Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to HIV and population aging. Diffuse Large B-cell lymphoma (DLBCL), the most common lymphoma in SSA and worldwide, is highly associated with HIV, but molecular studies of HIV-associated DLBCL are scarce globally. We describe profiling of DLBCL from Malawi, aiming to elucidate tumor biology and identify clinically meaningful biomarkers specifically for SSA. Between June 1, 2013 and June 1, 2016, 59 cases of DLBCL (32 HIV+/27 HIV-) enrolled in the Kamuzu Central Hospital Lymphoma Study were characterized, of which 54 (92%) were negative for Epstein-Barr virus. Gene expression profiling (GEP) by whole transcriptome sequencing was performed on the first 36 cases (22 HIV+/14 HIV-). Immunohistochemistry (IHC) and GEP results were compared with published data and correlated to clinical outcome and pathologic features. Unsupervised clustering strongly segregated DLBCL by HIV status (p = 0.0003, Chi-squared test), indicating a marked contribution of HIV to expression phenotype. Pathway analysis identified that HIV-associated tumors were enriched in hypoxia, oxidative stress, and metabolism related gene expression patterns. Cell-of-origin subtype, determined by sequencing and IHC, did not associate with differences in overall survival (OS), while Ki-67 proliferation index ≥80% was associated with inferior OS in HIV+ DLBCL only (p = 0.03) and cMYC/BCL2 co-expression by IHC was negatively prognostic across the entire cohort (p = 0.01). This study provides among the first molecular characterizations of DLBCL from SSA, demonstrates marked gene expression differences by HIV status, and identifies genomic and immunophenotypic characteristics that can inform future basic and clinical investigations.

中文翻译：

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识别转录谱并评估马拉维 HIV 相关弥漫性大 B 细胞淋巴瘤的预后生物标志物。

由于艾滋病毒和人口老龄化，撒哈拉以南非洲 (SSA) 的淋巴瘤发病率正在上升。弥漫性大 B 细胞淋巴瘤 (DLBCL) 是 SSA 和全世界最常见的淋巴瘤，与 HIV 高度相关，但全球范围内对 HIV 相关 DLBCL 的分子研究很少。我们描述了来自马拉维的 DLBCL 的分析，旨在阐明肿瘤生物学并确定专门针对 SSA 的具有临床意义的生物标志物。在 2013 年 6 月 1 日至 2016 年 6 月 1 日期间，Kamuzu 中心医院淋巴瘤研究中纳入的 59 例 DLBCL（32 例 HIV+/27 例 HIV-）被特征化，其中 54 例 (92%) 的 Epstein-Barr 病毒呈阴性。对前 36 例（22 例 HIV+/14 例 HIV-）进行全转录组测序的基因表达谱分析 (GEP)。将免疫组织化学 (IHC) 和 GEP 结果与已发表的数据进行比较，并将其与临床结果和病理特征相关联。无监督聚类根据 HIV 状态强烈分离 DLBCL（p = 0.0003，卡方检验），表明 HIV 对表达表型的显着贡献。通路分析发现，HIV 相关肿瘤富含缺氧、氧化应激和代谢相关基因表达模式。通过测序和 IHC 确定的细胞源亚型与总生存期 (OS) 的差异无关，而 Ki-67 增殖指数≥80% 仅与 HIV+ DLBCL (p = 0.03) 和 cMYC 中的较差 OS 相关IHC 的 /BCL2 共表达在整个队列中具有负面预后意义 (p = 0.01)。这项研究提供了来自 SSA 的 DLBCL 的第一个分子特征，