Expression of PG Ⅰ/PG Ⅱ，NAP1L1，SERPINB5 in Serum of Gastric Cancer Patients and Cox Regression Analysis on Prognosis
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摘要:
目的 探讨胃蛋白酶原I/II（PG Ⅰ/PG Ⅱ）、核小体组装蛋白1-like-1（NAP1L1）、SERPINB5在胃癌患者血清中的表达及与预后的相关性。 方法 选取涿州市医院2019年2月至2022年2月收治的200例胃癌患者纳入胃癌组，另选取同期于涿州市医院接受治疗的100例胃良性病变患者纳入良性组，选取200例健康成人作为对照组。分别采用化学发光法和ELISA法血清PG Ⅰ/PG II、NAP1L1、SERPINB5水平；ROC曲线分析诊断价值；Kaplan-Meier法分析生存曲线；多因素Cox分析影响预后的因素。 结果 与对照组相比，良性组、胃癌组血清PG Ⅰ/PG Ⅱ水平降低，血清NAP1L1、SERPINB5水平升高，差异有统计学意义（P < 0.05），与良性组相比，胃癌组血清PG Ⅰ/PG Ⅱ水平降低，血清NAP1L1、SERPINB5水平升高，差异有统计学意义（P < 0.05）；PG Ⅰ/PG Ⅱ、NAP1L1、SERPINB5均是胃癌发生的影响因素；血清PGⅠ/PGⅡ、NAP1L1、SERPINB5单独诊断胃癌的AUC分别为0.821、0.808、0.833，三者联合诊断的AUC为0.916，三者联合诊断价值较优（Z = 3.142、3.896、3.114，P < 0.05）；胃癌患者3年随访期间，57例死亡，占比28.50%（57/200），143例生存；PG Ⅰ/PG Ⅱ高表达患者术后3年总生存率高于低表达患者，差异有统计学意义（χ2 = 7.830，P < 0.05）；NAP1L1、SERPINB5低表达患者术后3年总生存率高于高表达患者，差异有统计学意义（χ2 = 8.612、13.321，P < 0.05）；死亡组血清PG Ⅰ/PG Ⅱ水平低于生存组，血清NAP1L1、SERPINB5水平与术前淋巴结转移、TNM分期III～IV期患者占比高于生存组，差异有统计学意义（P < 0.05）；PG Ⅰ/PG Ⅱ升高是胃癌患者预后的保护因素，术前淋巴结转移、NAP1L1、SERPINB5升高是影响胃癌患者预后的危险因素（P < 0.05）。 结论 胃癌患者血清PGⅠ /PG Ⅱ水平下降，NAP1L1、SERPINB5水平升高，且NAP1L1、SERPINB5是影响胃癌患者预后的危险因素，PGⅠ /PG Ⅱ是保护因素。 -
关键词:
- 胃癌 /
- 胃蛋白酶原I/II /
- 核小体组装蛋白1-like-1 /
- SERPINB5 /
- 预后
Abstract:Objective To explore the expression of pepsinogen I/II （PG Ⅰ/PG Ⅱ）, nucleosome assembly protein 1 like protein 1 （NAP1L1）, and SERPINB5 in the serum of gastric cancer patients and their correlation with prognosis. Methods From February 2019 to February 2022, 200 gastric cancer patients admitted to Zhuozhou Hospital were served as the gastric cancer group and another 100 patients with benign gastric lesions who received the treatment at Zhuozhou Hospital during the same period were served as the benign group, with 200 healthy adults as the control group. Chemiluminescence and ELISA methods were used to detect the serum PG Ⅰ/PG Ⅱ, NAP1L1, and SERPINB5. ROC curve was used to explore the diagnostic value. Kaplan-Meier method was used to explore the survival curve. Moreover, multivariate Cox method was used to analyze the factors that affected the prognosis. Results Compared with the control group, the benign group and gastric cancer group had the lower serum PG Ⅰ/PG Ⅱ and higher serum NAP1L1 and SERPINB5, and the difference was statistically significant （P < 0.05）. Compared with the benign group, the gastric cancer group had the lower serum PG Ⅰ/PG Ⅱ and higher serum NAP1L1 and SERPINB5, and the difference was statistically significant （P < 0.05）. PG I/PG II, NAP1L1, and SERPINB5 were all influential factors in gastric carcinogenesis （P < 0.05）. The AUC values of serum PG Ⅰ/PG Ⅱ, NAP1L1, and SERPINB5 alone in the diagnosis of gastric cancer were 0.821, 0.808, and 0.833, respectively. The AUC of the combination of the three was 0.916, indicating that their combined diagnostic value was superior （Z = 3.142, 3.896, 3.114, P < 0.05）. During the 3-year follow-up period of gastric cancer patients, 57 cases died, accounting for 28.50% （57/200）, and 143 cases survived. Patients with the high expression of PG Ⅰ/PG Ⅱ had a higher 3-year overall survival rate after the surgery compared to those with low expression, and the difference was statistically significant （χ2 = 7.830, P < 0.05）; and patients with the low expression of NAP1L1 and SERPINB5 had a higher 3-year overall survival rate after the surgery compared to those with high expression, and the difference was statistically significant （χ2 = 8.612, 13.321, P < 0.05）. The serum PG Ⅰ/PG Ⅱ levels in the death group were lower than those in the survival group, and the serum NAP1L1, SERPINB5 levels were higher in patients with preoperative lymph node metastasis and TNM stage III-IV than those in the survival group, and the difference was statistically significant （P < 0.05）. Elevated level of PG Ⅰ/PG Ⅱ was a protective factor for the prognosis of gastric cancer patients, while preoperative lymph node metastasis, elevated levels of NAP1L1 and SERPINB5 were risk factors affecting the prognosis of gastric cancer patients （P < 0.05）. Conclusion Serum PG I /PG II levels are decreased and NAP1L1 and SERPINB5 levels are increased in gastric cancer patients, and NAP1L1 and SERPINB5 are risk factors affecting the prognosis of gastric cancer patients, while PG I /PG II is a protective factor. -
Key words:
- Gastric cancer /
- Pepsinogen I/II /
- Nucleosome assembly protein 1 like protein 1 /
- SERPINB5 /
- Prognosis
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图 1 血清PG Ⅰ/PG Ⅱ、NAP1L1、SERPINB5预测胃癌的ROC曲线
Figure 1. ROC curves of serum PG Ⅰ/PG Ⅱ，NAP1L1，and SERPINB5 in predicting gastric cancer
图 2 生存分析
A：血清PG Ⅰ/PG Ⅱ表达与预后的关系；B：血清NAP1L1表达与预后的关系；C：血清SERPINB5表达与预后的关系。
Figure 2. Survival analysis
表 1 三组一般资料比较[（$ \bar x \pm s$）/n（%）]
Table 1. Comparison of general information of the three groups [（$ \bar x \pm s$）/n（%）]
组别 n 性别 年龄（岁） 体质量指数（kg/m2） 男 女 对照组 200 116 84 57.16 ± 8.09 22.59 ± 2.38 良性组 200 115 85 56.24 ± 7.58 22.62 ± 2.41 胃癌组 200 121 79 56.78 ± 7.95 22.54 ± 2.29 F − 0.426 0.689 0.059 P − 0.808 0.502 0.943 
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表 2 三组血清PG Ⅰ/PG Ⅱ、NAP1L1、SERPINB5水平比较[（$ \bar x \pm s $）]
Table 2. Comparison of serum PG Ⅰ/PG Ⅱ，NAP1L1，and SERPINB5 levels among the three groups [（$\bar x \pm s $）]
组别 n PG Ⅰ/PG Ⅱ NAP1L1（ng/mL） SERPINB5（ng/mL） 对照组 200 6.15 ± 0.92 4.74 ± 0.63 3.13 ± 0.48 良性组 200 3.36 ± 0.47 10.43 ± 1.58 7.46 ± 1.12 胃癌组 200 2.90 ± 0.42 12.36 ± 1.89 8.85 ± 1.33 F − 1492.177 1456.451 1531.985 P − <0.001* <0.001* <0.001* *P < 0.05。
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表 3 影响胃癌的多因素Logistic回归分析
Table 3. Multifactorial logistic regression analysis of influence on gastric cancer
影响因素 B SE Waldχ2 OR 95%CI P PG Ⅰ/PG Ⅱ −1.044 0.361 8.365 0.352 0.173～0.714 0.004* NAP1L1 1.360 0.501 7.368 3.896 1.459～10.401 0.007* SERPINB5 1.396 0.442 9.972 4.038 1.698～9.603 0.002* 常量 3.600 1.136 10.041 − − 0.002* *P < 0.05。
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表 4 血清PG Ⅰ/PG Ⅱ、NAP1L1、SERPINB5对胃癌的诊断价值
Table 4. Diagnostic value of serum PG Ⅰ/PG Ⅱ，NAP1L1 and SERPINB5 in gastric cancer
指标 AUC P 最佳截断值 95%CI 灵敏度（%） 特异度（%） 约登指数 PG Ⅰ/PG Ⅱ 0.821 <0.001* 3.07 0.773～0.863 82.00 73.00 0.550 NAP1L1 0.808 0.002* 12.08 0.759～0.851 62.50 87.00 0.495 SERPINB5 0.833 <0.001* 7.76 0.785～ 0.873 74.50 84.00 0.585 三者联合 0.916 − − 0.879～0.945 95.50 74.00 0.695 *P < 0.05。
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表 5 血清PG Ⅰ/PG Ⅱ、NAP1L1、SERPINB5水平与胃癌患者3年预后的关系[n（%）]
Table 5. Relationship between serum PG Ⅰ/PG Ⅱ，NAP1L1，and SERPINB5 levels and 3-year prognosis of gastric cancer patients [n（%）]
组别 n PG Ⅰ/PG Ⅱ
高表达（n=98）PG Ⅰ/PG Ⅱ
低表达（n=102）NAP1L1
高表达（n=104）NAP1L1
低表达（n=96）SERPINB5
高表达（n=103）SERPINB5
低表达（n=97）生存组 143 79（80.61） 64（62.75） 65（62.50） 78（81.25） 62（60.19） 81（83.51） 死亡组 57 19（19.39） 38（37.25） 39（37.50） 18（18.75） 41（39.81） 16（16.49） χ2 − 7.830 8.612 13.321 P − 0.005* 0.003* <0.001* *P < 0.05。
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表 6 生存组与死亡组临床资料分析[（$\bar x \pm s $）/n（%）]
Table 6. Analysis of clinical data in the survival and mortality groups [（$\bar x \pm s $）/n（%）]
指标 生存组（n=143） 死亡组（n=57） t/Z/χ2 P 年龄（岁） 56.74 ± 8.05 58.21 ± 8.19 1.160 0.247 性别 0.379 0.538 男 81（56.64） 35（61.40） 女 62（43.36） 22（38.60） 体质量指数（kg/m2） 22.52 ± 2.37 22.76 ± 2.42 0.643 0.521 肿瘤最大径（cm） 1.459 0.227 <5 53（37.06） 16（28.07） ≥5 90（62.94） 41（71.93） 肿瘤部位 0.504 0.777 胃窦 72（50.35） 29（50.88） 胃体 46（32.17） 16（28.07） 胃底 25（17.48） 12（21.05） 分化程度 0.270 0.603 中高分化 66（46.15） 24（42.11） 低分化 77（53.85） 33（57.89） 术前淋巴结转移 35.205 <0.001* 有 40（27.97） 42（73.68） 无 103（72.03） 15（26.32） TNM分期 15.121 <0.001* I～II期 91（63.64） 19（33.33） III～IV期 52（36.36） 38（66.67） 胃癌家族史 0.037 0.847 有 4（2.80） 2（3.51） 无 139（97.20） 55（96.49） PG Ⅰ/PG Ⅱ 3.26 ± 0.47 2.01 ± 0.31 18.523 <0.001* NAP1L1（ng/mL） 11.36 ± 1.72 14.87 ± 2.24 11.908 <0.001* SERPINB5（ng/mL） 7.92 ± 1.19 11.18 ± 1.67 15.493 <0.001* *P < 0.05。
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表 7 危险因素变量赋值
Table 7. Assignment of risk factor variables
影响因素 赋值 预后情况 良好=0，不良=1 年龄 连续变量 性别 男=0，女=1 体质量指数 连续变量 肿瘤最大径（cm） <5 =0，≥5 =1 肿瘤部位 胃窦=0，胃体/胃底=1 分化程度 中高分化=0，低分化=1 术前淋巴结转移 无=0，有=1 TNM分期 I～II期=0，III～IV期=1， 胃癌家族史 无=0，有=1 PG Ⅰ/PG Ⅱ 连续变量 NAP1L1 连续变量 SERPINB5 连续变量
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表 8 影响胃癌患者预后的多因素Cox风险回归分析
Table 8. Multifactorial Cox risk regression analysis affecting the prognosis of gastric cancer patients
影响因素 B SE Waldχ2 HR 95%CI P 年龄 0.180 0.386 0.217 1.197 0.562～2.551 0.641 性别 0.490 0.325 2.277 1.633 0.864～3.088 0.131 体质量指数 0.400 0.338 1.401 1.492 0.769～2.894 0.237 肿瘤最大径 0.744 0.455 2.673 2.104 0.862～5.133 0.102 肿瘤部位 0.618 0.451 1.880 1.856 0.767～4.492 0.170 分化程度 0.873 0.488 3.200 2.394 0.920～6.230 0.074 术前淋巴结转移 1.068 0.447 5.714 2.911 1.212～6.991 0.017* TNM分期 0.857 0.508 2.849 2.357 0.871～6.379 0.091 胃癌家族史 0.643 0.529 1.477 1.902 0.674～5.364 0.224 PG Ⅰ/PG Ⅱ −1.152 0.405 8.091 0.316 0.143～0.699 0.004* NAP1L1 1.206 0.428 7.939 3.340 1.444～7.728 0.005* SERPINB5 1.481 0.453 10.684 4.396 1.809～10.682 0.001* *P < 0.05。
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