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

Seong Woo Bae, Felix Berlth, Kyoung Yun Jeong, Ji Hyeon Park, Jong Ho Choi, Shin Hoo Park, Yun Suhk Suh, Seong Ho Kong, Do Joong Park, Hyuk Joon Lee, Charles Lee, Jong Il Kim, Hyewon Youn, Hongyoon Choi, Gi Jeong Cheon, Keon Wook Kang, Han Kwang Yang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)149-160
Number of pages12
JournalGastric Cancer
Volume25
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Gastric cancer
  • Gene signature
  • Patient-derived xenograft
  • Positron emission tomography

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