Ann Surg Treat Res.  2019 Apr;96(4):153-161. 10.4174/astr.2019.96.4.153.

Genetic features associated with ¹⁸F-FDG uptake in intrahepatic cholangiocarcinoma

• Ahn KS
• Kang KJ
• Kim YH
• Kim TS
• Song BI
• Kim HW
• O'Brien D
• Roberts LR
• Lee JW
• Won KS

• KMID: 2442209
• DOI: http://doi.org/10.4174/astr.2019.96.4.153

Abstract

PURPOSE
In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on ¹â¸F-fluorodeoxyglucose (¹â¸F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns.
METHODS
We performed RNA sequencing of 22 cases iCCA who underwent preoperative ¹â¸F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed.
RESULTS
Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients.
CONCLUSION
The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.

Keyword

Cholangiocarcinoma; Fluorodeoxyglucose F18; Positron-emission tomography; Gene expression; Cell cycle

MeSH Terms

Anoxia
Cell Cycle
Cell Division
Cholangiocarcinoma*
Disease-Free Survival
Fluorodeoxyglucose F18
Gene Expression
Gluconeogenesis
Glycolysis
Humans
Metabolism
Phosphorylation
Positron-Emission Tomography
Sequence Analysis, RNA
Transcriptome
Fluorodeoxyglucose F18

Figure

• 

  Fig. 1 Disease-free survival (A) and overall survival (B) according to high and low maximum standard uptake value (SUVmax).

• 

  Fig. 2 Genes significantly correlated with maximum standard uptake value (SUVmax). LRRC59 (A), KIFC1 (B), LSM12 (C), BYSL (D), and RRM2 (E) were positively correlated, while SLC27A2 (F) was negatively correlated with SUVmax.

• 

  Fig. 3 According to the gene set enrichment analysis (GSEA), patients with high maximum standard uptake value (higher than 9.0) were characterized by activated cell cycle (A), E2F target (B), G2M checkpoint (C), MYC target (D), Glycolysis (E), and tumor necrosis factor alpha signaling pathway (F).

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