目的 探讨晚期结肠癌患者的尿酸异常情况及其与临床病理特征和预后的关系。方法 回顾性分析98例IV期结肠癌患者的临床资料，分析结肠癌自然病程中尿酸异常的发生率，分析尿酸异常与患者的性别、年龄、发病部位、分化程度、肝转移、客观缓解率的关系。采用Kaplan-Meier法和多因素Cox回归模型分析尿酸异常对患者预后的影响。结果 98例患者中，尿酸增高者50例（51%），男性血清尿酸中位数为488.5（416.3，579.0）μmol/L，女性血清尿酸中位数为453.7（359.7，551.3）μmol/L。尿酸增高的发生与患者年龄、性别、发病部位无关，与癌细胞分化程度、肝转移有关（OR=6.315，P<0.01；OR=3.659，P<0.05）。尿酸正常组的客观缓解率是70.5%，明显高于尿酸增高组的28%（OR=6.245， P<0.01）。尿酸增高组的中位生存时间为22m（95%CI=19.923~24.077），尿酸正常组的中位生存时间为36m（95%CI=31.754~40.246）（HR=4.803，95%CI=2.970~7.769，P<0.01）。Cox多因素生存分析显示，血清尿酸为大肠癌患者预后的独立影响因素（P<0.05）。结论 晚期结肠癌患者自然病程中尿酸增高发生率高。尿酸增高的发生与细胞分化程度、肝转移、客观缓解率密切相关。血清尿酸为结肠癌患者预后的独立影响因素。
Objective To investigate the relationship of uric acid and clinicopathological features and prognosis of patients with advanced colon cancer. Methods The clinical data of 98 patients with stage IV colon cancer were collected and analyzed retrospectively. We analyzed the incidence of hyperuricemia during the natural course of colon cancer patients， and its relationship with the gender， age， degree of differentiation， liver metastasis of these patients. Kaplan-Meier method and multivariate Cox regression model were used to analyze the effect of hyperuricemia on prognosis. Results Among 98 cases of colon cancer patients， 50 (51%) cases were accompanied with hyperuricemia，those median was 488.5(416.3，579.0)μmol/L in male and 453.7(359.7，551.3)μmol/L in female。The incidence of hyperuricemia was marginally related to the gender， age and site (P>0.05) while significantly related to degree of differentiation and liver metastasis (OR=6.315，P<0.01;OR=3.659， P<0.05). The ORR of the patients without hyperuricemia was 70.5%， which is significantly higher than 28% in patients with hyperuricemia (OR=6.245， P<0.01). The median overall survival of the patients with hyperuricemia was 22 months (95%CI=20.915~27.085). It is significantly shorter than 36 months (95%CI=31.688~42.312) of patients without hyperuricemia (HR=4.803，95%CI=2.970~7.769，P<0.01). The results of Cox regression survival analysis showed that the incidence of hyperuricemia was independent factors of prognosis of patients with colon cancer (P<0.05). Conclusion During the natural course of advanced colon cancer， the incidence of hyperuricemia was high. The incidence of hyperuricemia are substantially correlated with degree of differentiation，liver metastasis and ORR. The incidence of hyperuricemia is independent prognosis factors of patients with colon cancer.
1.Ames BN， Cathcart R，Schwiers E， et al. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer: a hypothesis.Proc Natl Acad Sci U S A.1981;78(11):6858-6862.
2.Becker BF. Towards the physiological function of uric acid. Free Radic Biol Med. 1993;14(6):615-631.
3.Levine W， Dyer AR， Shekelle RB， et al. Serum uric acid and 11.5-year mortality of middle-aged women: findings of the chicago heart association detection project in industry. J Clin Epidemiol. 1989;42(3):257-267.
4.Strasak AM， Lang S， Kneib T， et al. Use of penalized splines in extended Cox-type additive hazard regression to flexibly estimate the effect of time-varying serum uric acid on risk of cancer incidence: a prospective， population-based study in 78，850 men. Ann Epidemiol. 2009;19(1):15-24.
5.Edge SB， Byrd DR， Compton CC， et al. AJCC cancer staging manual［M］.7th ed.New York:Springer，2010:143-146.
6.Eisenhauer EA， Therasse P， Bogaerts J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).Eur J Cancer. 2009;45(2):228-247.
7.Cetin AO， Omar M， Calp S， et al. Hyperuricemia at the time of diagnosis is a factor for poor prognosis in patients with stage II and III colorectal cancer. Asian Pac J Cancer Prev. 2017;18(2):485-490.
8.Yuan C， Xu XH，Wang XL， et al. Relationship between serum uric acid and metastatic and nonmetastatic rectal cancer patients with undergoing no chemotherapy. Medicine. 2016;95(47):e5463.
9.Dovell F， Boffetta P. Serum uric acid and cancer mortality and incidence: a systematic review and meta-analysis.Eur J Cancer Prev. 2015;27(4):399-405.
10.Dalamaga M， Diakopoulos KN， Mantzoros CS， et al. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012;33(4):547-594.
11.Mutoh M， Teraoka N， Takasu S， et al. Loss of adiponectin promotes intestinal carcinogenesis in min and wild-type mice. Gastroenterology. 2011;140(7):2000-2008;2008.e1-2.
12.Saxena NK， Fu PP， Nagalingam A， et al. Adiponectin modulates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma. Gastroenterology. 2010;139(5):1762-1773.
13.Baldwin W， McRae S， Marek G， et al. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes. 2011;60(4):1258-1269.
14.Lam JB， Chow KH， Xu A， et al. Adiponect in haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities. PLoS One. 2009;4(3):e4968.
15.Li G， Cong L， Gasser J， et al. Mechanisms underlying the anti-proliferative actions of adiponectin in human breast cancer cells， MCF7-dependency on the cAMP/protein kinase-A pathway. Nutr Cancer. 2011;63:80-88.
16.Baldwin W， McRae S， Marek G， et al. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes. 2011;60(4):1258-1269.
17.Battelli MG，Polito L， Bortolotti M， et al. Xanthine oxidoreductase in cancer: more than a differentiation marker. Cancer Med. 2016;5(3):546-557.
18.Chen YF， Li Q， Chen DT， et al. Prognostic value of pre-operative serum uric acid levels in esophageal squamous cell carcinoma patients who undergo R0 esophagectomy. Cancer Biomark. 2016;17(1):89-96.
19.Tanriverdi O， Cokmert S， Oktay E， et al. Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish descriptive oncological researches group. Med Oncol. 2014;31(10):217.
20.Stotz M， Szkandera J， Seidel J， et al. Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients. PLoS One. 2014;9(8):e104730.
