A study on the interaction effect of platelet count and sex on prognosis in patients with esophageal squamous cell carcinoma after esophagectomy
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摘要:
目的 探讨血小板(platelets, PLT)对食管鳞癌(esophageal squamous cell carcinoma, ESCC)根治术患者预后的影响及其与性别、年龄间的交互作用。 方法 选取2014年2月1日―2018年11月30日582例符合入组标准的ESCC患者进行回顾性分析。Kaplan-Meier法用于绘制生存曲线并行log-rank检验。运用Cox比例风险回归模型进行多因素分析,计算总生存时间(overall survival, OS)、无病生存时间(disease free survival, DFS)的危险系数(hazard ratios, HR)及其95% CI。 结果 PLT仅与性别存在交互作用(HR=2.417, 95% CI: 1.150~5.078, P=0.018)。分层分析显示,男性PLT增多组的死亡风险是PLT正常组的1.713倍(HR=1.713, 95% CI: 1.203~2.441, P=0.003);女性PLT增多组与PLT正常组预后差异无统计学意义(HR=0.590, 95% CI: 0.299~1.165, P=0.129)。 结论 PLT与性别对ESCC根治术患者预后的预测存在交互作用,采用PLT预测患者预后时应注意性别的差异。 Abstract:Objective To investigate the prognostic value of the preoperative platelet count (PLT) and its interactions with gender and age in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. Methods A total of 582 patients with ESCC were eligible for retrospective analysis between February 1, 2014, and November 30, 2018. The survival rate was calculated using the Kaplan-Meier method and the comparison of the two groups was performed by using the Log-rank test. Univariate and multivariate analyses were calculated using the Cox proportional hazards regression model to determine prognostic factors associated with overall survival (OS) and disease-free survival(DFS). Hazard ratios (HRs) and (95% CI) were used as common measures to assess relative risk. Results PLT only interacted with gender (HR=2.417, 95% CI: 1.150-5.078, P=0.018). Stratified analysis showed that PLT increased group was independently associated with a 71.3% risk increase for death compared with PLT normal group (HR=1.713, 95% CI: 1.203-2.441, P=0.003) in male patients; While in female patients, there was no statistical significance between groups (HR=0.590, 95% CI: 0.299-1.165, P=0.129). Conclusions There is an interaction between PLT and gender in predicting the prognosis of patients with ESCC after esophagectomy. Gender differences should be paid attention to when PLT is chosen to be a prognostic factor. -
Key words:
- Esophageal squamous cell carcinoma /
- Platelet count /
- Prognosis /
- Gender /
- Interaction
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表 1 582例ESCC患者临床特征[n(%)]
Table 1. Clinical characteristics of 582 cases of ESCC [n(%)]
变量 合计
(N=582)福建医科大学附属第一医院
(n=211)福建省肿瘤医院
(n=371)χ2值 P值 变量 合计
(N=582)福建医科大学附属第一医院
(n=211)福建省肿瘤医院
(n=371)χ2值 P值 性别 0.830 0.362 TNM分期 2.332 0.312 女 145(24.9) 48(22.7) 97(26.1) Ⅰ~Ⅱ 296(50.9) 104(49.3) 192(51.8) 男 437(75.1) 163(77.3) 274(73.9) Ⅲ~Ⅳ 275(47.3) 105(49.8) 170(45.8) 年龄(岁) 0.326 0.568 缺失 11(1.9) 2(0.9) 9(2.4) < 60 242(41.6) 91(43.1) 151(40.7) PNI 6.268 0.044 ≥60 340(58.4) 120(56.9) 220(59.3) ≤49.9 293(50.3) 103(48.8) 190(51.2) 肿瘤部位 14.720 0.001 >49.9 286(49.1) 105(49.8) 181(48.8) 胸上段 72(12.4) 28(13.3) 44(11.9) 缺失 3(0.5) 3(1.4) 0(0.0) 胸中段 310(53.3) 131(62.1) 179(48.2) PLT(×109/L) 0.227 0.634 胸下段 200(34.4) 52(24.6) 148(39.9) 100~300 464(79.7) 166(78.7) 298(80.3) 肿瘤最长径(cm) 0.362 0.834 >300 118(20.3) 45(21.3) 73(19.7) ≤4 364(62.5) 129(61.1) 235(63.3) 术后辅助治疗 0.619 0.431 >4 211(36.3) 79(37.4) 132(35.6) 否 349(60.0) 131(62.1) 218(58.8) 缺失 7(1.2) 3(1.4) 4(1.1) 是 233(40.0) 80(37.9) 153(41.2) 表 2 PLT与ESCC患者临床特征间的关系[n(%)]
Table 2. Association between PLT and clinical characteristics of ESCC patients [n(%)]
变量 PLT(×109/L) χ2值 P值 变量 PLT(×109/L) χ2值 P值 100~300(n=464) >300(n=118) 100~300(n=464) >300(n=118) 性别 0.327 0.567 PNI 2.310 0.315 女 118(25.4) 27(22.9) ≤49.9 238(51.3) 55(46.6) 男 346(74.6) 91(77.1) >49.9 223(48.1) 63(53.4) 年龄(岁) 0.377 0.539 缺失 3(0.6) 0(0.0) < 60 190(40.9) 52(44.1) TNM分期 4.168 0.124 ≥60 274(59.1) 66(55.9) Ⅰ~Ⅱ 241(51.9) 55(46.6) 肿瘤部位 7.791 0.020 Ⅲ~Ⅳ 217(46.8) 58(49.2) 胸上段 65(14.0) 7(5.9) 缺失 6(1.3) 5(4.2) 胸中段 249(53.7) 61(51.7) 术后辅助治疗 0.337 0.561 胸下段 150(32.3) 50(42.2) 否 281(60.6) 68(57.6) 肿瘤最长径(cm) 26.116 < 0.001 是 183(39.4) 50(42.4) ≤4 312(67.2) 52(44.1) >4 145(31.3) 66(55.9) 缺失 7(1.5) 0(0.0) -
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. [2] Lin Y, Totsuka Y, He Y, et al. Epidemiology of esophageal cancer in Japan and China[J]. J Epidemiol, 2013, 23(4): 233-242. DOI: 10.2188/jea.je20120162. [3] Rachidi S, Kaur M, Lautenschlaeger T, et al. Platelet count correlates with stage and predicts survival in melanoma[J]. Platelets, 2019, 30(8): 1042-1046. DOI: 10.1080/09537104.2019.1572879. [4] Sylman JL, Boyce HB, Mitrugno A, et al. A temporal examination of platelet counts as a predictor of prognosis in lung, prostate, and colon cancer patients[J]. Sci Rep, 2018, 8(1): 6564-6569. DOI: 10.1038/s41598-018-25019-1. [5] Rachidi S, Li H, Wallace K, et al. Preoperative platelet counts and postoperative outcomes in cancer surgery: a multicenter, retrospective cohort study[J]. Platelets, 2020, 31(1): 79-87. DOI: 10.1080/09537104.2019.1573977. [6] Feng JF, Huang Y, Lu WS, et al. Preoperative platelet count in esophageal squamous cell carcinoma: is it a prognostic factor?[J]. Langenbecks Arch Surg, 2013, 398(8): 1115-1122. DOI: 10.1007/s00423-013-1111-4. [7] Shimada H, Oohira G, Okazumi S, et al. Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma[J]. J Am Coll Surg, 2004, 198(5): 737-741. DOI: 10.1016/j.jamcollsurg.2004.01.022. [8] 李小江, 沈艳辉, 崔庆贵. 术前血小板增多与食管鳞癌患者预后的相关性分析[J]. 临床荟萃, 2015, 30(4): 408-411, 415. DOI: 10.3969/j.issn.1004-583X.2015.04.013.Li XJ, Shen YH, Cui QG. Association of preoperative thrombocytosis with prognosis of patients with esophageal squamous cell carcinoma after surgical resection[J]. Clin Focus, 2015, 30(4): 408-411, 415. DOI: 10.3969/j.issn.1004-583X.2015.04.013. [9] 许鹏, 雷畅, 张兆卿, 等. 食管鳞癌患者高血小板血症与预后关系分析[J]. 医学与哲学, 2009, 30(16): 27-28, 36. https://www.cnki.com.cn/Article/CJFDTOTAL-YXZL200908014.htmXu P, Lei C, Zhang ZQ, et al. The prognostic significance of thrombocytosis in patients with esophageal squamous cell carcinomas[J]. Med Philosophy, 2009, 30(16): 27-28, 36. https://www.cnki.com.cn/Article/CJFDTOTAL-YXZL200908014.htm [10] Wang J, Liu H, Shao N, et al. The clinical significance of preoperative plasma fibrinogen level and platelet count in resectable esophageal squamous cell carcinoma[J]. World J Surg Oncol, 2015, 13: 157-163. DOI: 10.1186/s12957-015-0543-4. [11] 乔呈瑞, 赵松, 李向楠, 等. 外周血纤维蛋白原及血小板与食管鳞癌临床病理特征及其预后的相关性[J]. 中国老年学杂志, 2016, 36(2): 348-350. DOI: 10.3969/j.issn.1005-9202.2016.02.043.Qiao CR, Zhao S, Li XN, et al. Association of peripheral blood fibrinogen and platelets with clinicopathological characteristics and prognosis of esophageal squamous cell carcinoma[J]. Chin J Gerontol, 2016, 36(2): 348-350. DOI: 10.3969/j.issn.1005-9202.2016.02.043. [12] Santimone I, Di Castelnuovo A, De Curtis A, et al. White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population: results from the MOLI-SANI project[J]. Haematologica, 2011, 96(8): 1180-1188. DOI: 10.3324/haematol.2011.043042. [13] Biino G, Gasparini P, D'Adamo P, et al. Influence of age, sex and ethnicity on platelet count in five Italian geographic isolates: mild thrombocytopenia may be physiological[J]. Br J Haematol, 2012, 157(3): 384-387. DOI: 10.1111/j.1365-2141.2011.08981.x. [14] 陈文彬, 潘祥林. 诊断学[M]. 第8版. 北京: 人民卫生出版社, 2015: 254-255.Chen WB, Pan XL. Diagnostics[M]. 8th ed. Beijing: People's Medical Publishing House, 2015: 254-255. [15] Haemmerle M, Stone RL, Menter DG, et al. The platelet lifeline to cancer: challenges and opportunities[J]. Cancer Cell, 2018, 33(6): 965-983. DOI: 10.1016/j.ccell.2018.03.002. [16] Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis[J]. Cancer Cell, 2011, 20(5): 576-590. DOI: 10.1016/j.ccr.2011.09.009. [17] Sharma D, Brummel-Ziedins KE, Bouchard BA, et al. Platelets in tumor progression: a host factor that offers multiple potential targets in the treatment of cancer[J]. J Cell Physiol, 2014, 229(8): 1005-1015. DOI: 10.1002/jcp.24539. [18] 刘春花, 巩平, 杨杰. 肺癌患者外周血中循环肿瘤细胞与D-二聚体纤维蛋白原及血小板的关系[J]. 中华肿瘤杂志, 2016, 38(5): 368-371. DOI: 10.3760/cma.j.issn.0253-3766.2016.05.009.Liu CH, Gong P, Yang J. Relationship between circulating tumor cells and coagulation factors in primary lung cancer patients[J]. Chin J Oncol, 2016, 38(5): 368-371. DOI: 10.3760/cma.j.issn.0253-3766.2016.05.009. [19] Li R, Ren M, Chen N, et al. Presence of intratumoral platelets is associated with tumor vessel structure and metastasis[J]. BMC Cancer, 2014, 14: 167-174. DOI: 10.1186/1471-2407-14-167. [20] 丛玉隆, 金大鸣, 王鸿利, 等. 中国人群血小板各项参数的调查分析[J]. 中华检验医学杂志, 2004, 27(6): 368-370. DOI: 10.3760/j:issn:1009-9158.2004.06.013.Cong YL, Jin DM, Wang HL, et al. Investigating Chinese platelet parameter in vein blood[J]. Chin J Lab Med, 2004, 27(6): 368-370. DOI: 10.3760/j:issn:1009-9158.2004.06.013. [21] 魏琪, 石晓东, 陶育纯, 等. 中国东北成人血小板参考值的再评价及其影响因素[J]. 中国老年学杂志, 2011, 31(13): 2398-2400. DOI: 10.3969/j.issn.1005-9202.2011.13.003.Wei Q, Shi XD, Tao YC, et al. Re-evaluation of adult platelet reference value in northeast China and its influencing factors[J]. Chin J Gerontol, 2011, 31(13): 2398-2400. DOI: 10.3969/j.issn.1005-9202.2011.13.003. [22] 伍绍国. 广州地区1 883例健康成人静脉血血小板参数参考范围调查[J]. 临床检验杂志, 2005, 23(4): 317-318. DOI: 10.3969/j.issn.1001-764X.2005.04.042.Wu SG. Investigation on the reference range of platelet parameters of venous blood in 1883 healthy adults in Guangzhou[J]. J Clin Lab Sci, 2005, 23(4): 317-318. DOI: 10.3969/j.issn.1001764X.2005.04.042. [23] Gasperi V, Catani MV, Savini I. Platelet responses in cardiovascular disease: sex-related differences in nutritional and pharmacological interventions[J]. Cardiovasc Ther, 2020, 2020: 2342837. DOI: 10.1155/2020/2342837. [24] Soo Kim B, Auerbach DS, Sadhra H, et al. Sex-specific platelet activation through protease-activated receptors reverses in myocardial infarction[J]. Arterioscler Thromb Vasc Biol, 2021, 41(1): 390-400. DOI: 10.1161/ATVBAHA.120.315033. [25] Sarma A, O'Donoghue ML. Conundrums of platelet function testing: does sex matter?[J]. Circ Cardiovasc Interv, 2017, 10(2): e004872. DOI: 10.1161/CIRCINTERVENTIONS.117.004872. [26] Geppert J, Min Y, Neville M, et al. Gender-specific fatty acid profiles in platelet phosphatidyl-choline and ethanolamine[J]. Prostaglandins Leukot Essent Fatty Acids, 2010, 82(1): 51-56. DOI: 10.1016/j.plefa.2009.09.002. [27] Larson MK, Tormoen GW, Weaver LJ, et al. Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation[J]. Am J Physiol Cell Physiol, 2013, 304(3): C273-C279. DOI: 10.1152/ajpcell.00174.2012. [28] Adili R, Hawley M, Holinstat M. Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids[J]. Prostaglandins Other Lipid Mediat, 2018, 139: 10-18. DOI: 10.1016/j.prostaglandins.2018.09.005. [29] Chan MV, Chen MH, Barwari T, et al. Platelet reactivity in individuals over 65 years old is not modulated by age[J]. Circ Res, 2020, 127(3): 394-396. DOI: 10.1161/CIRCRESAHA.119.316324.