPCa were identified through unsupervisedclustering，andtheir biologicalfunctinsandeffectsonimmuneegulationwereaalyedbyfunctionaleichment，cellinteractionndped timeseriesanalyses.Lasso-Coxregresion wasutilizedtoconstructaprognosticriskmodelbasedontheimmunosuppressive neutrophil subsets，and survivalanalysisandROCcurve analysis were used tocomparethe prognosisof PCa patients with highand lowrisksstratified using this model.Therelationshipofthe prognosticriskmodel withPCaimmune infiltrationand immune response was evaluated using CIBERSORT and TIDE scores. Results PCa tisues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues （P<0.05） . PCa-associated neutrophils could be clustered intotwoindependentcellsubsets：Neu_1andNeu_2.Neu_2cels exhibitedhighlyenrichedimmunoregulatoryfunctiosand werehighlydereiatedndure，itregatediouppessieoinsschsF2d. BasedonthegeneticcharacteristicsofNeu_2cellsubsets，theprognosticriskmodelwasconstructed.Thepatientsinthehig risk group identified by themodel hada shorter biochemical recurrence time （P<0.05） andahigherproportionof Tregsand M2-TAMs cell infiltration （P<0.05） witha higher risk of immune rejection and poorer immune response scores. Conclusion PCa-associatedneutrophilsarehighlyheterogeneous.Theprognosticriskmodelconstructedbasedontheimmunosuppressive neutrophilNeu_2subsetcaneffctivelypredictboththesurvivaloutcomesandimmuneresponseofPCapatients. Keywords： single-cellRNA sequencing; transcriptomics; prostate cancer; neutrophils; tumor microenvironment

前列腺癌（PCa）作为男性高发恶性肿瘤，发病率随人口老龄化持续攀升2，其临床进展可划分为激素敏感型与去势抵抗型（mCRPC），后者转移性强且治疗难度显著增加。（剩余17180字）