正常组织对于研究疾病特异性差异基因表达至关重要。然而，健康的人类对照通常只能在尸检/解剖中获得。在癌症研究中，通常使用肿瘤附近的病理正常组织片段作为对照。然而，癌症如何系统性地影响相邻组织的基因表达在很大程度上尚未被深入研究。在本研究中，我们对实体肿瘤相邻组织和解剖获取的“健康”正常组织的分子特征进行了全面的跨癌症比较。我们发现了一系列与免疫细胞的激活、细胞内转运和自噬、细胞呼吸、端粒酶激活、p38信号转导、细胞骨架重塑和细胞外基质重构相关的系统分子差异。与此同时，肿瘤附近组织在凋亡信号和G2/M细胞周期转换检查点等负调节细胞生长的方面存在缺陷。我们还检测到了化学感知网络的广泛重排。在肿瘤附近正常组织中，有32种癌症药物的分子靶点过度或欠表达。这些过程可能由癌症和相邻正常组织之间相关的分子事件驱动，主要涉及炎症和调节细胞内分子通路，如p38、MAPK、Notch和IGF1信号转导。然而，我们通过猕猴尸检组织的模型表明，在4°C下的30分钟至24小时时间范围内，肺生物样本中的RNA降解模式会导致1140个基因的人为“差异”表达谱，尽管在肝脏中无法检测到差异。因此，这些问题应该在实践中得到解决。© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived "healthy" normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact "differential" expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.