2. Academic Validation
  3. SETD8 promotes stemness characteristics and is a potential prognostic biomarker of gastric adenocarcinoma

SETD8 promotes stemness characteristics and is a potential prognostic biomarker of gastric adenocarcinoma

  • Exp Mol Pathol. 2020 Dec;117:104560. doi: 10.1016/j.yexmp.2020.104560.
Lihua Piao 1,  Nan Che 2,  Haoyue Li 2,  Mengxuan Li 3,  Ying Feng 2,  Xingzhe Liu 2,  Seokhyung Kim 4,  Yu Jin 5,  Yanhua Xuan 6
Affiliations

Affiliations

  • 1 Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Histology and Embryology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China.
  • 2 Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China.
  • 3 Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Anatomy, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China.
  • 4 Department of Pathology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul 110-745, Republic of Korea.
  • 5 Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Anatomy, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China. Electronic address: [email protected].
  • 6 Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China. Electronic address: [email protected].
PMID: 33127342 DOI: 10.1016/j.yexmp.2020.104560
Abstract

SETD8 is a lysine methyltransferase containing an SET domain, which is involved in the carcinogenesis of many Cancer types through monomethylation of the histone H4 lysine 20. However, its prognostic value and underlying mechanisms in gastric adenocarcinoma (GA) have not been extensively studied. Here, we assessed SETD8 expression and its relationship with clinicopathological parameters, Cancer stemness-related proteins, cell cycle-related proteins, and PI3K/Akt pathway proteins in GA. SETD8 expression in GA tissues was correlated with the primary tumor stage, lymph node metastasis, tumor size, gross type, and clinical stage. SETD8 was an independent predictor of poor overall survival of patients with GA. COX regression analysis showed that SETD8 is a potential biomarker of unfavorable clinical outcomes in patients with GA. Moreover, SETD8 overexpression was associated with Cancer stemness-related genes, cell cycle-related genes, and PI3K/Akt/NF-κB pathway genes in clinical GA tissue samples. SETD8 silencing downregulated the expression of Cancer stemness-associated genes (LSD1 and SOX2) and inhibited GA cell proliferation, spheroid formation, invasion, and migration. Additionally, LY294002 significantly reduced the expression of SETD8, pAkt-Ser473, pPI3K-p85, and NFκB-p65 in MKN74 and MKN28 cells. SETD8 may be a novel Cancer stemness-associated protein and potential prognostic biomarker in GA.

Keywords

Cancer stemness; Gastric adenocarcinoma; Prognosis; SETD8.

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