Time of day bias for biological sampling in studies of mammary cancer.

Time of day bias for biological sampling in studies of mammary cancer.
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DOI:
10.1038/s41598-023-50785-y
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发表时间:
2024-01-08
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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尽管其已被证明具有生物学意义,但一天中的时间在临床前和临床研究中却是一个被广泛忽视的生物学变量。一天中的时间如何影响周围肿瘤对中枢(大脑)功能的影响仍不清楚。因此,我们测试了这样的假设:外周乳腺癌肿瘤会改变大脑中免疫反应的转录组,并且这些反应会根据一天中的时间而变化。我们预测一天中不同时间的采样偏差会改变对结果的解释。使用 Nanostring nCounter 免疫面板对在中暗和中光条件下从携带乳腺肿瘤和注射载体的小鼠收集的脑组织进行分析。周围乳腺肿瘤显着影响了该组中 770 个基因中 100 多个独特基因在大脑内的表达,并且这些基因中只有不到 25% 在一天中受到类似影响。事实上,差异表达基因所代表的 65% 至 75% 的 GO 生物过程取决于一天中的采样时间。不能低估当日时间抽样偏差对研究解释的影响。我们鼓励在研究中将一天中的时间视为一个重要的生物变量,并对其进行适当控制,并在研究结果中清楚地报告一天中的时间。
Despite its demonstrated biological significance, time of day is a broadly overlooked biological variable in preclinical and clinical studies. How time of day affects the influence of peripheral tumors on central (brain) function remains unspecified. Thus, we tested the hypothesis that peripheral mammary cancer tumors alter the transcriptome of immune responses in the brain and that these responses vary based on time of day; we predicted that time of day sampling bias would alter the interpretation of the results. Brain tissues collected at mid dark and mid light from mammary tumor-bearing and vehicle injected mice were analyzed using the Nanostring nCounter immune panel. Peripheral mammary tumors significantly affected expression within the brain of over 100 unique genes of the 770 represented in the panel, and fewer than 25% of these genes were affected similarly across the day. Indeed, between 65 and 75% of GO biological processes represented by the differentially expressed genes were dependent upon time of day of sampling. The implications of time-of-day sampling bias in interpretation of research studies cannot be understated. We encourage considering time of day as a significant biological variable in studies and to appropriately control for it and clearly report time of day in findings.
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