Elucidation of drivers of high-level production of lactates throughout a cancer development  

作　　者：Chi Zhang Chao Liu Sha Cao Ying Xu 

机构地区：[1]Computational Systems Biology Lab,Department of Biochemistry and Molecular Biology and Institute of Bioinformatics,University of Georgia,Athens,GA,USA [2]Department of Oral and Maxillofacial Surgery,Shandong Provincial Hospital Affiliated to Shandong University,Jinan,China [3]College of Computer Science and Technology,Jilin University,Changchun,China [4]School of Public Health,Jilin University,Changchun,China

出　　处：《Journal of Molecular Cell Biology》2015年第3期267-279,共13页分子细胞生物学报（英文版）

基　　金：This work is supported by Georgia Research Alliance,USA and the Technology Development Plan Project of Shandong Province,China(Grant No.2014GSF1181).

摘　　要：Lactates play key roles in facilitating or protecting the development of a cancer in most cancer types.While its beneficial effects to cancer development have been extensively studied,very little is known about what derives the high-level production of lactates in a cancer throughout its entire development.Here we present a novel computational analysis of transcriptomic data of nine primary cancer types,plus a few precancerous and metastatic cancer,to address this issue.Our approach is to identify stress types,which are known to play key roles in cancer development and show strong co-expressions with lactate dehydrogenase-A(LDHA),at different stages of cancer development.A number of interesting observations are made through our analyses,including(i)all nine primary cancer types show similar association patterns between stresses and LDHA,namely the strengths of the associations increase from early-to intermediate-stage cancer tissues but then make a substantial down turn at the most advanced stage;(ii)while the detailed stress types associated with LDHA may vary across different cancer types,stresses induced by apoptosis and adaptive immune responses are present universally,suggesting that these two stresses are possibly two key drivers to keep the high-level production of lactates;and(iii)there is a clear distinction between stress types associated with LDHA in precancerous tissues vs.cancer and metastasis tissues.We anticipate that the analyses can provide highly useful information for designing personalized treatments for different cancers at different stages,as stopping lactate production could have devastating effects on a cancer development.

关 键 词：cancer progression lactic acids gene co-expression analysis 

分 类 号：R73[医药卫生—肿瘤]