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
329P - High-level expression of HDAC10 is associated with PD-L1 expression and poor prognosis in patients with non-small cell lung cancer receiving pulmonectomy
Presenter: Xiaomei Liu
Session: Poster display session
Resources:
Abstract
331P - A retrospective analysis of immune checkpoint therapy in patients with non-small cell lung cancer: Focus on thyroid disorder
Presenter: Sawana Ono
Session: Poster display session
Resources:
Abstract
332P - Analyse the association between adverse events (AEs) and survival in patients treated with immune checkpoint inhibitors (ICIs)
Presenter: Chi-yuan Cheng
Session: Poster display session
Resources:
Abstract
333P - Study of searching on efficacy of immune checkpoint inhibitor for the non-small cell lung cancer using FDG-PET/CT and thallium SPECT
Presenter: KAYOKO Kibata
Session: Poster display session
Resources:
Abstract
334P - Incidence and characteristic of adrenal insufficiency due to immune checkpoint inhibitors therapy
Presenter: Daisuke Etoh
Session: Poster display session
Resources:
Abstract
335P - PD-L1 profile of nasopharyngeal cancer patients in Indonesia
Presenter: Handoko Handoko
Session: Poster display session
Resources:
Abstract
336P - Pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for PD-L1-positive advanced non-small cell lung cancer in the real world
Presenter: Jun Sugisaka
Session: Poster display session
Resources:
Abstract
337P - Neutrophil-to-Lymphocyte ratio as a predictive factor for hyperprogressive disease in NSCLC patients treated with immune checkpoint inhibitor
Presenter: Ryo Takahashi
Session: Poster display session
Resources:
Abstract
338P - A new insight into tumour immune-evasion: Crosstalk between cancer stem cells and T regulatory cells
Presenter: Abhishek Dutta
Session: Poster display session
Resources:
Abstract
339TiP - PACIFIC-5: Phase III study of durvalumab after either concurrent or sequential chemoradiotherapy (CRT) in patients with stage III NSCLC
Presenter: Yi-Long Wu
Session: Poster display session
Resources:
Abstract