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Correlations between metabolic texture features, genetic heterogeneity, and mutation burden in patients with lung cancer

  • Seung Hwan MoonEmail author
  • Jinho Kim
  • Je-Gun Joung
  • Hongui Cha
  • Woong-Yang Park
  • Jin Seok Ahn
  • Myung-Ju Ahn
  • Keunchil Park
  • Joon Young Choi
  • Kyung-Han Lee
  • Byung-Tae Kim
  • Se-Hoon LeeEmail author
Original Article
  • 328 Downloads

Abstract

Purpose

This study investigated the correlations between parameters of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan and indices of genetic properties, heterogeneity index (HI), and tumor mutation burden (TMB), in patients with lung cancer.

Methods

We produced 106 PET indices for each tumor site that underwent genomic analysis in a total of 176 study subjects (age, 62.0 ± 10.0 y; males, 68.2%), comprising 101 adenocarcinoma (ADC), 29 squamous cell carcinoma (SQCC), and 46 small cell lung cancer (SCLC) patients. We then examined the correlations of the PET parameters with genetic properties of HI and TMB, according to pathology and tumor site.

Results

Comparisons between PET parameters and the genetic properties with false discovery rate (FDR) correction revealed that the surface standard uptake value (SUV) entropy of SUV statistics had a significant correlation with HI only in patients with SCLC who underwent a genetic test in lymph nodes (r = 0.592, p = 0.028), whereas PET parameters did not show a significant correlation with HI or TMB in patients with SCLC who underwent a genetic test in lung tissue. In patients with ADC and SQCC, there was no significant correlation between PET parameters and the genetic properties. Although SUVmax showed raw p values less than 0.05 in correlation with HI (r = 0.315, raw p = 0.048) and TMB (r = 0.206, raw p = 0.043) in ADC, and SUVpeak had a raw p value less than 0.05 in correlation with HI (r = 0.394, raw p = 0.046) in SQCC, these parameters were not significant when corrected by FDR.

Conclusions

In this study, surface SUV entropy had a significant correlation with HI in SCLC. Regarding other PET parameters and tumors, no significant correlation with genetic parameters existed.

Keywords

18F-fluorodeoxyglucose (FDG) Positron emission tomography (PET) Imaging genomics Genetic heterogeneity Tumor mutation burden 

Notes

Acknowledgements

The authors thank Kyunga Kim and Min-Ji Kim from the Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center for their important contributions to our statistical analysis. They also thank Yu-Hua Fang from Department of Biomedical Engineering, National Cheng Kung University and Hongyoon Choi from Department of Nuclear Medicine, Seoul National University Hospital for their important contributions to our imaging analysis.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No.NRF-2016R1C1B2013411).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The institutional review board approved that the requirement for written informed consents were waived in this study.

Supplementary material

259_2018_4138_Fig2_ESM.png (989 kb)
Supplemental Figure 1

The variance of FDG PET features. CV of non-texture features (a) and texture features (b) which were obtained from nine different volumetric tumor segmentations on PET/CT are plotted. CV, Coefficient of variance (PNG 989 kb)

259_2018_4138_MOESM1_ESM.tif (74 kb)
High resolution image a (TIF 74 kb)
259_2018_4138_Fig3_ESM.png (2.2 mb)

b (PNG 2228 kb)

259_2018_4138_MOESM2_ESM.tif (126 kb)
High resolution image b (TIF 126 kb)
259_2018_4138_MOESM3_ESM.jpeg (179 kb)
Supplemental Figure 2 Visualization of the correlation between genetic parameters and image features of PET/CT. Heatmaps of correlation values of 30 PET features with HI in 113 subjects (a) and TMB in 176 subjects (b) according to tumor pathology and site are illustrated. HI, heterogenetic index; TMB, tumor mutation burden (JPEG 178 kb)
259_2018_4138_MOESM4_ESM.jpeg (188 kb)
b (JPEG 187 kb)
259_2018_4138_MOESM5_ESM.docx (33 kb)
Supplemental Table 1 (DOCX 32 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Seung Hwan Moon
    • 1
    Email author
  • Jinho Kim
    • 2
  • Je-Gun Joung
    • 2
  • Hongui Cha
    • 2
    • 3
  • Woong-Yang Park
    • 4
  • Jin Seok Ahn
    • 5
  • Myung-Ju Ahn
    • 5
  • Keunchil Park
    • 5
  • Joon Young Choi
    • 1
  • Kyung-Han Lee
    • 1
  • Byung-Tae Kim
    • 1
  • Se-Hoon Lee
    • 3
    • 5
    Email author
  1. 1.Department of Nuclear Medicine and Molecular ImagingSamsung Medical CenterSeoulRepublic of Korea
  2. 2.Samsung Genome InstituteSamsung Medical CenterSeoulRepublic of Korea
  3. 3.Department of Health Sciences and Technology, SAIHSTSungkyunkwan UniversitySeoulRepublic of Korea
  4. 4.Samsung Genome Institute, Samsung Medical Center, Samsung Advanced Institute of Health Science and Technology, Department of Molecular Cell BiologySungkyunkwan University School of MedicineSeoulRepublic of Korea
  5. 5.Division of Hematology/Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea

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