METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype.
RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy.
CONCLUSIONS: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.
方法:我们共纳入56例接受新辅助抗PD1治疗的OTSCC患者。单变量和多变量Cox回归分析,Kaplan-Meier生存分析,进行免疫组织化学染色。此外,我们获得了泛癌症样本的基因表达谱,并进行了GSEA和KEGG通路分析.此外,数据来自TCGA,MSigDB,UALCAN,利用GEPIA和TIMER构建FAMRGs亚型。
结果:我们的发现表明,高体重指数(BMI)与改善的PFS显着相关(HR=0.015;95%CI,0.001至0.477;p=0.015),可能归因于PD1+T细胞浸润增加。在用免疫疗法治疗的泛癌症患者中,在应答组和非应答组之间鉴定了总共91个差异表达的FAMRG。其中,6个集线器FAMRG(ACSL5,PLA2G2D,发现PROCA1,IL4I1,UBE2L6和PSME1)影响HNSCC中的PD-1表达和T细胞浸润,这可能会影响抗PD1治疗的疗效。
结论:本研究表明,肥胖可作为接受新辅助抗PD1治疗的OTSCC患者的可靠预后预测因子。此外,6个hubFAMRGs的表达(ACSL5,PLA2G2D,PROCA1,IL4I1,UBE2L6和PSME1)在抗PD1治疗中起着关键作用,值得进一步研究。