Journal of Inflammation Research (Feb 2022)

Recovery of Dysregulated Genes in Cancer-Related Lower Limb Lymphedema After Supermicrosurgical Lymphaticovenous Anastomosis – A Prospective Longitudinal Cohort Study

  • Yang JCS,
  • Huang LH,
  • Wu SC,
  • Wu YC,
  • Wu CJ,
  • Lin CW,
  • Tsai PY,
  • Chien PC,
  • Hsieh CH

Journal volume & issue
Vol. Volume 15
pp. 761 – 773

Abstract

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Johnson Chia-Shen Yang,1,2 Lien-Hung Huang,1,2 Shao-Chun Wu,3,4 Yi-Chan Wu,1,4 Chia-Jung Wu,1,4 Chia-Wei Lin,1,4 Pei-Yu Tsai,1,4 Peng-Chen Chien,1,4 Ching-Hua Hsieh1,2 1Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4Chang Gung University College of Medicine, Taoyuan, TaiwanCorrespondence: Ching-Hua HsiehGraduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, 123 Dapi Road, Niaosong District, Kaohsiung City, 833, Taiwan, Tel +886-7-7317123, ext.8002, Fax +886-7-7354309, Email [email protected]: This study aims at profiling the expression of dysregulated genes in circulating monocytes of patients with cancer-related lower limb lymphedema before and after treatment with supermicrosurgical lymphaticovenous anastomosis (LVA).Materials and Methods: This prospective longitudinal cohort study enrolled 51 women with post-treatment gynecological cancer, including those with unilateral lymphedema (study group, n = 25) and those without (control group, n = 26). Venous blood samples obtained from the study group before and after LVA and those from the controls were sent for next-generation sequencing, which was validated by real-time PCR. Dysregulated gene expression in the study group, relative to expression in the controls, was recorded before LVA. After one month, postoperative changes in the expression of the identified genes were evaluated. Protein-protein interaction (PPI) was used to investigate dysregulated genes whose expression returned to baseline levels after LVA.Results: Of the 148 preoperative dysregulated genes, which comprised 108 up- and 40 down-regulated genes, 78 genes, consisting of 69 up- and 9 down-regulated genes, showed post-LVA recovery to baseline levels. Through PPI analysis, five functional modules involving immunity, lipid metabolism, oxidative stress, transcriptional regulators, and tumor suppression, as well as six hub genes (CCL2, LPL, PDK4, FOXO3, EGR1, and DUSP5), were identified. Cross-linking and co-regulated genes between modules were also identified.Conclusion: Localized lymphedema leads to dysregulated gene expression in circulating monocytes. The current study is the first to identify the hub genes related to lymphedema and demonstrate the recovery of some dysregulated genes after LVA.Keywords: transcriptome, NGS, real-time PCR, hub gene, functional modules

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