Ivanov Roman, Afonnikov Dmitry, Matushkin Yury, Lashin Sergey
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, Lavrentiev Avenue 10, 630090 Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, 2 Pirogova Str., 630090 Novosibirsk, Russia.
Int J Mol Sci. 2025 May 23;26(11):5041. doi: 10.3390/ijms26115041.
Cancer progression is a complex, multi-stage development process characterized by dynamic changes at the molecular level. Understanding these changes may provide new insights into tumorigenesis and potential therapeutic targets. This study focuses on the evolutionary transcriptomics of cancer, specifically analyzing the Transcriptome Age Index (TAI) across different pathological stages. By examining various cancers at four distinct pathological stages, we identify a significant «hourglass» pattern in TAI indices of ductal carcinoma of the breast, bladder carcinoma, and liver carcinoma, suggesting a conserved evolutionary trajectory during tumor development. The results reveal that early and late stages of these cancers exhibit higher TAI values, indicative of more novel gene expression, while intermediate stages show a dip in TAI, reflecting a more ancient evolutionary origin of expressed genes. This «hourglass» pattern underscores the evolutionary constraints and innovations at play during tumor progression. Our findings contribute to the growing body of evidence that evolutionary principles are deeply embedded in cancer biology, offering new perspectives on the dynamics of gene expression in tumors.
癌症进展是一个复杂的多阶段发展过程,其特征是分子水平上的动态变化。了解这些变化可能为肿瘤发生和潜在治疗靶点提供新的见解。本研究聚焦于癌症的进化转录组学,特别分析了不同病理阶段的转录组年龄指数(TAI)。通过检查处于四个不同病理阶段的各种癌症,我们在乳腺癌、膀胱癌和肝癌的TAI指数中发现了显著的“沙漏”模式,这表明肿瘤发展过程中存在保守的进化轨迹。结果显示,这些癌症的早期和晚期表现出较高的TAI值,表明有更多新的基因表达,而中间阶段的TAI则出现下降,反映出表达基因的进化起源更为古老。这种“沙漏”模式强调了肿瘤进展过程中起作用的进化限制和创新。我们的研究结果为越来越多的证据做出了贡献,即进化原理深深嵌入癌症生物学中,为肿瘤中基因表达的动态变化提供了新的视角。