Glucose metabolic profiles evaluated by PET associated with molecular characteristic landscape of gastric cancer.

Document Type

Article

Publication Date

1-1-2022

Publication Title

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

Keywords

JGM, Fluorodeoxyglucose F18, Glucose, Glycine Plasma Membrane Transport Proteins, Humans, Metabolome, Positron-Emission Tomography, Radiopharmaceuticals, Stomach Neoplasms

JAX Source

Gastric Cancer 2022 Jan; 25(1):149-160

Volume

25

Issue

1

First Page

149

Last Page

160

ISSN

1436-3305

PMID

34363529

DOI

https://doi.org/10.1007/s10120-021-01223-3

Abstract

Background: Although FDG-PET is widely used in cancer, its role in gastric cancer (GC) is still controversial due to variable [18F]fluorodeoxyglucose ([18F]FDG) uptake. Here, we sought to develop a genetic signature to predict high FDG-avid GC to plan individualized PET and investigate the molecular landscape of GC and its association with glucose metabolic profiles noninvasively evaluated by [18F]FDG-PET.

Methods: Based on a genetic signature, PETscore, representing [18F]FDG avidity, was developed by imaging data acquired from thirty patient-derived xenografts (PDX). The PETscore was validated by [18F]FDG-PET data and gene expression data of human GC. The PETscore was associated with genomic and transcriptomic profiles of GC using The Cancer Genome Atlas.

Results: Five genes, PLS1, PYY, HBQ1, SLC6A5, and NAT16, were identified for the predictive model for [18F]FDG uptake of GC. The PETscore was validated in independent PET data of human GC with qRT-PCR and RNA-sequencing. By applying PETscore on TCGA, a significant association between glucose uptake and tumor mutational burden as well as genomic alterations were identified.

Conclusion: Our findings suggest that molecular characteristics are underlying the diverse metabolic profiles of GC. Diverse glucose metabolic profiles may apply to precise diagnostic and therapeutic approaches for GC.

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