title: Elevated transcriptional levels of aldolase A (ALDOA) associates with cell cycle-related genes in patients with NSCLC and several solid tumors.
abstract: BACKGROUND
  Aldolase A (ALDOA) is one of the glycolytic enzymes primarily found in the developing embryo and adult muscle. Recently, a new role of ALDOA in several cancers has been proposed. However, the underlying mechanism remains obscure and inconsistent. In this study, we tried to investigate ALDOA-associated (AA) genes using available microarray datasets to help elucidating the role of ALDOA in cancer.
  
  
  RESULTS
  In the dataset of patients with non-small-cell lung cancer (NSCLC, E-GEOD-19188), 3448 differentially expressed genes (DEGs) including ALDOA were identified, in which 710 AA genes were found to be positively associated with ALDOA. Then according to correlation coefficients between each pair of AA genes, ALDOA-associated gene co-expression network (GCN) was constructed including 182 nodes and 1619 edges. 11 clusters out of GCN were detected by ClusterOne plugin in Cytoscape, and only 3 of them have more than three nodes. These three clusters were functionally enriched. A great number of genes (43/79, 54.4%) in the biggest cluster (Cluster 1) primarily involved in biological process like cell cycle process (Pa= 6.76E-26), mitotic cell cycle (Pa= 4.09E-19), DNA repair (Pa= 1.13E-04), M phase of meiotic cell cycle (Pa= 0.006), positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle (Pa= 0.014). AA genes with highest degree and betweenness were considered as hub genes of GCN, namely CDC20, MELK, PTTG1, CCNB2, CDC45, CCNB1, TK1 and PSMB2, which could distinguish cancer from normal controls with ALDOA. Their positive association with ALDOA remained after removing the effect of HK2 and PKM, the two rate limiting enzymes in glycolysis. Further, knocking down ALDOA blocked breast cancer cells in the G0/G1 phase under minimized glycolysis. All suggested that ALDOA might affect cell cycle progression independent of glycolysis. RT-qPCR detection confirmed the relationship of ALDOA with CDC45 and CCNB2 in breast tumors. High expression of the hub genes indicated poor outcome in NSCLC. ALDOA could improve their predictive power.
  
  
  CONCLUSIONS
  ALDOA could contribute to the progress of cancer, at least partially through its association with genes relevant to cell cycle independent of glycolysis. AA genes plus ALDOA represent a potential new signature for development and prognosis in several cancers.
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Jie-Diao
authors.initials: JD
authors.lastname: Lin
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060 China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zuo
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Zhuang
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Hong
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 USA.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Cui
authors.affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041 China.
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Cui
keywords: ALDOA; Cancer; Cell cycle; Transcripts