title: Elucidation of drivers of high-level production of lactates throughout a cancer development.
abstract: 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.
authors.affiliation: Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA, USA Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Cao
authors.affiliation: Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA, USA College of Computer Science and Technology, Jilin University, Changchun, China School of Public Health, Jilin University, Changchun, China xyn@bmb.uga.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism*; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D045022:Lactate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D009369:Neoplasms / Q000201:enzymology*; D011230:Precancerous Conditions / Q000201:enzymology; D013312:Stress, Physiological
chemical_list: D007773:Lactates; D045022:Lactate Dehydrogenases
keywords: cancer progression; gene co-expression analysis; lactic acids