Integrative Analysis Reveals Across-Cancer Expression Patterns and Clinical Relevance of Ribonucleotide Reductase in Human Cancers
Integrative Analysis Reveals Across-Cancer Expression Patterns and Clinical Relevance of Ribonucleotide Reductase in Human Cancers
复制标题
综合分析揭示核糖核苷酸还原酶在人类癌症中的跨癌症表达模式和临床相关性
DOI：
10.3389/fonc.2019.00956
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发表时间：
2019-10-04
影响因子：
4.7
通讯作者：
Shao, Jimin
中科院分区：
文献类型：
--
作者：
Ding, Yongfeng;Zhong, Tingting;Shao, Jimin
挖掘癌症组学数据库加深了我们对癌症生物学的理解，并可能导致癌症治疗的潜在突破。在这里，我们提出了一种综合分析方法，以揭示跨癌症的表达模式，并确定潜在的临床影响，从五个代表性的公共数据库的基因。使用核糖核苷酸还原酶（RR），DNA合成和癌症治疗靶向的关键酶，作为一个例子，我们表征了三个RR亚基基因的mRNA表达谱和组分间的关联，并评估了它们在30多种癌症及其相关亚型中不同的病理和预后意义。通过免疫组化验证了从中国多个癌症中心收集的临床组织样本（n = 211）和临床随访的结果。使用共表达基因网络分析进一步探索和讨论了潜在的机制。这一框架代表了一种简单、高效、准确和全面的癌症组学资源分析方法，并强调了在分子生物标志物的临床评价过程中根据肿瘤的组织学或病理学亚型分离肿瘤的必要性。
Mining cancer-omics databases deepens our understanding of cancer biology and can lead to potential breakthroughs in cancer treatment. Here, we propose an integrative analytical approach to reveal across-cancer expression patterns and identify potential clinical impacts for genes of interest from five representative public databases. Using ribonucleotide reductase (RR), a key enzyme in DNA synthesis and cancer-therapeutic targeting, as an example, we characterized the mRNA expression profiles and inter-component associations of three RR subunit genes and assess their differing pathological and prognostic significance across over 30-types of cancers and their related subtypes. Findings were validated by immunohistochemistry with clinical tissue samples (n = 211) collected from multiple cancer centers in China and with clinical follow-up. Underlying mechanisms were further explored and discussed using co-expression gene network analyses. This framework represents a simple, efficient, accurate, and comprehensive approach for cancer-omics resource analysis and underlines the necessity to separate the tumors by their histological or pathological subtypes during the clinical evaluation of molecular biomarkers.