방사선의학 웹진

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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.

Affiliations

Seong-Woo Bae #  1 , Felix Berlth #  2 , Kyoung-Yun Jeong  1 , Ji-Hyeon Park  3 , Jong-Ho Choi  3 , Shin-Hoo Park  3 , Yun-Suhk Suh  3 , Seong-Ho Kong  3 , Do-Joong Park  3 , Hyuk-Joon Lee  1   3 , Charles Lee  4 , Jong-Il Kim  1   5 , Hyewon Youn  1   6 , Hongyoon Choi  7 , Gi Jeong Cheon  1   6 , Keon Wook Kang  1   6 , Han-Kwang Yang  8   9
1 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
2 Department of General, Visceral and Transplant Surgery, University of Mainz, Mainz, Germany.
3 Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
4 The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
5 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
6 Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
7 Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. hkyang@snu.ac.kr.
8 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. hkyang@snu.ac.kr.
9 Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. hkyang@snu.ac.kr.
# Contributed equally.