Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Lymphoma. Transcriptional Profiling Identifies Prognostic Gene Signatures for Conjunctival Lymphoma

This study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival lymphoma and identifies prognostically relevant biomarkers. 10 formalin-fixed and paraffin-embedded conjunctival lymphoma and 8 healthy conjunctival specimens were analyzed by MACE RNA sequencing. The 3,417 upregulated genes in conjunctival lymphoma were involved in processes such as B cell proliferation and Rac protein signaling, whereas the 1,188 downregulated genes contributed most significantly to oxidative phosphorylation and UV protection. The tumor microenvironment, as determined by deconvolution analysis, was mainly composed of multiple B cell subtypes which reflects the tumor’s B cell lineage. However, several T cell types, including T helper 2 cells and regulatory T cells, as well as innate immune cell types, such as anti-inflammatory macrophages and plasmacytoid dendrit-ic cells, were also strongly enriched in conjunctival lymphoma. A 13-biomarker prognostic panel, including S100A8 and S100A9, classified ocular and extraocular tumor recurrence, exceeded prognostic accuracy of Ann Arbor and AJCC staging, and demonstrated prognos-tic value for patient survival in 21 different cancer types in a database of 12,332 tumor pa-tients. These findings may lead to new options of targeted therapy and may improve prog-nostic prediction for conjunctival lymphoma. Overall design: MACE RNA sequencing of 10 conjunctival lymphoma and 8 healthy conjunctiva samples

本研究对结膜淋巴瘤的转录组特征及细胞肿瘤微环境进行了系统表征，并鉴定出与预后相关的生物标志物。本研究纳入10例福尔马林固定石蜡包埋（formalin-fixed and paraffin-embedded，FFPE）结膜淋巴瘤样本与8例健康结膜标本，采用MACE RNA测序进行分析。结膜淋巴瘤中上调的3417个基因主要参与B细胞增殖、Rac蛋白信号通路等生物学过程；而下调的1188个基因则显著富集于氧化磷酸化与紫外线防护相关通路。通过解卷积分析（deconvolution analysis）鉴定得到的肿瘤微环境，主要由多种B细胞亚型构成，这印证了该肿瘤的B细胞谱系起源。然而，多种T细胞亚型（包括辅助性T细胞2型（T helper 2 cells）与调节性T细胞）以及先天免疫细胞亚型（如抗炎性巨噬细胞与浆细胞样树突状细胞）同样在结膜淋巴瘤组织中显著富集。本研究构建了包含S100A8与S100A9在内的13基因预后标志物组合，该组合可有效区分眼内与眼外肿瘤复发，其预后准确性优于Ann Arbor分期与AJCC分期系统，并在包含12332例肿瘤患者的数据库中，对21种不同癌症类型的患者生存情况均展现出预后价值。上述研究结果可为结膜淋巴瘤的靶向治疗提供新的潜在策略，并有助于提升该疾病的预后预测效能。整体实验设计：对10例结膜淋巴瘤样本与8例健康结膜样本开展MACE RNA测序。