Research Institute of Medical Genetics, Tomsk National Research Medical Centre, Russian Academy of Sciences, 634050 Tomsk, Russia.
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 May 27;24(11):9385. doi: 10.3390/ijms24119385.
Cancer and neurodegenerative disorders present overwhelming challenges for healthcare worldwide. Epidemiological studies showed a decrease in cancer rates in patients with neurodegenerative disorders, including the Huntington disease (HD). Apoptosis is one of the most important processes for both cancer and neurodegeneration. We suggest that genes closely connected with apoptosis and associated with HD may affect carcinogenesis. We applied reconstruction and analysis of gene networks associated with HD and apoptosis and identified potentially important genes for inverse comorbidity of cancer and HD. The top 10 high-priority candidate genes included , , , , , , , , , and Functional analysis of these genes was carried out using gene ontology and KEGG pathways. By exploring genome-wide association study results, we identified genes associated with neurodegenerative and oncological disorders, as well as their endophenotypes and risk factors. We used publicly available datasets of HD and breast and prostate cancers to analyze the expression of the identified genes. Functional modules of these genes were characterized according to disease-specific tissues. This integrative approach revealed that these genes predominantly exert similar functions in different tissues. Apoptosis along with lipid metabolism dysregulation and cell homeostasis maintenance in the response to environmental stimulus and drugs are likely key processes in inverse comorbidity of cancer in patients with HD. Overall, the identified genes represent the promising targets for studying molecular relations of cancer and HD.
癌症和神经退行性疾病对全球的医疗保健构成了巨大挑战。流行病学研究表明，在包括亨廷顿病（HD）在内的神经退行性疾病患者中，癌症发病率下降。凋亡是癌症和神经退行性变的最重要过程之一。我们认为，与凋亡密切相关并与 HD 相关的基因可能会影响癌症的发生。我们应用与 HD 和凋亡相关的基因网络的重建和分析，确定了癌症和 HD 反合并症的潜在重要基因。排名前 10 的高优先级候选基因包括 、 、 、 、 、 、 、 、 和 。这些基因的功能分析是使用基因本体论和 KEGG 途径进行的。通过探索全基因组关联研究结果，我们确定了与神经退行性和肿瘤性疾病及其表型和危险因素相关的基因。我们使用公开的 HD 和乳腺癌、前列腺癌数据集来分析鉴定基因的表达。根据特定疾病的组织对这些基因的功能模块进行了表征。这种综合方法表明，这些基因在不同组织中主要发挥相似的功能。凋亡以及脂质代谢失调和细胞内稳态维持在对环境刺激和药物的反应中，可能是 HD 患者癌症反合并症的关键过程。总的来说，鉴定出的基因代表了研究癌症和 HD 分子关系的有前途的靶标。
