A Transcriptomic Analysis of the Development of Skeletal Muscle Atrophy in Cancer-Cachexia in Tumor-Bearing Mice

We recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations prior to wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Overall design: Lewis Lung Carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. Muscle wasting was evident at 4 wks LLC. Animals were anesthetized using isoflourane and gastrocnemius muscles were collected for analysis. Conclusions: Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.

我们近期的研究证实，在癌症恶病质（Cancer Cachexia）的病程进展中，线粒体变性早于肌肉萎缩出现。然而，目前尚不清楚CC病程中肌肉萎缩发生前的肌内异常扰动程度。为此，我们针对CC诱导的肌肉萎缩开展了全基因组基因表达分析，以加深对CC整个发展过程中肌内异常改变的认知。

实验设计概述：于8周龄C57BL/6J小鼠的后胁部注射路易斯肺癌（Lewis Lung Carcinoma, LLC）细胞，待肿瘤分别生长1、2、3或4周后取材，并与磷酸盐缓冲液（PBS）注射的对照组小鼠进行对比。接种路易斯肺癌的小鼠在肿瘤生长第4周时即可出现明显的肌肉萎缩。采用异氟烷（isoflurane）对小鼠实施麻醉，随后收集腓肠肌用于后续分析。

研究结论：本研究结果为CC诱导的肌肉萎缩中的转录组表达变化与细胞通路异常提供了全新的实验证据。