Abstract 151P
Background
Metabolic rearrangement has been shown to be an important characteristic for stomach adenocarcinomas. Here we aimed to improve our understanding of the tumorigenesis of gastric cancer by means of gene and protein expression profile analysis with a focus on metabolic genes and pathways.
Methods
Array-based gene expression profiling of fresh frozen cancer tissues and adjacent normal tissues were obtained from 8 patients with gastric cancer at early stage by using Affymetrix oligonucleotide microarray. Assays targeted 179 unique genes related to cancer metabolism. The raw expression data were normalized using nSolver Analysis Software 3.0 and a dataset of gene expression ratios for GC vs. controls was generated. The p values were calculated using a paired t-test, and the threshold for up- and down-regulated genes was set at p value < 0.05. The protein expression of the dysregualted genes were detected by immunohistochemistry (IHC) in the formalin fixed paraffin embedded tissue blocks. The signal was quantified by the Allred score system which represented the estimated intensity and proportion of positive-staining cells.
Results
Our microarray results showed increased expression of 20 metabolic genes and decreased expression of 6 metabolic genes in all cases of gastric cancer at early stage. Besides of the undetected NOX4, the protein levels of all the others dysregualted genes, detected by IHC, showed consistently results. Half of all dysregulated genes (AKT2, EGLN3, G6PD, GLS, HIF1A, HK2, HRAS, MAP2K1, NTRK3, PGK1, PLCG1, RET and RPS6KB1) are implicated in Carbon Metabolism, a pivotal metabolic approach involving in nucleic acid biosynthesis. Five genes (ARNT, EGLN1, EGLN3, HIF1A and NOX4) are molecules implicated in hypoxia signaling. Besides, the upregulated HIF1A is a cancer metabolism driver, which means that HIF1A may induce the oncogenesis of gastric cancer.
Conclusions
The gastric mucosa in gastric cancer at early stage is characterized by dysregulated expression of a limited repertoire of metabolic genes. The nature of the corresponding metabolic rearrangement and pathways may help guide further investigations into its etiology.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
National Human Genetic Resources Sharing Service Platform (2005DKA21300), National Natural Science Foundation of China (81602078),.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
458P - Mutation tracking in circulating tumour DNA predicts relapse in completely resected EGFR-mutated NSCLC
Presenter: Martin Filipits
Session: Poster display session
Resources:
Abstract
460P - Mendelian randomization study showed no causality between metformin use and lung cancer risk
Presenter: Jiayi Shen
Session: Poster display session
Resources:
Abstract
461P - Blood trace minerals and lung cancer: A Mendelian randomization study
Presenter: Wei Xian
Session: Poster display session
Resources:
Abstract
463P - Prediction of invasiveness in lung adenocarcinoma using machine learning algorithm based on 3D-CT imaging
Presenter: Yusuke Saeki
Session: Poster display session
Resources:
Abstract
459P - Fish intake, dietary polyunsaturated fatty acids, and lung cancer: systematic review and dose-response meta-analysis of 1.7 million men and women
Presenter: Chao Cao
Session: Poster display session
Resources:
Abstract
462P - Usefulness for prevention of postoperative cerebrovascular complications in patients with lung cancer using carotid ultrasonography
Presenter: Sadanori Takeo
Session: Poster display session
Resources:
Abstract
468P - Histological type analysis of 10-year follow-up of WJTOG0105: A phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer
Presenter: Masahiro Tsuboi
Session: Poster display session
Resources:
Abstract
469P - Comparison of combined chemoradiotherapy regimens; Paclitaxel plus carboplatin and cisplatin plus etoposide for locally advanced non-small cell lung cancer: A randomised phase III trial
Presenter: Alper Ata
Session: Poster display session
Resources:
Abstract
472P - Integration of expression rate and absolute cell counts of PD-1+ stromal tumour-infiltrating lymphocytes: Prognostic significance in esophageal squamous cell carcinoma
Presenter: Qingkun Song
Session: Poster display session
Resources:
Abstract
467P - The free-circulating mtDNA copies number in plasma of patients with NSCLC
Presenter: Olga Bulgakova
Session: Poster display session
Resources:
Abstract