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Abstract：
OBJECTIVE: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy.
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.
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.
摘要：
目的：以前的研究表明，肥胖可能会影响抗PD1治疗的疗效，但潜在的机制仍不清楚。在这项研究中,我们的目的是确定pembrolizumab治疗的口腔舌鳞状细胞癌(OTSCC)患者肥胖的预后价值,并建立基于脂肪酸代谢相关基因(FAMRGs)的免疫疗法亚型.
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。
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。
