Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.


Journal

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238

Informations de publication

Date de publication:
09 2020
Historique:
received: 01 11 2019
accepted: 16 03 2020
pubmed: 29 3 2020
medline: 29 6 2021
entrez: 29 3 2020
Statut: ppublish

Résumé

Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Sections du résumé

BACKGROUND
Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence.
METHODS
Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence.
RESULTS
Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001).
CONCLUSIONS
The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Identifiants

pubmed: 32219586
doi: 10.1007/s10120-020-01065-5
pii: 10.1007/s10120-020-01065-5
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

874-883

Auteurs

Sanae Kaji (S)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Bunkyo‑ku, Tokyo, 113-8431, Japan.

Tomoyuki Irino (T)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Masatoshi Kusuhara (M)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
Shizuoka Cancer Center Research Institute, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Rie Makuuchi (R)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Yushi Yamakawa (Y)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Masanori Tokunaga (M)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Yutaka Tanizawa (Y)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Etsuro Bando (E)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Taiichi Kawamura (T)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Kenjiro Kami (K)

Human Metabolome Technologies, Inc, Tsuruoka, Yamagata, 997-0052, Japan.

Yoshiaki Ohashi (Y)

Human Metabolome Technologies, Inc, Tsuruoka, Yamagata, 997-0052, Japan.

Shun Zhang (S)

Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Bunkyo‑ku, Tokyo, 113-8431, Japan.

Hajime Orita (H)

Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Bunkyo‑ku, Tokyo, 113-8431, Japan.

Hyeon-Cheol Lee-Okada (HC)

Department of Biochemistry, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, 113-8431, Japan.

Tetsu Fukunaga (T)

Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Bunkyo‑ku, Tokyo, 113-8431, Japan.

Masanori Terashima (M)

Division of Gastric Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. m.terashima@scchr.jp.

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