Department of Oncological Radiotherapy, Affiliated Hospital of Medical College Qingdao University, Shandong, China.
Mol Genet Genomics. 2021 Mar;296(2):369-378. doi: 10.1007/s00438-020-01747-w. Epub 2021 Jan 15.
The tradeoff between cost and efficiency is omnipresent in organisms. Specifically, how the evolutionary force shapes the tradeoff between biosynthetic cost and translation efficiency remains unclear. In the cancer community, whether the adjustment of cost-efficiency tradeoff acts as a strategy to facilitate tumor proliferation and contributes to oncogenesis is uninvestigated. To address this issue, we retrieved the gene expression profile in various cancer types and the matched normal samples from The Cancer Genome Atlas (TCGA). We found that the highly expressed genes in cancers generally have higher tAI/nitro ratios than those in normal samples. This is possibly caused by the higher tAI/nitro ratios observed in oncogenes than tumor suppressor genes (TSG). Furthermore, in the cancer samples, derived mutations in oncogenes usually lead to higher tAI/nitro ratios, while those mutations in TSG lead to lower tAI/nitro. For a special case of kidney cancer, we investigated several crucial genes in tumor samples versus normal samples, and discovered that the changes in tAI/nitro ratios are correlated with the changes in translation level. Our study for the first time revealed the optimization of cost-efficiency tradeoff in cancers. The cost-efficiency dilemma is optimized by the tumor cells, and is possibly beneficial for the translation and production of oncogenes, and eventually contributes to proliferation and oncogenesis. Our findings could provide novel perspectives in depicting the cancer genomes and might help unravel the cancer evolution.
成本与效率之间的权衡在生物体中无处不在。具体来说,进化力量如何塑造生物合成成本与翻译效率之间的权衡仍不清楚。在癌症领域,成本效率权衡的调整是否作为促进肿瘤增殖的策略,以及是否有助于肿瘤发生,尚未得到研究。为了解决这个问题,我们从癌症基因组图谱(TCGA)中检索了各种癌症类型和匹配的正常样本的基因表达谱。我们发现,癌症中高表达的基因通常比正常样本具有更高的 tAI/nitro 比值。这可能是由于致癌基因中的 tAI/nitro 比值高于肿瘤抑制基因(TSG)。此外,在癌症样本中,致癌基因的衍生突变通常导致更高的 tAI/nitro 比值,而 TSG 中的突变则导致更低的 tAI/nitro。对于肾癌的一个特殊情况,我们研究了肿瘤样本与正常样本中的几个关键基因,发现 tAI/nitro 比值的变化与翻译水平的变化相关。我们的研究首次揭示了癌症中成本效率权衡的优化。肿瘤细胞优化了成本效率困境,这可能有利于致癌基因的翻译和产生,最终有助于增殖和肿瘤发生。我们的发现可以为描绘癌症基因组提供新的视角,并有助于揭示癌症进化。