Expression of NSE, CYFRA21-1 and Fer in patients with ovarian cancer and their relationship with lymph node metastasis
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摘要: 目的 探讨卵巢癌(OC)患者神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)、铁蛋白(Fer)表达及与淋巴结转移(LNM)的关系。方法 选取2019年1月1日至2021年12月31日收治的264例OC患者为研究对象，其中176例为训练组创建模型，88例为验证组评判模型，另选取同期卵巢良性肿瘤患者88例为对照Ⅰ组，健康体检者88例为对照Ⅱ组。对比训练组、对照Ⅰ组、对照Ⅱ组血清NSE、CYFRA21-1、Fer水平，多因素非条件logistic回归方程筛选危险因素，并建立方程，通过受试者工作特征(ROC)曲线完成自身验证，K折交叉进行组外验证。结果 训练组血清NSE、CYFRA21-1、Fer水平高于对照Ⅰ组、对照Ⅱ组，对照Ⅰ组血清NSE、CYFRA21-1、Fer水平高于对照Ⅱ组(P < 0.05)；发生LNM患者病灶直径大于无LNM患者，分化程度低于LNM患者，血清NSE、CYFRA21-1、Fer水平高于无LNM患者(P < 0.05)；logistic回归模型校正病灶直径、分化程度后，血清NSE、CYFRA21-1、Fer水平升高仍是发生LNM的独立危险因素(P < 0.05)；三者联合评估LNM的ROC曲线下的面积大于单一指标评估值(P < 0.05)；利用K折交叉验证进行组外验证，以检验模型的稳定性，结果显示，10组训练准确性为0.837±0.030，预测准确性为0.871±0.029。结论 NSE、CYFRA21-1、Fer与OC患者LNM密切相关，三者联合可提高LNM诊断效能，经验证，诊断模型具有良好的准确性和稳定性，有助于临床诊断及治疗方案的决策。
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关键词:
- 卵巢癌 /
- 神经元特异性烯醇化酶 /
- 细胞角蛋白19片段 /
- 铁蛋白
Abstract: Objective To investigate the expression of neuron-specific enolase(NSE), cytokeratin 19 fragment(CYFRA21-1), ferritin(Fer) and their relationship with lymph node metastasis(LNM) in patients with ovarian cancer(OC).Methods A total of 264 OC patients in our hospital from January 1, 2019 to December 31, 2021 were selected as the research objects, of which 176 were used as the training group to create the model, and the other 88 were used as the validation group to judge the model. During the same period, 88 patients with benign ovarian tumors were selected as the control group I, and 88 healthy subjects were selected as the control group II. The levels of serum NSE, CYFRA21-1 and Fer in the training group, control group I and control group II were compared. Multivariate unconditional logistic regression equation was used to screen risk factors, and the equation was established. Self-validation was done by receiver operating characteristic(ROC) curve, and out-of-group validation was done by K-fold crossover.Results The serum levels of NSE, CYFRA21-1 and Fer in the training group were higher than those in the control group I and the control group II, and the serum NSE, CYFRA21-1 and Fer levels in the control group I were higher than those in the control group II(P < 0.05). The diameter of lesions in patients with LNM was larger than that in patients without LNM, the degree of differentiation was lower than that in patients with LNM, and the levels of serum NSE, CYFRA21-1 and Fer were higher than those in patients without LNM(P < 0.05). The AUC of the three combined evaluation of LNM was greater than the evaluation value of a single index(P < 0.05). K-fold cross-validation was used for out-of-group validation to test the stability of the model. The results showed that the training accuracy of 10 groups was 0.837 ± 0.030, and the prediction accuracy was 0.871 ± 0.029.Conclusion NSE, CYFRA21-1 and Fer were closely related to LNM in OC patients. The combination of the three could improve the diagnostic efficiency of LNM. It might have been verified that the diagnostic model has good accuracy and stability, and it might be helpful for clinical diagnosis and decision-making of treatment plans.-
Key words:
- ovarian cancer /
- neuron-specific enolase /
- cytokeratin 19 fragment /
- ferritin
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表 1 3组血清NSE、CYFRA21-1、Fer水平
X±S 组别 例数 NSE/(ng·mL-1) CYFRA21-1/(ng·mL-1) Fer/(μg·L-1) 训练组 176 20.99±3.87 13.27±4.06 248.94±60.89 对照Ⅰ组 88 9.08±1.92 3.15±0.92 114.92±46.20 对照Ⅱ组 88 5.48±1.39 1.54±0.36 50.94±20.18 F 960.163 623.910 522.591 
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表 2 训练组是否发生LNM的OC患者资料比较
例(%)，X±S 因素 LNM(69例) 无LNM(107例) t/χ2 P 年龄/岁 51.26±5.91 52.30±6.83 1.039 0.301 体重指数/(kg·m-2) 22.10±1.34 21.87±1.59 0.995 0.321 不良生活方式 吸烟 3(4.35) 5(4.67) 0.010 0.920 饮酒 5(7.25) 8(7.48) 0.003 0.955 妊娠次数 0.012 0.914 ≤3次 42(60.87) 66(61.68) >3次 27(39.13) 41(38.32) 分娩次数 0.002 0.966 ≤2次 46(66.67) 71(66.36) >2次 23(33.33) 36(33.64) 痛经 0.169 0.681 有 22(31.88) 31(28.97) 无 47(68.12) 76(71.03) 月经规律 0.358 0.550 是 45(65.22) 65(60.75) 否 24(34.78) 42(39.25) 病灶直径 5.907 0.015 ≤5 cm 29(42.03) 65(60.75) >5 cm 40(57.97) 42(39.25) 病理分型 2.455 0.293 浆液性囊腺癌 34(49.28) 40(37.38) 黏液性囊腺癌 23(33.33) 45(42.06) 其他 12(17.39) 22(20.56) 分化程度 4.973 0.026 中低分化 49(71.01) 58(54.21) 高分化 20(28.99) 49(45.79) 肿瘤位置 3.742 0.154 左侧 26(37.68) 45(42.06) 右侧 23(33.33) 44(41.12) 双侧 20(28.99) 18(16.82) NSE/(ng·mL-1) 22.78±4.03 19.84±3.79 4.901 < 0.001 CYFRA21-1/(ng·mL-1) 15.02±4.31 12.14±4.02 4.510 < 0.001 Fer/(ng·mL-1) 275.78±63.84 231.63±57.94 4.741 < 0.001
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表 3 赋值
变量 赋值 因变量 LNM 有=1，无=0 自变量 病灶直径 ≤5 cm=1，>5 cm=2 分化程度 中低分化=1，高分化=2 NSE 具体值 CYFRA21-1 具体值 Fer 具体值
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表 4 LNM的多因素分析
因素 β SE Wald χ2 P OR 95%CI 病灶直径 0.600 0.469 1.635 0.164 1.821 0.569~5.831 分化程度 -0.654 0.417 2.457 0.089 0.520 0.135~2.004 NSE 1.346 0.402 11.205 < 0.001 3.841 2.165~6.813 CYFRA21-1 1.330 0.381 12.189 < 0.001 3.782 2.004~7.136 Fer 1.119 0.369 9.914 0.002 3.061 1.871~5.009 常数项 -32.678
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表 5 Hosmer-Lemeshow检验的随机性
检验次数 总例数 LNM=是 LNM=否 实际观察值 模型期望值 实际观察值 模型期望值 1 76 35 34.68 39 41.32 2 70 28 28.22 42 41.78 3 79 31 30.79 48 48.21 4 94 33 33.35 61 60.65 5 99 42 41.76 57 57.24 6 118 45 45.30 73 72.70 7 98 50 49.68 48 48.32 8 119 34 34.32 85 84.68 9 99 39 39.18 60 59.82 10 121 47 46.59 74 74.41
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表 6 NSE、CYFRA21-1、Fer评估LNM的价值
指标 AUC 95%CI χ2 cut-off值/(μg·L-1) Youden指数 敏感度/% 特异度/% NSE 0.740 0.669~0.803 6.305 >21.31 0.374 71.01 66.36 CYFRA21-1 0.721 0.649~0.786 5.694 >14.03 0.346 57.97 76.64 Fer 0.767 0.697~0.827 7.511 >255.39 0.439 71.01 72.90 联合 0.853 0.791~0.901 12.624 0.626 84.06 78.50
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表 7 K折交叉验证
组号 预测准确性 训练准确性 1 0.821 0.879 2 0.843 0.859 3 0.839 0.878 4 0.902 0.911 5 0.879 0.835 6 0.815 0.811 7 0.824 0.896 8 0.806 0.859 9 0.827 0.903 10 0.809 0.874 X±S 0.837±0.030 0.871±0.029
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[1] 肖伟欢. HE4联合CA72-4、CA19-9血清糖类抗原检测对卵巢癌患者的临床意义[J]. 临床血液学杂志, 2016, 29(10): 808-810. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ201610012.htm
[2] Srivastava AK, Banerjee A, Cui T, et al. Inhibition of miR-328-3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer[J]. Cancer Res, 2019, 79(9): 2314-2326. doi: 10.1158/0008-5472.CAN-18-3668
[3] Liu Y, Fan H, Dong D, et al. Computed tomography-based radiomic model at node level for the prediction of normal-sized lymph node metastasis in cervical cancer[J]. Transl Oncol, 2021, 14(8): 101113. doi: 10.1016/j.tranon.2021.101113
[4] Mao Y, Wang N, Yu F, et al. Simultaneous detection of carcinoembryonic antigen and neuron-specific enolase in human serum based on time-resolved chemiluminescence immunoassay[J]. Analyst, 2019, 144(16): 4813-4819. doi: 10.1039/C9AN00910H
[5] Dai L, Wang C, Song K, et al. Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation[J]. J Ovarian Res, 2021, 14(1): 62. doi: 10.1186/s13048-021-00815-y
[6] 张欣婷, 张歌, 李玲燕. HPV16感染对卵巢癌患者血清中癌抗原125、铁蛋白和WNT5B蛋白水平的影响[J]. 国际病毒学杂志, 2019, (3): 185-187. doi: 10.3760/cma.j.issn.1673-4092.2019.03.012
[7] 李静, 雷俊梅, 金亮亮, 等. 曲妥珠单抗联合多西他赛化疗对HER2阳性晚期乳腺癌患者血清铁蛋白、IL-6、IL-8、IL-10表达及甲状腺功能的影响[J]. 中国临床药学杂志, 2020, 29(4): 257-261. https://www.cnki.com.cn/Article/CJFDTOTAL-LCZZ202004005.htm
[8] Prat J, FIGO Committee on Gynecologic Oncology. FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication[J]. J Gynecol Oncol, 2015, 26(2): 87-89. doi: 10.3802/jgo.2015.26.2.87
[9] Biggs WS, Marks ST. Diagnosis and Management of Adnexal Masses[J]. Am Fam Physician, 2016, 93(8): 676-681.
[10] Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review[J]. Semin Oncol Nurs, 2019, 35(2): 151-156. doi: 10.1016/j.soncn.2019.02.001
[11] Gardner AB, Charo LM, Mann AK, et al. Ovarian, uterine, and cervical cancer patients with distant metastases at diagnosis: most common locations and outcomes[J]. Clin Exp Metastasis, 2020, 37(1): 107-113. doi: 10.1007/s10585-019-10007-0
[12] van Veenendaal LM, van Akkooi A. ASO Author Reflections: Neuron-Specific Enolase as a Valuable Biomarker for Patients with Merkel Cell Carcinoma in the Era of Immunotherapy[J]. Ann Surg Oncol, 2020, 27(Suppl 3): 769-770.
[13] Banh RS, Biancur DE, Yamamoto K, et al. Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer[J]. Cell, 2020, 183(5): 1202-1218. doi: 10.1016/j.cell.2020.10.016
[14] Hu K, Cheng J, Li J, et al. Perfluorosulfonic acid polymer based eATRP for ultrasensitive detection of CYFRA21-1 DNA[J]. Anal Methods, 2020, 12(22): 2827-2834. doi: 10.1039/D0AY00328J
[15] 祁慧兰, 李鑫, 王春兰. 血清NSE、TSGF、FERR及CA125联合检测对卵巢癌的诊断价值[J]. 临床与病理杂志, 2021, 41(10): 2254-2259. doi: 10.3978/j.issn.2095-6959.2021.10.005
[16] Rudhart SA, Schultz JD, Gehrt F, et al. CYFRA 21-1: a suitable tumor marker in patients with head and neck cutaneous squamous cell carcinoma?[J]. Eur Arch Otorhinolaryngol, 2019, 276(12): 3467-3475. doi: 10.1007/s00405-019-05614-2
[17] Luo H, Shen K, Li B, et al. Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer[J]. Oncol Lett, 2020, 20(1): 742-750. doi: 10.3892/ol.2020.11633
[18] Kahn BM, Lucas A, Alur RG, et al. The vascular landscape of human cancer[J]. J Clin Invest, 2021, 131(2): e136655. doi: 10.1172/JCI136655
[19] Ayuso JM, Virumbrales-Munoz M, McMinn PH, et al. Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients[J]. Lab Chip, 2019, 19(20): 3461-3471. doi: 10.1039/C9LC00270G
[20] Ye J, Wang Z, Chen X, et al. YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation[J]. Theranostics, 2020, 10(26): 12072-12089. doi: 10.7150/thno.51231
[21] Adameyko KI, Burakov AV, Finoshin AD, et al. Conservative and Atypical Ferritins of Sponges[J]. Int J Mol Sci, 2021, 22(16): 8635. doi: 10.3390/ijms22168635
[22] Moroz V, Machin D, Hero B, et al. The prognostic strength of serum LDH and serum ferritin in children with neuroblastoma: A report from the International Neuroblastoma Risk Group(INRG) project[J]. Pediatr Blood Cancer, 2020, 67(8): e28359.
[23] Collins JF. A Synthetic Ferritin Core Analog Functions as a Next-Generation Iron Supplement[J]. J Nutr, 2022, 152(3): 651-652. doi: 10.1093/jn/nxab436
[24] Li Z, Liu J, Chen H, et al. Ferritin Light Chain(FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer[J]. Carcinogenesis, 2020, 41(4): 467-477.
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