DNA-damaging agents include first-line drugs such as platinum (cisplatin, carboplatin), topoisomerase inhibitors (etoposide, doxorubicin), and replication inhibitors (cytarabine, gemcitabine). Despite their wide and long usage, there is no clinically available biomarker to predict responses to these drugs. Schlafen 11 (SLFN11), a putative DNA/RNA helicase, recently emerged as a dominant determinant of sensitivity to these drugs by enforcing the replication block in response to DNA damage. Since the clinical importance of SLFN11 is implicated, a comprehensive analysis of SLFN11 expression across human organs will provide a practical resource to develop the utility of SLFN11 in the clinic. In this study, we established a scoring system of SLFN11 expression by immunohistochemistry (IHC) and assessed SLFN11 expression in ~ 700 malignant as well as the adjacent non-tumor tissues across 16 major human adult organs. We found that the SLFN11 expression is tissue specific and varies during tumorigenesis. Although The Cancer Genome Atlas (TCGA) is a prevailing tool to assess gene expression in various malignant and normal tissues, our IHC data exhibited obvious discrepancy from the TCGA data in several organs. Importantly, SLFN11-negative tumors, potentially non-responders to DNA-damaging agents, were largely overrated in TCGA because TCGA samples are a mixture of infiltrating immune cells, including T cells, B cells, and macrophages, which have strong SLFN11 expression. Thus, our study reveals the significance of immunohistochemical procedures for evaluating expression of SLFN11 in patient samples and provides a robust resource of SLFN11 expression across adult human organs.

DNA 损伤剂包括一线药物，例如铂（顺铂、卡铂）、拓扑异构酶抑制剂（依托泊苷、多柔比星）和复制抑制剂（阿糖胞苷、吉西他滨）。尽管它们广泛且长期使用，但没有临床可用的生物标志物来预测对这些药物的反应。Schlafen 11 (SLFN11) 是一种推定的 DNA/RNA 解旋酶，最近通过强制复制阻断以响应 DNA 损伤，成为对这些药物敏感性的主要决定因素。由于涉及 SLFN11 的临床重要性，对 SLFN11 在人体器官中的表达进行综合分析将为开发 SLFN11 在临床中的效用提供实用资源。在这项研究中，我们通过免疫组织化学 (IHC) 建立了 SLFN11 表达评分系统，并评估了 16 个主要人类成人器官中约 700 个恶性组织和邻近非肿瘤组织中的 SLFN11 表达。我们发现 SLFN11 表达是组织特异性的，并且在肿瘤发生过程中会发生变化。尽管癌症基因组图谱 (TCGA) 是评估各种恶性和正常组织中基因表达的流行工具，但我们的 IHC 数据与几个器官中的 TCGA 数据存在明显差异。重要的是，SLFN11 阴性肿瘤，可能对 DNA 损伤剂无反应，在 TCGA 中被大大高估了，因为 TCGA 样本是浸润性免疫细胞的混合物，包括具有强 SLFN11 表达的 T 细胞、B 细胞和巨噬细胞。因此，