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北京大学学报（医学版） ›› 2021, Vol. 53 ›› Issue (4): 647-652. doi: 10.19723/j.issn.1671-167X.2021.04.004

• 论著 • 上一篇    下一篇

术前血小板参数与局部进展期肾细胞癌预后

肖若陶,刘承,徐楚潇,何为,马潞林()   

  1. 北京大学第三医院泌尿外科,北京 100191
  • 收稿日期:2021-03-10 出版日期:2021-08-18 发布日期:2021-08-25
  • 通讯作者: 马潞林 E-mail:malulin@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81972381)

Prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma

XIAO Ruo-tao,LIU Cheng,XU Chu-xiao,HE Wei,MA Lu-lin()   

  1. Department of Urology, Peking University Third Hospital, Beijing 100191, China
  • Received:2021-03-10 Online:2021-08-18 Published:2021-08-25
  • Contact: Lu-lin MA E-mail:malulin@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81972381)

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摘要：

目的: 探讨术前血小板参数对局部进展期肾癌预后的预测价值,为此类患者的危险分层提供参考。方法: 选择北京大学第三医院2015年1月—2017年12月局部进展期肾癌患者进行回顾性分析,依据随访过程中肿瘤是否复发或转移分成进展组和无进展组,比较两组术前血小板参数和临床资料的差异。通过受试者特征工作曲线(receiver operating characteristic curve, ROC)确定血小板参数的最佳临界值,Kaplan-Meier生存曲线分析不同血小板参数与疾病无进展生存时间(progression-free survival, PFS)的关系。通过Cox比例风险模型进行多因素分析确定PFS的独立危险因素。采用时间依赖ROC、净重新分类指数(net reclassification index, NRI)和综合判别改善指数(integrated discrimination improvement, IDI)评估纳入血小板参数后对SSIGN模型改良情况。结果: 共有215例患者入选本研究,其中192例(89.3%)患者获得随访,中位随访时间为36个月。64例(29.8%)患者随访过程中出现疾病进展,中位PFS为46个月。进展组患者的血小板数量(platelet count, PLT)相较无进展组高[(250.72±88.59)×109/L vs. (227.27±66.94)×109/L, P=0.042],血小板分布宽度(platelet distribution width, PDW)相较无进展组低[(12.01±2.27)% vs. (13.31±2.74)%, P=0.001]。将285×109/L及12.65%作为PLT及PDW的最佳临界值,PLT≤285×109/L组患者中位PFS显著长于PLT>285×109/L组(53个月vs. 41个月,P=0.033);PDW>12.65%组患者中位PFS也显著长于PDW≤12.65%组(56个月vs. 41个月,P<0.001)。多因素分析显示术前PDW(HR=0.735, P<0.001)、细胞核分级Ⅲ~Ⅳ级(HR=2.425, P=0.001)、合并肉瘤样分化(HR=3.101, P=0.008)为PFS的独立危险因素。术前PDW联合SSIGN预后评分模型曲线下面积大于原有SSIGN模型[0.748 (95%CI:0.662~0.833) vs. 0.678 (95%CI: 0.583~0.773), P=0.193],NRI为0.262(P=0.04),IDI为 0.085(P=0.01),表明PDW纳入SSIGN模型后其预测能力提高。结论: 术前高PLT和低PDW与局部进展期肾癌不良预后相关,其中PDW是患者预后的独立危险因素,因此,术前PDW有助于对局部进展期肾癌进行危险分层。

关键词: 肾癌, 局部进展期, 血小板, 预后

Abstract:

Objective: To explore the prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma for the risk stratification of such patients. Methods: Clinical data of patients with locally advanced renal cell carcinoma in the Third Hospital of Peking University from January 2015 to December 2017 were collected. The patients were divided into progression group and progression-free group according to follow-up data, and preoperative platelet parameters and clinical data between the two groups were compared. The optimal cut-off value of platelet parameters was determined by receiver operating characteristic curve (ROC) and analyzed by Kaplan-Meier survival curve. Cox proportional hazards model was used to analyze the independent risk factors of PFS. Time dependent ROC curve, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the improvement of SSIGN model by incorporating platelet parameters. Results: Of the 215 patients, 192 (89.3%) were followed up for a median of 36 months. Sixty-four patients (29.8%) had disease progression during the follow-up, and the median PFS was 46 months. In progression group, the platelet count (PLT) was higher [(250.72 ± 88.59)×109/L vs. (227.27 ± 66.94)×109/L, P=0.042] and the platelet distribution width (PDW) was lower [(12.01 ± 2.27)% vs. (13.31 ± 2.74)%, P = 0.001] than that of progression-free groups. 285×109 /L and 12.65% as the best cut-off values of PLT and PDW, the median PFS of PLT≤285×109 /L group was significantly longer than that of PLT>285×109 /L group (53 months vs. 41 months, P=0.033), and the median PFS of PDW>12.65% group was also significantly longer than that of PDW≤12.65% group (56 months vs. 41 months, P<0.001). Multivariate analysis showed that preoperative PDW (HR=0.735, P<0.001), nuclear grade Ⅲ to Ⅳ (HR=2.425, P=0.001) and sarcomatoid differentiation (HR=3.101, P=0.008) were independent risk factors for PFS. The area under the curve of PDW combined with SSIGN model was larger than that with the original SSIGN model [0.748 (95%CI:0.662-0.833) vs. 0.678 (95%CI: 0.583-0.773), P=0.193], NRI was 0.262 (P=0.04), and IDI was 0.085 (P=0.01), indicating that the predictive ability of PDW combined with SSIGN model was improved. Conclusion: Preoperative high PLT and low PDW are associated with adverse prognosis of locally advanced renal cell carcinoma, and PDW is an independent risk factor. Therefore, preoperative PDW could serve as biomarker for risk stratification of locally advanced renal cell carcinoma.

Key words: Renal cell carcinoma, Locally advanced, Platelet, Prognosis

中图分类号: 

  • R737.11

表1

患者临床组织病理学资料及与疾病进展相关单因素分析"

Characteristics Progression free
(n=128, 66.7%)		 Progression
(n=64, 33.3%)		 P
Age/years, $\bar{x}±s$ 59.8±12.7 58.6±8.6 0.490
Gender, n(%)
Male 87 (68) 46 (71.9) 0.622
Female 41 (32) 18 (28.1)
Symptom at presentation, n(%) 35 (27.3) 38 (59.4) <0.001*
BMI/(kg/m2), $\bar{x}±s$ 25.4±3.5 24.7±3.3 0.135
Comorbidities, n(%)
Hypertension 54 (42.2) 29 (45.3) 0.758
Diabetes mellitus 26 (20.3) 6 (9.4) 0.065
Surgical approach, n(%)
Open 50 (39.1) 29 (45.3) 0.439
Laparoscopic 78 (60.9) 35 (54.7)
Surgical time/min, $\bar{x}±s$ 193.60±94.03 276.23±130.14 <0.001
Interoperative blood loss/mL, $\bar{x}±s$ 359.53±951.83 711.72±1 063.19 0.027
Tumor side, n(%) 1.000
Left 69 (53.9) 34 (53.1)
Right 59 (46.1) 30 (46.9)
Tumor size/cm, $\bar{x}±s$ 6.6±3.7 7.1±2.8 0.345
Histologic subtype, n(%) 0.649
CCRCC 113 (88.3) 55 (85.9)
Non-CCRCC 15 (11.7) 9 (14.1)
Nuclear grade, n(%) <0.001*
Ⅰ to Ⅱ 86 (67.2) 27 (42.2)
Ⅲ to Ⅳ 32 (25) 36 (56.3)
Unknow 10 (7.8) 1 (1.6)
Necrosis, n(%) 27 (21.1) 33 (51.6) <0.001*
Sarcomatoid differentiation, n(%) 4 (3.1) 7 (10.9) 0.044*
Rheumatoid differentiation, n(%) 5 (3.9) 5 (7.8) 0.305
Lymphovascular invasion, n(%) 14 (10.9) 17 (26.6) 0.011*
Renal sinus invasion, n(%) 95 (74.2) 47 (73.4) 1.000
Perirenal fat invasion, n(%) 30 (23.4) 23 (35.9) 0.087
Urinary collecting system invasion, n(%) 3 (2.3) 5 (7.8) 0.120
Venous tumor thrombus, n(%) 37 (28.9) 38 (59.4) <0.001*
Lymph node invasion, n(%) 2 (1.6) 6 (9.4) 0.018*
Adrenal invasion, n(%) 4 (3.1) 6 (9.4) 0.086
SSIGN score, n(%) 0.013
0-3 46 (35.9) 12 (18.8)
4-6 73 (57) 41 (64.1)
7-11 9 (7) 11 (17.2)
Platelet indices
PLT/(×109/L), $\bar{x}±s$ 227.27±66.94 250.72±88.59 0.042*
MPV/fL, $\bar{x}±s$ 10.12±1.26 9.96±0.97 0.394
PDW/%, $\bar{x}±s$ 13.31±2.74 12.01±2.27 0.001*

图1

Kaplan-Meier法绘制患者在术前不同水平PLT(A)和PDW(B)的肾癌无进展生存曲线"

表2

肾癌术后发生进展Cox比例风险模型多因素分析"

Items B SE Wald P Exp(B) (95%CI)
Nuclear grade
Ⅰ to Ⅱ Ref - - - -
Ⅲ to Ⅳ 0.886 0.275 10.343 0.001 2.425 (1.413-4.161)
Unknow -0.984 1.021 0.929 0.335 0.374 (0.051-2.764)
Sarcomatoid differentiation 1.132 0.428 6.999 0.008 3.101 (1.341-7.170)
PDW* -0.308 0.067 20.884 <0.001 0.735 (0.644-0.839)

图2

时间依赖ROC曲线评估术前PDW联合SSIGN预后评分模型对原有模型改良情况"

[1] Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis [J]. Nat Rev Cancer, 2011, 11(2):123-134.
doi: 10.1038/nrc3004
[2] 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 pmid: 22094253
[3] Nieswandt B, Hafner M, Echtenacher B, et al. Lysis of tumor cells by natural killer cells in mice is impeded by platelets [J]. Cancer Res, 1999, 59(6):1295-1300.
pmid: 10096562
[4] Zhu X, Cao Y, Lu P, et al. Evaluation of platelet indices as diagnostic biomarkers for colorectal cancer [J]. Sci Rep, 2018, 8(1):11814.
doi: 10.1038/s41598-018-29293-x
[5] Liu C, Zhang H, Qi Q, et al. The preoperative platelet distribution width: A predictive factor of the prognosis in patients with non-small cell lung cancer [J]. Thorac Cancer, 2020, 11(4):918-927.
doi: 10.1111/tca.v11.4
[6] Liu S, Fang J, Jiao D, et al. Elevated platelet count predicts poor prognosis in breast cancer patients with supraclavicular lymph node metastasis [J]. Cancer Manag Res, 2020, 12(6):6069-6075.
doi: 10.2147/CMAR.S257727
[7] Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the international metastatic renal-cell carcinoma database consortium prognostic model: a population-based study [J]. Lancet Oncol, 2013, 14(2):141-148.
doi: 10.1016/S1470-2045(12)70559-4
[8] Choi JY, Ko YH, Song PH. Clinical significance of preoperative thrombocytosis in patients who underwent radical nephrectomy for nonmetastatic renal cell carcinoma [J]. Investig Clin Urol, 2016, 57(5):324-329.
doi: 10.4111/icu.2016.57.5.324
[9] Seles M, Posch F, Pichler GP, et al. Blood platelet volume represents a novel prognostic factor in patients with nonmetastatic renal cell carcinoma and improves the predictive ability of established prognostic scores [J]. J Urol, 2017, 198(6):1247-1252.
doi: 10.1016/j.juro.2017.07.036
[10] Karakiewicz PI, Trinh QD, Lam JS, et al. Platelet count and preoperative haemoglobin do not significantly increase the performance of established predictors of renal cell carcinoma-specific mortality [J]. Eur Urol, 2007, 52(5):1428-1436.
pmid: 17420085
[11] Frank I, Blute ML, Cheville JC, et al. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score [J]. J Urol, 2002, 168(6):2395-2400.
doi: 10.1016/S0022-5347(05)64153-5
[12] Zisman A, Pantuck AJ, Dorey F, et al. Improved prognostication of renal cell carcinoma using an integrated staging system [J]. J Clin Oncol, 2001, 19(6):1649-1657.
pmid: 11250993
[13] Amin MB, Edge SB, Greene FL, et al. AJCC cancer staging manual[M]. 8th ed. Chicago: Springer, 2017: 739-747.
[14] Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update [J]. Eur Urol, 2015, 67(5):913-924.
doi: 10.1016/j.eururo.2015.01.005 pmid: 25616710
[15] Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours [J]. Eur Urol, 2016, 70(1):93-105.
doi: 10.1016/j.eururo.2016.02.029
[16] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021 [J]. CA Cancer J Clin, 2021, 71(1):7-33.
doi: 10.3322/caac.v71.1
[17] Haas NB, Manola J, Dutcher JP, et al. Adjuvant treatment for high-risk clear cell renal cancer: updated results of a high-risk subset of the ASSURE randomized trial [J]. JAMA Oncol, 2017, 3(9):1249-1252.
doi: 10.1001/jamaoncol.2017.0076
[18] Motzer RJ, Haas NB, Donskov F, et al. Randomized phase Ⅲ trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma [J]. J Clin Oncol, 2017, 35(35):3916-3923.
doi: 10.1200/JCO.2017.73.5324
[19] Motzer RJ, Ravaud A, Patard JJ, et al. Adjuvant sunitinib for high-risk renal cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results [J]. Eur Urol, 2018, 73(1):62-68.
doi: 10.1016/j.eururo.2017.09.008
[20] Leibovich BC, Blute ML, Cheville JC, et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials [J]. Cancer, 2003, 97(7):1663-1671.
pmid: 12655523
[21] Karakiewicz PI, Briganti A, Chun FK, et al. Multi-institutional validation of a new renal cancer-specific survival nomogram [J]. J Clin Oncol, 2007, 25(11):1316-1322.
pmid: 17416852
[22] Correa AF, Jegede O, Haas NB, et al. Predicting renal cancer recurrence: defining limitations of existing prognostic models with prospective trial-based validation [J]. J Clin Oncol, 2019, 37(23):2062-2071.
doi: 10.1200/JCO.19.00107
[23] Xiao R, Xu C, He W, et al. Preoperative anaemia and thrombocytosis predict adverse prognosis in non-metastatic renal cell carcinoma with tumour thrombus [J]. BMC Urol, 2021, 21(1):31.
doi: 10.1186/s12894-021-00796-6
[24] Yue CX, Liu YX, Yun ZY, et al. Decreased platelet distribution width predicts a worse prognosis in patients undergoing surgical resection for hepatocellular carcinoma [J]. Cancer Biomark, 2019, 26(3):361-366.
doi: 10.3233/CBM-190474
[25] Chen H, Wu Q, Zhang Y, et al. Nomograms based on the novel platelet index score predict postoperative prognosis in endometrial cancer [J]. Gynecol Oncol, 2020, 158(3):689-697.
doi: S0090-8258(20)31125-2 pmid: 32507649
[26] Kawakita Y, Motoyama S, Sato Y, et al. Prognostic significance of combined platelet distribution width and C-reactive protein score in esophageal cancer [J]. Anticancer Res, 2020, 40(10):5715-5725.
doi: 10.21873/anticanres.14586 pmid: 32988897
[27] 蒋慧云, 李小毛, 王佳, 等. 术前血小板分布宽度在子宫内膜癌诊断预测中的价值 [J]. 实用医学杂志, 2018, 34(7):1188-1190.
[28] Vagdatli E, Gounari E, Lazaridou E, et al. Platelet distribution width: a simple, practical and specific marker of activation of coagulation [J]. Hippokratia, 2010, 14(1):28-32.
pmid: 20411056
[29] 张翔, 庄瑞. 血小板分布宽度对鼻咽癌患者预后的影响 [J]. 国际肿瘤学杂志, 2018, 45(5):257-261.
[30] Huang Y, Cui MM, Huang YX, et al. Preoperative platelet distribution width predicts breast cancer survival [J]. Cancer Biomark, 2018, 23(2):205-211.
doi: 10.3233/CBM-181267 pmid: 30198864
[31] 张林楠, 刘玉峰, 苏淑芳, 等. 血小板分布宽度对神经母细胞瘤预后的预测价值 [J]. 中华实用儿科临床杂志, 2020, 35(6):440-444.
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