细菌移位与癌性恶液质的关系及对恶液质患者结局的影响

Association of bacterial translocation with cachexia and its influence on the outcome of gastric cancer patients

目的探讨局限型进展期胃癌患者肠道细菌移位与恶液质的关系及其对患者结局的影响。方法选取2008年1月至2009年7月预行手术治疗的胃癌恶液质患者60例，年龄及性别匹配的胃癌非恶液质患者50例，健康对照者55例。采用聚合酶链反应检测外周血细菌DNA片段，酶联免疫吸附实验检测外周血细胞因子浓度，流式细胞法检测外周血免疫学指标。所有入选对象随访两年，计算两年生存率。结果恶液质组细菌移位发生率（15／60，25．0％）显著高于非恶液质组（4／50，8．0％，P=0．019）和健康对照组（0／55，0．0％，P=0．000）。细菌移位阳性的恶液质患者白细胞介素-1α（IL-1α）、IL-6、肿瘤坏死因子-α和干扰素-γ水平均显著高于细菌移位阴性的恶液质患者（P=0．012、P=0．003、P=0．036、P=0．017）和细菌移位阳性的非恶液质患者（P=0．011、P=0．034、P=0．000、P=0．022），并且其两年生存率明显低于细菌移位阴性的恶液质患者（P=0．023）。胃癌患者CD3^＋ T、CD4^＋ T和自然杀伤细胞水平及CD4^＋ T／CD8^＋ T显著低于健康对照组（P=0．023、P=0．031、P=0．016、P=0．041），CD8^＋ T细胞水平显著高于健康对照组（P=0．038）。结论肠道细菌移位可能与局限型进展期胃癌患者恶液质的发生有关，并影响恶液质患者的长期生存。

Objective To investigate the association of bacterial translocation （BT） with cachexia and its impact on the outcome of gastric cancer patients. Methods Sixty cachectic gastric cancer patients, 50 age- and sex-matched non-cachectic gastric cancer patients, and 55 healthy controls were enrolled in this study between January 2008 and July 2009. Polymerase chain reaction was performed to detect bacterial DNA in the peripheral blood of cancer patients and healthy controls. Cytokine levels were tested by enzyme-linked immunosorbent assay. Flow cytometry was used to detect immune indicators. All the enrolled patients were followed up for two years, and the two-year survival rate was calculated. Results The BT ratio was significantly higher in cachectic patients than in non-cachectic patients （25.0% vs. 8.0%, P = O. 019） and healthy controls （25.0% vs. 0. 0%, P = 0. 000）. BT-positive cachectic patients had significantly higher levels of IL-1α, IL-6, TNF-α, and IFN-γ compared with BT-negative cachectic patients （P = 0. 012, 0. 003, 0. 036, and 0. 017, respectively） and BT-positive non-cachectic patients （ P = 0. 011, 0. 034, 0. 000, and 0. 022, respectively）. The two-year survival rate in BT-positive cachectic patients was significantly lower than in BT-negative cachectic patients （ P = 0. 023 ）. The levels of CD3^＋ T, CD4^＋ T, natural killer cells, and CD4^＋ T/CD8^＋ T in gastric cancer patients were significantly lower than in healthy controls （P = 0. 023,0. 031,0. 016, 0. 041, respectively）, whereas CD8^＋ T level was significantly higher in gastric cancer patients than in healthy controls （P = 0. 038）. Conclusion BT may contribute to the development of cancer cachexia and influence the long-term survival of locally advanced gastric cancer patients.