Increased muscle ubiquitin mRNA levels in gastric cancer patients
Increased muscle ubiquitin mRNA levels in gastric cancer patients
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DOI：
10.1152/ajpregu.2001.280.5.r1518
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发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
Doglietto, GB
中科院分区：
文献类型：
--
作者：
Bossola, M;Muscaritoli, M;Doglietto, GB
肌内 ATP 依赖性泛素 (Ub) 蛋白酶体蛋白水解系统在实验性癌症恶病质中过度激活。本研究旨在验证癌症患者中肌肉 Ub mRNA 的表达是否发生改变。使用异硫氰酸胍/苯酚/氯仿方法从 20 名胃癌 (GC) 患者和 10 名接受手术的良性腹部疾病 (CON) 受试者术中获得的腹直肌活检中提取总肌肉 RNA。通过 Northern blot 分析测量 Ub mRNA 水平。通过ELISA测定血清可溶性肿瘤坏死因子受体(sTNFR)。 GC 中的 Ub mRNA 水平（任意单位，平均值 +/- SD）为 2,345 +/- 195，CON 中为 1,162 +/- 132（P = 0.0005）。 Ub mRNA 水平与疾病分期直接相关（r = 0.608，P = 0.005），I 期和 II 期为 1,945 +/- 786，III 期为 2,480 +/- 650，IV 期为 3,799 +/- 66。 Ub mRNA 和 sTNFR 与年龄和营养参数不相关。这项研究证实了实验数据表明癌症恶病质中肌肉 Ub mRNA 过度表达。与营养状况缺乏相关性表明，人类癌症中的泛素激活是出现恶病质任何临床症状之前的早期特征。
The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is hyperactivated in experimental cancer cachexia. The present study aimed at verifying whether the expression of the muscle Ub mRNA is altered in patients with cancer. Total muscle RNA was extracted using the guanidinium isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was measured by ELISA. Ub mRNA levels (arbitrary units, means +/- SD) were 2,345 +/- 195 in GC and 1,162 +/- 132 in CON (P = 0.0005). Ub mRNA levels directly correlated with disease stage (r = 0.608, P = 0.005), being 1,945 +/- 786 in stages I and II, 2,480 +/- 650 in stage III, and 3,799 +/- 66 in stage IV. Ub mRNA and sTNFR did not correlate with age and nutritional parameters. This study confirms experimental data indicating an overexpression of muscle Ub mRNA in cancer cachexia. Lack of correlation with nutritional status suggests that Ub activation in human cancer is an early feature that precedes any clinical sign of cachexia.