半胱氨酸蛋白酶抑制剂4在胰腺癌临床诊断及预后评估中的价值

doi:10.3969/j.issn.1004-616x.2024.06.007

摘要/Abstract

摘要： 目的： 分析血清半胱氨酸蛋白酶抑制剂4(CST4)表达水平在胰腺癌临床诊断及预后评估中的价值。方法： 收集2020年10月—2023年1月就诊于河北医科大学第四医院的71例胰腺癌初诊患者，分别收集患者血常规、凝血功能、血生化及血清肿瘤标记物等指标检测结果及病例信息。分析胰腺癌患者与胰腺良性肿瘤患者血清CST4表达水平及其他临床实验室检测结果的差异，并制作受试者工作特征(ROC)曲线评价CST4在胰腺癌诊断及临床进展评估中的意义。绘制Kaplan-Meier生存曲线并采用多因素Cox回归分析比较CST4与传统肿瘤标记物癌胚抗原(CEA)和糖类抗原199(CA19-9)在胰腺癌临床预后评估中的价值。结果： 与胰腺良性肿瘤对照相比，胰腺癌患者血清CST4、CEA及CA19-9含量异常的比例及中位值均明显升高(P<0.01)。ROC分析显示，CST4在胰腺癌诊断中的曲线下面积(AUC)为0.782，其与CEA和CA19-9联合检测AUC(AUC=0.930)较单项检测明显升高(P<0.05)；而CST4在预测胰腺癌临床进展中显示出更高的价值(AUC=0.794)，敏感度为80.90%，特异性为70.80%，阳性似然比为2.77，最佳截断值为84.41 U/mL；预后分析显示，CST4高表达组和CST4低表达组患者中位生存时间分别为6.2月和25.6月，差异有统计学意义(P<0.01)；血清CST4表达水平升高是胰腺癌患者预后的独立危险因素(P<0.05)。结论： 血清CST4表达水平可作为胰腺癌患者临床辅助诊断指标，是胰腺癌患者预后的独立危险因素。

关键词: 胰腺癌, 半胱氨酸蛋白酶抑制剂4, 血清肿瘤标记物, 预后

Abstract: OBJECTIVE： To evaluate the value of serum cystatin 4 (CST4) levels in the clinical diagnosis and prognosis evaluation of pancreatic cancer. METHODS： From October 2020 to January 2023，71 newly diagnosed pancreatic cancer patients who were treated in the Fourth Hospital of Hebei Medical University were selected for our study，and their clinical indicators including blood routine，coagulation function，blood biochemistry，and serum tumor markers were collected. Differences in CST4 and other clinical laboratory test results between these patients and patients with benign pancreatic tumors were analyzed. Receiver operating curve (ROC) analysis were performed to evaluate the significance of CST4 in the diagnosis and clinical progression assessment of pancreatic cancer. Kaplan-Meier survival curves were constructed，and multivariate Cox regression analysis was conducted to evaluate the value of CST4 in the clinical prognosis assessment of pancreatic cancer compared with traditional tumor markers：carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). RESULTS： Compared with the benign tumors group，the proportions and median values of serum CST4，CA19-9，and CEA levels in pancreatic cancer patients were significantly increased (P<0.01). ROC analysis showed that the area under the curve (AUC) of CST4 in the diagnosis of pancreatic cancer was 0.782，and the AUC of CST4 combined with CEA and CA19-9 was significantly higher than that of single detection (AUC=0.930) (P<0.05). CST4 showed higher value in predicting the clinical progression of pancreatic cancer (AUC=0.794)，with a sensitivity of 80.90%，specificity of 70.80%，positive likelihood ratio of 2.77，and an optimal cutoff value of 84.41 U/mL. Prognostic analysis showed that the median survival times of high CST4 group and low CST4 group patients were significantly different at 6.2 months and 25.6 months (P<0.01). Elevated serum CST4 level was identified as an independent risk factor for the prognosis of pancreatic cancer (P<0.05). CONCLUSION： Our data show that serum CST4 level can be used as a clinical auxiliary diagnostic indicator for pancreatic cancer and as an independent risk factor for the prognosis of pancreatic cancer.

Key words: pancreatic cancer, cystatin 4, serum tumor markers, prognosis

中图分类号:

R733.7

郭秀娟, 贾聿明, 颜晰, 赵红峥, 郭奕阳, 张金艳. 半胱氨酸蛋白酶抑制剂4在胰腺癌临床诊断及预后评估中的价值[J]. 癌变·畸变·突变, 2024, 36(6): 463-469.

GUO Xujuan, JIA Yuming, YAN Xi, ZHAO Hongzheng, GUO Yiyang, ZHANG Jinyan. Clinical value of CST4 in auxiliary diagnosis and prognosis assessment of pancreatic cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(6): 463-469.

参考文献

[1] 徐近. 中国抗癌协会胰腺癌整合诊治指南(精简版)[J]. 中国肿瘤临床, 2023, 50(10): 487-496.
[2] 中华医学会检验分会, 卫生部临床检验中心, 中华检验医学杂志编辑委员会. 肿瘤标志物的临床应用建议[J]. 中华检验医学杂志, 2012, 35(2): 103-116.
[3] 董经茹, 白云鹤, 何京, 等. 基于生物信息学筛选与分析胰腺癌的生物标志物半胱氨酸蛋白酶抑制剂S[J]. 中国免疫学杂志, 2022, 38(24): 3030-3034.
[4] CAI J, CHEN H D, LU M, et al. Advances in the epidemiology of pancreatic cancer: trends, risk factors, screening, and prognosis[J]. Cancer Lett, 2021, 520: 1-11.
[5] ZHAO Z Y, LIU W. Pancreatic cancer: a review of risk factors, diagnosis, and treatment[J]. Technol Cancer Res Treat, 2020, 19: 1533033820962117.
[6] ZHANG W, JI L C, WANG X J, et al. Nomogram predicts risk and prognostic factors for bone metastasis of pancreatic cancer: a population-based analysis[J]. Front Endocrinol, 2021, 12: 752176.
[7] GE L, PAN B, SONG F J, et al. Comparing the diagnostic accuracy of five common tumour biomarkers and CA19-9 for pancreatic cancer: a protocol for a network meta-analysis of diagnostic test accuracy[J]. BMJ Open, 2017, 7(12): e018175.
[8] FAHRMANN J F, SCHMIDT C M, MAO X Y, et al. Lead-time trajectory of CA19-9 as an anchor marker for pancreatic cancer early detection[J]. Gastroenterology, 2021, 160(4): 1373-1383.e6.
[9] PAVAI S, YAP S F. The clinical significance of elevated levels of serum CA 19-9[J]. Med J Malaysia, 2003, 58(5): 667-672.
[10] PORUK K E, GAY D Z, BROWN K, et al. The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates[J]. Curr Mol Med, 2013, 13(3): 340-351.
[11] HOGENDORF P, SKULIMOWSKI A, DURCZY-SKI A, et al. A panel of CA19-9, Ca125, and Ca15-3 as the enhanced test for the differential diagnosis of the pancreatic lesion[J]. Dis Markers, 2017, 2017: 8629712.
[12] GU Y L, LAN C, PEI H, et al. Applicative value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis for patients with pancreatic cancer treated by concurrent chemoradiotherapy[J]. Asian Pac J Cancer Prev, 2015, 16(15): 6569-6573.
[13] ZHANG Y Q, ZHANG J J, SONG H J, et al. Overexpression of CST4 promotes gastric cancer aggressiveness by activating the ELFN2 signaling pathway[J]. Am J Cancer Res, 2017, 7(11): 2290-2304.
[14] SHI D, ZHOU Z, ZHANG S. miRNA-6715-5p inhibits cellular proliferation and invasion in colorectal cancer by directly targeting CST4[J]. J Oncol, 2021, 2021: 7615712.
[15] CHEN Y Y, LI B P, WANG J F, et al. Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer[J]. BMC Cancer, 2023, 23(1): 1122.
[16] HUANG M Y, YANG Z Y, REN J Q, et al. The diagnosis significance of serum cysteine protease inhibitors (CST4) in colorectal cancer[J]. Technol Cancer Res Treat, 2023, 22: 15330338231164232.
[17] 赵安娜, 吴爽, 张海平, 等. CST4在胃癌人群检测中的临床意义[J]. 分子诊断与治疗杂志, 2023, 15(4): 559-563.
[18] SCARÀ S, BOTTONI P, SCATENA R. CA 19-9: biochemical and clinical aspects[J]. Adv Exp Med Biol, 2015, 867: 247-260.
[19] VAN MANEN L, GROEN J V, PUTTER H, et al. Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis[J]. Biomarkers, 2020, 25(2): 186-193.
[20] 张定富, 吴秋芳, 戈长征. 肿瘤标记物CA19-9、CA242对胰腺癌转移和预后预测价值的分析[J]. 现代肿瘤医学, 2017, 25(8): 1258-1260.