Department of Electrical Engineering and Information Technology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran.
Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Sci Rep. 2021 Jan 27;11(1):2339. doi: 10.1038/s41598-021-81952-8.
The present study aimed to improve the understanding of non-uterine leiomyosarcoma (NULMS) prognostic genes through system biology approaches. This cancer is heterogeneous and rare. Moreover, gene interaction networks have not been reported in NULMS yet. The datasets were obtained from the public gene expression databases. Seven co-expression modules were identified from 5000 most connected genes; using weighted gene co-expression network analysis. Using Cox regression, the modules showed favorable (HR = 0.6, 95% CI = 0.4-0.89, P = 0.0125), (HR = 0.65, 95% CI = 0.44-0.98, P = 0.04) and poor (HR = 1.55, 95% CI = 1.06-2.27, P = 0.025) prognosis to the overall survival (OS) (time = 3740 days). The first one was significant in multivariate HR estimates (HR = 0.4, 95% CI = 0.28-0.69, P = 0.0004). Enriched genes through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) revealed significant immune-related pathways; suggesting immune cell infiltration as a favorable prognostic factor. The most significant protective genes were ICAM3, NCR3, KLRB1, and IL18RAP, which were in one of the significant modules. Moreover, genes related to angiogenesis, cell-cell adhesion, protein glycosylation, and protein transport such as PYCR1, SRM, and MDFI negatively affected the OS and were found in the other related module. In conclusion, our analysis suggests that NULMS might be a good candidate for immunotherapy. Moreover, the genes found in this study might be potential candidates for targeted therapy.
本研究旨在通过系统生物学方法提高对非子宫平滑肌肉瘤（NULMS）预后基因的理解。这种癌症具有异质性且罕见。此外，目前尚未报道 NULMS 的基因相互作用网络。数据集从公共基因表达数据库中获得。使用加权基因共表达网络分析，从 5000 个最相关基因中确定了 7 个共表达模块。使用 Cox 回归，模块显示出有利的（HR=0.6，95%CI=0.4-0.89，P=0.0125）、（HR=0.65，95%CI=0.44-0.98，P=0.04）和较差的（HR=1.55，95%CI=1.06-2.27，P=0.025）预后对总生存期（OS）（时间=3740 天）。第一个在多变量 HR 估计中具有统计学意义（HR=0.4，95%CI=0.28-0.69，P=0.0004）。通过数据库检索进行注释、可视化和综合发现（DAVID）富集的基因揭示了显著的免疫相关途径；表明免疫细胞浸润是一个有利的预后因素。最显著的保护基因是 ICAM3、NCR3、KLRB1 和 IL18RAP，它们位于一个重要的模块中。此外，与血管生成、细胞-细胞粘附、蛋白质糖基化和蛋白质转运相关的基因，如 PYCR1、SRM 和 MDFI，对 OS 有负面影响，并且存在于另一个相关模块中。总之，我们的分析表明，NULMS 可能是免疫治疗的一个很好的候选者。此外，本研究中发现的基因可能是靶向治疗的潜在候选者。
