低 CCL19 表达与接受化疗免疫治疗的滤泡性淋巴瘤患者的不良临床结局相关。
Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy.
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 41 Damucang Hutong, Xicheng District, Beijing, 100032, China.
出版信息
J Transl Med. 2021 Sep 20;19(1):399. doi: 10.1186/s12967-021-03078-9.
BACKGROUND
This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy.
METHOD
RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis.
RESULTS
A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25-0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells.
CONCLUSION
CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.
背景
本研究旨在识别与接受一线利妥昔单抗联合化疗治疗滤泡性淋巴瘤（FL）患者预后相关的关键基因。
方法
纳入数据集 GSE65135（n=24）的 RNA 测序数据进行差异表达基因（DEGs）分析。应用加权基因共表达网络分析（WGCNA）探索共表达网络并识别关键基因。分别通过分析 GSE119214 数据集（n=137）和中国医学科学院肿瘤医院与北京协和医学院独立患者队列（n=32）的 RNAseq 表达数据和 ELISA 定量的血清蛋白浓度，验证关键基因的表达和预后。进行基因集富集分析（GSEA）、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。应用 CIBERSORT 进行肿瘤浸润免疫细胞（TIICs）亚群分析。
结果
共获得 3260 个 DEGs，其中 1861 个基因上调，1399 个基因下调。通过 WGCNA，鉴定出 8 个关键基因 PLA2G2D、MMP9、PTGDS、CCL19、NFIB、YAP1、RGL1 和 TIMP3。Kaplan-Meier 分析和多变量 COX 回归分析表明，CCL19 独立与接受利妥昔单抗和化疗治疗的 FL 患者的总生存（OS）相关（HR=0.47，95%CI [0.25-0.86]，p=0.014）。更高的血清 CCL19 浓度与更长的无进展生存期（PFS，p=0.014）和 OS（p=0.039）相关。TIICs 亚群分析表明，CCL19 表达与单核细胞和巨噬细胞 M1 呈正相关，与幼稚 B 细胞和浆细胞呈负相关。
结论
CCL19 的表达与生存结果相关，可能是接受一线化疗免疫治疗的 FL 的潜在预后生物标志物。
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