Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence
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ORIGINAL ARTICLE
Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence Sanae Kaji1,2 · Tomoyuki Irino1 · Masatoshi Kusuhara1,3 · Rie Makuuchi1 · Yushi Yamakawa1 · Masanori Tokunaga1 · Yutaka Tanizawa1 · Etsuro Bando1 · Taiichi Kawamura1 · Kenjiro Kami4 · Yoshiaki Ohashi4 · Shun Zhang2 · Hajime Orita2 · Hyeon‑Cheol Lee‑Okada5 · Tetsu Fukunaga2 · Masanori Terashima1 Received: 1 November 2019 / Accepted: 16 March 2020 © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2020
Abstract 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 2 mg/dL, aspartate transaminase > 100 IU/l, alanine transaminase > 100 IU/l); severe renal impairment (creatinine > 2 mg/dL); anti-hepatitis B surface antigen positivity, anti-hepatitis C antibody positivity, fluorescent treponemal antibody-absorption test positivity; blood coagulation disorder (hypochromia
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