Chen Jia-Hong, Wu Alexander T H, Lawal Bashir, Tzeng David T W, Lee Jih-Chin, Ho Ching-Liang, Chao Tsu-Yi
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defence Medical Center, Taipei City 114, Taiwan.
Cancers (Basel). 2021 Jul 30;13(15):3847. doi: 10.3390/cancers13153847.
Despite the significant advancement in therapeutic strategies, breast, colorectal, gastric, lung, liver, and prostate cancers remain the most prevalent cancers in terms of incidence and mortality worldwide. The major causes ascribed to these burdens are lack of early diagnosis, high metastatic tendency, and drug resistance. Therefore, exploring reliable early diagnostic and prognostic biomarkers universal to most cancer types is a clinical emergency. Consequently, in the present study, the differentially expressed genes (DEGs) from the publicly available microarray datasets of six cancer types (liver, lung colorectal, gastric, prostate, and breast cancers), termed hub cancers, were analyzed to identify the universal DEGs, termed hub genes. Gene set enrichment analysis (GSEA) and KEGG mapping of the hub genes suggested their crucial involvement in the tumorigenic properties, including distant metastases, treatment failure, and survival prognosis. Notably, our results suggested high frequencies of genetic and epigenetic alterations of the DEGs in association with tumor staging, immune evasion, poor prognosis, and therapy resistance. Translationally, we intended to identify a drug candidate with the potential for targeting the hub genes. Using a molecular docking platform, we estimated that ovatodiolide, a bioactive anti-cancer phytochemical, has high binding affinities to the binding pockets of the hub genes. Collectively, our results suggested that the hub genes were associated with establishing an immune-suppressive tumor microenvironment favorable for disease progression and promising biomarkers for the early diagnosis and prognosis in multiple cancer types and could serve as potential druggable targets for ovatodiolide.
尽管治疗策略取得了显著进展，但乳腺癌、结直肠癌、胃癌、肺癌、肝癌和前列腺癌在全球发病率和死亡率方面仍然是最常见的癌症。造成这些负担的主要原因是缺乏早期诊断、高转移倾向和耐药性。因此，探索适用于大多数癌症类型的可靠早期诊断和预后生物标志物是一项临床急症。因此，在本研究中，对来自六种癌症类型（肝癌、肺癌、结直肠癌、胃癌、前列腺癌和乳腺癌）公共微阵列数据集的差异表达基因（DEG）进行分析，以识别通用的DEG，即枢纽基因。枢纽基因的基因集富集分析（GSEA）和KEGG映射表明它们在肿瘤发生特性中起关键作用，包括远处转移、治疗失败和生存预后。值得注意的是，我们的结果表明，DEG的遗传和表观遗传改变频率较高，与肿瘤分期、免疫逃逸、预后不良和治疗耐药性相关。在转化方面，我们旨在鉴定一种有可能靶向枢纽基因的候选药物。使用分子对接平台，我们估计，一种具有生物活性的抗癌植物化学物质卵叶二内酯对枢纽基因的结合口袋具有高结合亲和力。总体而言，我们的结果表明，枢纽基因与建立有利于疾病进展的免疫抑制肿瘤微环境相关，是多种癌症类型早期诊断和预后的有前景的生物标志物，并且可以作为卵叶二内酯潜在的可药物靶点。
