Belotti Yuri, Tolomeo Serenella, Yu Rongjun, Lim Wan-Teck, Lim Chwee Teck
Institute for Health Innovation and Technology, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore.
Institute of High Performance Computing, Agency for Science, Technology and Research (A*STAR), 1 Fusionopolis Way, Singapore 138632, Singapore.
Cancers (Basel). 2022 May 21;14(10):2544. doi: 10.3390/cancers14102544.
Glioblastoma multiforme (GBM) is one of the most aggressive forms of cancer. Neurotransmitters (NTs) have recently been linked with the uncontrolled proliferation of cancer cells, but the role of NTs in the progression of human gliomas is still largely unexplored. Here, we investigate the genes encoding for neurotransmitter receptors (NTRs) by analyzing public transcriptomic data from GBM and LGG (low-grade glioma) samples. Our results showed that 50 out of the 98 tested NTR genes were dysregulated in brain cancer tissue. Next, we identified and validated NTR-associated prognostic gene signatures for both LGG and GBM. A subset of 10 NTR genes (, , , , , , , , , and ) predicted a positive prognosis in LGG and a negative prognosis in GBM. These genes were progressively downregulated across glioma grades and exhibited a strong negative correlation with genes associated with immune response, inflammasomes, and established cancer hallmarks genes in lower grade gliomas, suggesting a putative role in inhibiting cancer progression. This study might have implications for the development of novel therapeutics and preventive strategies that target regulatory networks associated with the link between the autonomic nervous system, cancer cells, and the tumor microenvironment.
多形性胶质母细胞瘤（GBM）是最具侵袭性的癌症形式之一。神经递质（NTs）最近被认为与癌细胞的不受控制增殖有关，但NTs在人类胶质瘤进展中的作用仍 largely unexplored（大部分未被探索）。在这里，我们通过分析来自GBM和低级别胶质瘤（LGG）样本的公开转录组数据来研究编码神经递质受体（NTRs）的基因。我们的结果表明，在98个测试的NTR基因中，有50个在脑癌组织中表达失调。接下来，我们为LGG和GBM鉴定并验证了与NTR相关的预后基因特征。10个NTR基因的一个子集（此处未列出具体基因名称）在LGG中预测预后良好，而在GBM中预测预后不良。这些基因在胶质瘤分级中逐渐下调，并且在低级别胶质瘤中与免疫反应、炎性小体以及已确定的癌症标志基因相关的基因呈现出强烈的负相关，表明其在抑制癌症进展中可能发挥作用。这项研究可能对开发针对与自主神经系统、癌细胞和肿瘤微环境之间联系相关的调控网络的新型治疗方法和预防策略具有启示意义。
