Overexpression of hydroxyproline via EGLN/HIF1A is associated with distant metastasis in pancreatic cancer.

EGLN HIF1A distant metastasis hydroxyproline pancreatic cancer

Journal

American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944

Informations de publication

Date de publication:
2020
Historique:
received: 07 11 2019
accepted: 10 01 2020
entrez: 9 9 2020
pubmed: 10 9 2020
medline: 10 9 2020
Statut: epublish

Résumé

For pancreatic cancer, the probability of distant metastasis can help choose the best course of treatment. The aim of this study is to establish the efficacy of hydroxyproline as a biomarker for distant metastasis for pancreatic cancer and to clarify the mechanism of EGLN/HIF1A axis that controls the invasion and metastasis. Metabolites (hydroxyproline) and genes (EGLN2 and EGLN3) were identified by metabolome analysis of the serum with pancreatic cancers with and without distant metastasis. The mechanism of EGLN/HIF1A axis including angiogenesis was examined in pancreatic cancer cells. Hydroxyproline associated with these mechanisms was evaluated to suggest the association with overall survival in pancreatic cancer. Decreased expression of EGLN2 and EGLN3 in pancreatic cancer, via the HIF1A and TGF ß1 pathway, was associated with the induction of angiogenic factors, increased vascular invasion, and poor overall patient survival. Hydroxyproline concentrations were regulated via the HIF1A pathway by EGLN2 and EGLN3, and that increased concentrations of hydroxyproline promote the invasion and metastasis of pancreatic cancer cells. These results suggested that the expression of hydroxyproline through the HIF1A pathway induced by EGLN2 and EGLN3 could be a surrogate marker for treatment and might predict distant metastasis in pancreatic cancer.

Identifiants

pubmed: 32905516
pmc: PMC7471362

Types de publication

Journal Article

Langues

eng

Pagination

2570-2581

Informations de copyright

AJCR Copyright © 2020.

Déclaration de conflit d'intérêts

None.

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Auteurs

Naokazu Chiba (N)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Makoto Sunamura (M)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Masashi Nakagawa (M)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Itsuki Koganezawa (I)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Kei Yokozuka (K)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Toshimichi Kobayashi (T)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Kosuke Hikita (K)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Yosuke Ozawa (Y)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Masaaki Okihara (M)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Toru Sano (T)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Koichi Tomita (K)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Rina Tsutsui (R)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Masahiro Sugimoto (M)

Research and Development Center for Minimally Invasive Therapies Health Promotion and Preemptive Medicine, Tokyo Medical University Tokyo, Japan.

Shigeyuki Kawachi (S)

Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center Tokyo, Japan.

Classifications MeSH