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胃癌组织的代谢组学分析确定了预测腹膜复发的潜在生物标志物。

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

作者信息

Kaji Sanae, Irino Tomoyuki, Kusuhara Masatoshi, Makuuchi Rie, Yamakawa Yushi, Tokunaga Masanori, Tanizawa Yutaka, Bando Etsuro, Kawamura Taiichi, Kami Kenjiro, Ohashi Yoshiaki, Zhang Shun, Orita Hajime, Lee-Okada Hyeon-Cheol, Fukunaga Tetsu, Terashima Masanori

机构信息

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.

出版信息

Gastric Cancer. 2020 Sep;23(5):874-883. doi: 10.1007/s10120-020-01065-5. Epub 2020 Mar 26.

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 < 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.

摘要

背景

代谢组学有助于分析癌症进展所需的营养物质,因为细胞增殖受可用营养物质的调节。我们研究了胃癌(GC)组织的代谢组学特征,以阐明代谢与复发之间的关联。

方法

以配对方式从140例行胃切除术的GC患者中获取癌组织和相邻的非癌组织。将冷冻组织匀浆并通过毛细管电泳飞行时间质谱(CE-TOFMS)进行分析。根据是否复发进一步评估代谢物。

结果

定量了93种代谢物。在癌组织中,乳酸水平显著高于非癌组织,而腺苷酸能量电荷则较低。复发患者的天冬氨酸、β-丙氨酸、GDP和甘氨酸水平显著低于未复发患者。基于ROC分析确定这四种代谢物的临界值,将患者分为腹膜复发高风险和低风险组。逻辑回归和Cox比例风险分析确定β-丙氨酸是腹膜复发的独立预测因子(风险比[HR]5.21[95%置信区间1.07-35.89],p = 0.029)以及总生存的独立预后因素(HR 3.44[95%CI 1.65-7.14],p < 0.001)。

结论

癌组织的代谢组学特征与非癌组织不同。此外,四种代谢物与GC复发显著相关。β-丙氨酸既是腹膜复发的重要预测因子,也是一个预后因素。

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