Cellular secreted proteins (secretome), together with cellular membrane proteins, collectively referred to as secretory and membrane proteins (SMPs) are a large potential source of biomarkers as they can be used to indicate cell types and conditions. SMPs have been shown to be ideal candidates for several clinically approved drug regimens including for cancer. This study aimed at performing a functional analysis of SMPs within different cancer subtypes to provide great clinical targets for potential prognostic, diagnostic and the therapeutics use. Using an innovative majority decision-based algorithm and transcriptomic data spanning 5 cancer types and over 3000 samples, we quantified the relative difference in SMPs gene expression compared to normal adjacent tissue. A detailed deep data mining analysis revealed a consistent group of downregulated SMP isoforms, enriched in hematopoietic cell lineages (HCL), in multiple cancer types. HCL-associated genes were frequently downregulated in successive cancer stages and high expression was associated with good patient prognosis. In addition, we suggest a potential mechanism by which cancer cells suppress HCL signaling by reducing the expression of immune-related genes. Our data identified potential biomarkers for the cancer immunotherapy. We conclude that our approach may be applicable for the delineation of other types of cancer and illuminate specific targets for therapeutics and diagnostics.

中文翻译：

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利用生物信息学鉴定基于人类分泌组和膜蛋白质组的癌症生物标志物。

细胞分泌蛋白 (secretome) 与细胞膜蛋白一起统称为分泌蛋白和膜蛋白 (SMP)，它们是生物标志物的重要潜在来源，因为它们可用于指示细胞类型和条件。SMP 已被证明是几种临床批准的药物治疗方案的理想候选者，包括癌症治疗方案。本研究旨在对不同癌症亚型中的 SMP 进行功能分析，为潜在的预后、诊断和治疗用途提供重要的临床目标。使用创新的基于多数决策的算法和跨越 5 种癌症类型和 3000 多个样本的转录组数据，我们量化了 SMPs 基因表达与正常邻近组织相比的相对差异。详细的深度数据挖掘分析揭示了一组一致的下调 SMP 同种型，在多种癌症类型中富含造血细胞谱系 (HCL)。HCL 相关基因在连续的癌症阶段经常下调，高表达与良好的患者预后相关。此外，我们提出了癌细胞通过减少免疫相关基因表达来抑制 HCL 信号传导的潜在机制。我们的数据确定了癌症免疫疗法的潜在生物标志物。我们得出结论，我们的方法可能适用于描述其他类型的癌症，并阐明治疗和诊断的特定目标。HCL 相关基因在连续的癌症阶段经常下调，高表达与良好的患者预后相关。此外，我们提出了癌细胞通过减少免疫相关基因表达来抑制 HCL 信号传导的潜在机制。我们的数据确定了癌症免疫疗法的潜在生物标志物。我们得出结论，我们的方法可能适用于描述其他类型的癌症，并阐明治疗和诊断的特定目标。HCL 相关基因在连续的癌症阶段经常下调，高表达与良好的患者预后相关。此外，我们提出了癌细胞通过减少免疫相关基因表达来抑制 HCL 信号传导的潜在机制。我们的数据确定了癌症免疫疗法的潜在生物标志物。我们得出结论，我们的方法可能适用于描述其他类型的癌症，并阐明治疗和诊断的特定目标。