The serum uric acid (SUA) is the end-product from the metabolic breakdown of purine nucleotides. It has been considered to be a prognostic factor for malignant tumor in several researches. However, its prognostic value in patients with esophageal squamous cell carcinoma (ESCC) has not been elucidated.
METHODS:
We retrospectively reviewed the records of 209 ESCC patients who underwent R0 esophagectomy. A receiver operating characteristic(ROC) curve analysis was used to determine the optimal cut-off value for pre-operative SUA levels and to divide the ESCC patients into two groups. Furthermore, we analyzed the pre-operative serum uric acid (SUA) levels and its relationship with the clinicopathological parameters and the prognosis of 209 ESCC patients.
RESULTS:
Optimal cut-off value for pre-operative SUA in ROC analysis was 304.5 μ mol/l (sensitivity 67.46%, specificity 65.06%). SUA low- or high-levels were associated with gender(P< 0.001), smoking status (P< 0.001), pN statues (P= 0.003) and TNM stage(P= 0.010). SUA levels, tumor differentiation and pTNM stage were independent predictors of ESCC patient survival in a multivariate analysis.
CONCLUSIONS:
The pre-operative level of SUA is an independent prognostic predictor in ESCC patients who undergo R0 esophagectomy and patients with higher SUA level may have an unfavorable survival probability.
FerlayJ., SoerjomataramI., DikshitR., EserS., MathersC., RebeloM., ParkinD.M., FormanD. and BrayF., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012, Int J Cancer136 (2015), E359-86.
2.
ArnoldM., SoerjomataramI., FerlayJ. and FormanD., Global incidence of oesophageal cancer by histological subtype in 2012, Gut64 (2015), 381-7.
3.
LinY., TotsukaY., HeY., KikuchiS., QiaoY., UedaJ., WeiW., InoueM. and TanakaH., Epidemiology of esophageal cancer in Japan and China, J Epidemiol23 (2013), 233-42.
4.
GuoP. and LiK., Trends in esophageal cancer mortality in China during 1987-2009: age, period and birth cohort analyzes, Cancer Epidemiol36 (2012), 99-105.
5.
EnzingerP.C. and MayerR.J., Esophageal cancer, N Engl J Med349 (2003), 2241-52.
6.
LiX.H., WangX.P., GuW.S., LinJ.H., HuangH., KangT., ZhangL., ChenH. and ZhengX., Clinical Significance of Preoperative Thrombin Time in Patients with Esophageal Squamous Cell Carcinoma following Surgical Resection, PLoS One10 (2015), e0140323.
7.
QinJ., WuS.G., SunJ.Y., LinH.X., HeZ.Y. and LiQ., Effect of blood type on survival of Chinese patients with esophageal squamous cell carcinoma, Onco Targets Ther8 (2015), 947-53.
8.
FiniM.A., EliasA., JohnsonR.J. and WrightR.M., Contribution of uric acid to cancer risk, recurrence, and mortality, Clin Transl Med1 (2012), 16.
9.
YanS., ZhangP., XuW., LiuY., WangB., JiangT., HuaC., WangX., XuD. and SunB., Serum Uric Acid Increases Risk of Cancer Incidence and Mortality: A Systematic Review and Meta-Analysis, Mediators Inflamm2015 (2015), 764250.
10.
DziamanT., BanaszkiewiczZ., RoszkowskiK., GackowskiD., WisniewskaE., RozalskiR., FoksinskiM., SiomekA., SpeinaE., WinczuraA., MarszalekA., TudekB. and OlinskiR., 8-Oxo-7, 8-dihydroguanine and uric acid as efficient predictors of survival in colon cancer patients, Int J Cancer134 (2014), 376-83.
11.
LinH., LinH.X., GeN., WangH.Z., SunR. and HuW.H., Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy, Radiat Oncol8 (2013), 121.
12.
HeinigM. and JohnsonR.J., Role of uric acid in hypertension, renal disease, and metabolic syndrome, Cleve Clin J Med73 (2006), 1059-64.
13.
StotzM., SzkanderaJ., SeidelJ., StojakovicT., SamoniggH., ReitzD., GaryT., KornpratP., Schaberl-MoserR., HoeflerG., GergerA. and PichlerM., Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients, PLoS One9 (2014), e104730.
14.
TanriverdiO., CokmertS., OktayE., PilanciK.N., MenekseS., KocarM., SenC.A., AvciN., AkmanT., OrduC., GokselG. and MeydanN., 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 Oncol31 (2014), 217.
15.
YinJ.Y., TangQ., ZhaiL.L., ZhouL.Y., QianJ., LinJ., WenX.M., ZhouJ.D., ZhangY.Y., ZhuX.W. and DengZ.Q., High expression of OCT4 is frequent and may cause undesirable treatment outcomes in patients with acute myeloid leukemia, Tumour Biol (2015).
16.
HorsfallL.J., NazarethI. and PetersenI., Serum uric acid and the risk of respiratory disease: a population-based cohort study, Thorax69 (2014), 1021-6.
17.
LicklE., AlthG., EbermannR., BeckR.H. and TumaK., Serum urate level and cancer, Med Hypotheses28 (1989), 193-5.
18.
StrasakA.M., LangS., KneibT., BrantL.J., KlenkJ., HilbeW., OberaignerW., RuttmannE., KaltenbachL., ConcinH., DiemG., PfeifferK.P., UlmerH., Vhm and GroupP.P.S., 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 Epidemiol19 (2009), 15-24.
19.
DemirH., AkkusZ.A., CebiA., CakirT. and IzmirliM., Catalase, carbonic anhydrase and other biochemical parameters in esophageal cancers in Turkey, Asian Pac J Cancer Prev11 (2010), 1029-32.
20.
Fernandez-RealJ.M. and PickupJ.C., Innate immunity, insulin resistance and type 2 diabetes, Trends Endocrinol Metab19 (2008), 10-6.
21.
LorinczA.M. and SukumarS., Molecular links between obesity and breast cancer, Endocr Relat Cancer13 (2006), 279-92.
22.
ShiY., EvansJ.E. and RockK.L., Molecular identification of a danger signal that alerts the immune system to dying cells, Nature425 (2003), 516-21.
23.
ShiY., ZhengW. and RockK.L., Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses, Proc Natl Acad Sci U S A97 (2000), 14590-5.
24.
JacksonA.L. and LoebL.A., The contribution of endogenous sources of DNA damage to the multiple mutations in cancer, Mutat Res477 (2001), 7-21.
25.
StorzP., Reactive oxygen species in tumor progression, Front Biosci10 (2005), 1881-96.
26.
CoussensL.M. and WerbZ., Inflammation and cancer, Nature420 (2002), 860-7.
27.
MantovaniA., AllavenaP., SicaA. and BalkwillF., Cancer-related inflammation, Nature454 (2008), 436-44.
28.
LamJ.B., ChowK.H., XuA., LamK.S., LiuJ., WongN.S., MoonR.T., ShepherdP.R., CooperG.J. and WangY., Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities, PLoS One4 (2009), e4968.
29.
LyngdohT., Marques-VidalP., PaccaudF., PreisigM., WaeberG., BochudM. and VollenweiderP., Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study, PLoS One6 (2011), e19901.
30.
SaitoK. and KiharaK., Role of C-reactive protein as a biomarker for renal cell carcinoma, Expert Rev Anticancer Ther10 (2010), 1979-89.
31.
SiemesC., VisserL.E., CoeberghJ.W., SplinterT.A., WittemanJ.C., UitterlindenA.G., HofmanA., PolsH.A. and StrickerB.H., C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study, J Clin Oncol24 (2006), 5216-22.
32.
TsilidisK.K., BranchiniC., GuallarE., HelzlsouerK.J., ErlingerT.P. and PlatzE.A., C-reactive protein and colorectal cancer risk: a systematic review of prospective studies, Int J Cancer123 (2008), 1133-40.
33.
LinderN., HaglundC., LundinM., NordlingS., RistimakiA., KokkolaA., MrenaJ., WikstenJ.P. and LundinJ., Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer, J Clin Pathol59 (2006), 965-71.
34.
LinderN., LundinJ., IsolaJ., LundinM., RaivioK.O. and JoensuuH., Down-regulated xanthine oxidoreductase is a feature of aggressive breast cancer, Clin Cancer Res11 (2005), 4372-81.
35.
FiniM.A., MonksJ., FarabaughS.M. and WrightR.M., Contribution of xanthine oxidoreductase to mammary epithelial and breast cancer cell differentiation in part modulates inhibitor of differentiation-1, Mol Cancer Res9 (2011), 1242-54.
36.
ShinH.S., LeeH.R., LeeD.C., ShimJ.Y., ChoK.H. and SuhS.Y., Uric acid as a prognostic factor for survival time: a prospective cohort study of terminally ill cancer patients, J Pain Symptom Manage31 (2006), 493-501.
37.
DhankharR., DahiyaK., SharmaT.K., GhalautV.S., AtriR. and KaushalV., Diagnostic significance of adenosine deaminase, uric acid and C-reactive protein levels in patients of head and neck carcinoma, Clin Lab57 (2011), 795-8.
