血清PGⅠ/PGⅡ联合肿瘤标志物对Hp阳性早期胃癌的诊断价值
Diagnostic Value of Serum Pepsinogen Ⅰ/Pepsinogen Ⅱ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer
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摘要:目的 探讨血清胃蛋白酶原Ⅰ(PGⅠ)/胃蛋白酶原Ⅱ(PGⅡ)联合肿瘤标志物对幽门螺杆菌(Hp)阳性早期胃癌的诊断价值。方法 回顾性分析2018年5月–2021年4月本院收治的109例胃癌患者(胃癌组)、115例慢性萎缩性胃炎患者(良性组)、112例低级别上皮内瘤变(低级别组)、109例高级别上皮内瘤变(高级别组)及104例体检筛查健康者(健康组)的临床资料,均行血清PGⅠ、PGⅡ、癌胚抗原(CEA)、糖类抗原199(CA199)、糖类抗原724(CA724)水平检测及Hp感染情况检查。对比各组上述指标,并比较各组Hp阳性者与Hp阴性者上述血清指标的差异。用受试者工作特征(ROC)曲线评估血清PGⅠ/PGⅡ联合肿瘤标志物对Hp阳性早期胃癌的诊断价值。结果 血清PGⅠ、PGⅠ/PGⅡ水平在健康组、良性组、低级别组、高级别组、胃癌组依次降低(P<0.05);胃癌组、高级别组、低级别组血清PGⅡ、CEA、CA199、CA724水平均高于健康组及良性组(P<0.05);胃癌组、高级别组、低级别组、良性组的Hp阳性率均高于健康组(P<0.01);健康组、良性组、低级别组、高级别组、胃癌组中的Hp阳性者的血清PGⅠ、PGⅡ、CEA、CA199、CA724水平均高于Hp阴性者(P<0.05),PGⅠ/PGⅡ均低于Hp阴性者(P<0.05)。血清PGⅠ/PGⅡ、CEA、CA199、CA724联合诊断Hp阳性早期胃癌的特异度与曲线下面积(AUC)均大于各指标单独诊断(P<0.05);胃癌组Hp阳性患者中PGⅠ/PGⅡ>2.32的占比低于Hp阴性者(P<0.05),CEA>66.99 ng/mL、CA199>110.35 U/mL、CA724>44.20 U/mL的占比高于Hp阴性者(P<0.05)。结论 联合检测PGⅠ/PGⅡ、CEA、CA199、CA724可提高对Hp阳性早期胃癌的诊断价值。Abstract:Objective To investigate the diagnostic value of serum pepsinogen (PG) Ⅰ/PGⅡ combined with tumor markers for Helicobacter pylori (Hp)-positive early-stage gastric cancer.Methods A retrospective study was conducted with the clinical data of 109 patients with gastric cancer (the gastric cancer group), 115 patients with chronic atrophic gastritis (the benign group), 112 cases of low-grade intraepithelial neoplasia (the low grade group), 109 cases of high-grade intraepithelial neoplasia (the high grade group), and 104 healthy subjects who underwent the relevant screening tests as part of their general physical examination (the healthy group). All the subjects were admitted to or received care at our hospital between May 2018 and April 2021. The levels of serum PGⅠ, PGⅡ, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), and Hp infection status were examined. The findings for these indicators were compared among the groups, and the differences in serum indicators in Hp-positive and Hp-negative patients were compared. The diagnostic value of serum PGⅠ/PGⅡ combined with tumor markers for Hp-positive early-stage gastric cancer was assessed with receiver operating characteristic (ROC) curve.Results The serum levels of PGⅠ and PGⅠ/PGⅡ decreased in successive order in the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group (P<0.05). The serum levels of PGⅡ, CEA, CA199, and CA724 in the gastric cancer group, the high grade group, and the low grade group were all higher than those in the healthy group and the benign group (P<0.05). The Hp-positive rates of the gastric cancer group, the high grade group, the low grade group and the benign group were higher than that of the healthy group (P<0.01). The levels of serum PGⅠ, PGⅡ, CEA, CA199, and CA724 of the Hp-positive subjects of the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group were higher than those of the Hp-negative subjects (P<0.05), while their PGⅠ/PGⅡ levels were always lower than those of the Hp-negative persons (P<0.05). The specificity and area under the curve (AUC) of serum PGⅠ/PGⅡ, CEA, CA199, and CA724 in the combined diagnosis of Hp-positive early-stage gastric cancer were higher than those of each indicator used alone in diagnosis (P<0.05). In the gastric cancer group, the proportion of patients with PGⅠ/PGⅡ>2.32 was lower in the Hp-positive patients than that in the Hp-negative patients (P<0.05), while the proportions of patients with CEA>66.99 ng/mL, CA199>110.35 U/mL, and CA724>44.20 U/mL were higher in the Hp-positive patients than those in the Hp-negative patients (P<0.05).Conclusion Testing PGⅠ/PGⅡ in combination with CEA, CA199, and CA724 results in better diagnostic value for Hp-positive early-stage gastric cancer.
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Keywords:
- Pepsinogen /
- Tumor markers /
- Gastric cancer /
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Helicobacter pylori
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表 1 各组一般资料比较
Table 1 Comparison of general data of each group
Group n Sex/case Age/yr. Body mass index/
(kg/m2)Clinical stage/case Type/case Smoking
history/caseDrinking
history/caseMale Female 0 Ⅰ Ⅱ Protuberant Flat Sunken Gastric cancer 109 61 48 54.08±
10.3523.46±
3.175 65 39 31 56 22 33 36 Benign 115 60 55 51.95±
9.4222.96±
3.24- - - - - - 30 32 Low grade 112 59 53 53.08±
10.4623.15±
3.21- - - - - - 32 35 High grade 109 58 51 53.69±
10.2723.26±
3.11- - - - - - 29 33 Healthy 104 56 48 52.97±
10.1622.59±
4.06- - - - - - 27 30 χ2/F 0.564 0.720 1.023 - - - - - - 1.062 0.841 P 0.379 0.579 0.395 - - - - - - 0.183 0.225 表 2 各组血清指标对比
Table 2 Comparison of serum indicators in each group
Group n PGⅠ/(μg/L) PGⅡ/(μg/L) PGⅠ/PGⅡ CEA/(ng/mL) CA199/(U/mL) CA724/(U/mL) Healthy 104 135.64±21.38 12.06±2.51 11.25±2.06 2.89±0.57 11.49±2.23 3.17±0.63 Benign 115 115.43±20.71a 13.49±2.68 8.57±1.58a 3.04±0.60 12.06±2.35 3.32±0.66 Low grade 112 103.29±20.12a, b 14.81±2.37a, b 6.97±1.24a, b 6.72.±1.39a, b 23.58±4.39a, b 7.19±1.32a, b High grade 109 91.48±20.23a, b, c 15.96±2.45a, b, c 5.73±1.16a, b, c 8.45±1.64a, b, c 27.87±5.26a, b, c 8.85±1.57a, b, c Gastric cancer 109 57.86±8.33a, b, c, d 27.52±5.37a, b, c, d 2.10±0.41a, b, c, d 69.72±11.46a, b, c, d 126.47±24.38a, b, c, d 65.08±10.57a, b, c, d F 4189.499 3976.748 4008.428 5016.006 3709.426 5316.842 P 0.000 0.000 0.000 0.000 0.000 0.000 a P<0.05, vs. healthy group; b P<0.05, vs. benign group; c P<0.05, vs. low grade group; d P<0.05, vs. high grade group. 表 3 各组Hp阳性、阴性者血清指标水平对比
Table 3 Comparison of serum indicator levels of Hp-positive and Hp-negative subjects in each group
Group Hp n PGⅠ/(μg/L) PGⅡ/(μg/L) PGⅠ/PGⅡ CEA/(ng/mL) CA199/(U/mL) CA724/(U/mL) Healthy + 26 148.57±23.56 14.59±2.36 10.18±2.02 3.85±0.54 13.06±2.15 3.98±0.63 - 78 131.33±20.49a 11.22±2.19a 11.70±2.13a 2.57±0.42a 10.97±1.92a 2.90±0.44a Benign + 90 120.61±21.03 15.36±2.11 7.85±1.41 3.48±0.61 13.57±2.24 3.85±0.52 - 25 96.78±16.35a 6.76±1.29a 14.32±2.03a 1.46±0.28a 6.62±1.16a 1.41±0.26a Low grade + 86 110.65±18.36 16.97±2.25 6.52±1.33 7.44±1.42 25.56±5.45 7.88±1.36 - 26 79.38±14.26a 7.79±1.32a 10.19±1.65a 4.34±0.83a 17.03±3.32a 4.91±0.88a High grade + 83 99.52±16.73 18.22±2.46 5.46±1.21 9.26±1.69 29.35±6.04 9.51±1.57 - 26 65.81±12.18a 8.75±1.37a 7.52±1.28a 5.86±1.17a 23.15±4.71a 6.74±1.26a Gastric cancer + 81 61.39±10.48 30.95±5.63 1.98±0.36 86.79±15.64 148.62±23.56 77.25±14.39 - 28 47.65±6.27a 17.60±3.39a 2.71±0.48a 23.73±4.16a 72.79±14.08a 34.85±5.46a a P<0.05, vs. Hp-positve subjects. 表 4 ROC曲线结果分析
Table 4 ROC curve result analysis
Predictive factor Cut-off Sensitivity Specificity AUC 95% CI PGⅠ/PGⅡ 2.32 80.25% 75.00% 0.828 0.743-0.893 CEA 66.99 ng/mL 77.78% 75.00% 0.795 0.707-0.867 CA199 110.35 U/mL 81.48% 71.43% 0.685 0.589-0.770 CA724 44.20 U/mL 79.01% 78.57% 0.759 0.667-0.836 Combination 75.31% 96.43% 0.924 0.857-0.966 表 5 各组Hp阳性、Hp阴性者应用cut-off值筛选阳性人群比较〔例数(%)〕
Table 5 Comparison of Hp-positive and Hp-negative subjects in each group, using cut-off value to screen for positive population (case [%])
Group Hp n PGⅠ/PGⅡ CEA/(ng/mL) CA199/(U/mL) CA724/(U/mL) >2.32 ≤2.32 >66.99 ≤66.99 >110.35 ≤110.35 >44.20 ≤44.20 Healthy + 26 24 (92.31) 2 (7.69) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) - 78 77 (98.72) 1 (1.28) 0 (0.00) 78 (100.00) 0 (0.00) 78 (100.00) 0 (0.00) 78 (100.00) Benign + 90 83 (92.22) 7 (7.78) 0 (0.00) 90 (100.00) 0 (0.00) 90 (100.00) 0 (0.00) 90 (100.00) - 25 25 (100.00) 0 (0.00) 0 (0.00) 25 (100.00) 0 (0.00) 25 (100.00) 0 (0.00) 25 (100.00) Low grade + 86 71 (85.54) 15 (18.07) 0 (0.00) 86 (100.00) 0 (0.00) 86 (100.00) 0 (0.00) 86 (100.00) - 26 25 (96.15) 1 (3.85) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) High grade + 83 72 (86.75) 11 (13.25) 1 (1.20) 82 (98.80) 2 (2.41) 81 (97.59) 1 (1.20) 82 (98.80) - 26 24 (92.31) 2 (7.69) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) 0 (0.00) 26 (100.00) Gastric cancer + 81 16 (19.75)a 65 (80.25)a 63 (77.78)a 18 (22.22)a 66 (81.48)a 15 (18.52)a 64 (79.01)a 17 (20.99)a - 28 21 (75.00) 7 (25.00) 7 (25.00) 21 (75.00) 8 (28.57) 20 (71.43) 6 (21.43) 22 (78.57) a P<0.05, vs. Hp-negative patients in gastric cancer group. -
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