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血清PGⅠ/PGⅡ联合肿瘤标志物对Hp阳性早期胃癌的诊断价值

王珊珊, 郭战萍, 赵翔宇

王珊珊, 郭战萍, 赵翔宇. 血清PGⅠ/PGⅡ联合肿瘤标志物对Hp阳性早期胃癌的诊断价值[J]. 四川大学学报(医学版), 2023, 54(1): 186-191. DOI: 10.12182/20230160111
引用本文: 王珊珊, 郭战萍, 赵翔宇. 血清PGⅠ/PGⅡ联合肿瘤标志物对Hp阳性早期胃癌的诊断价值[J]. 四川大学学报(医学版), 2023, 54(1): 186-191. DOI: 10.12182/20230160111
WANG Shan-shan, GUO Zhan-ping, ZHAO Xiang-yu. Diagnostic Value of Serum Pepsinogen Ⅰ/Pepsinogen Ⅱ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer[J]. Journal of Sichuan University (Medical Sciences), 2023, 54(1): 186-191. DOI: 10.12182/20230160111
Citation: WANG Shan-shan, GUO Zhan-ping, ZHAO Xiang-yu. Diagnostic Value of Serum Pepsinogen Ⅰ/Pepsinogen Ⅱ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer[J]. Journal of Sichuan University (Medical Sciences), 2023, 54(1): 186-191. DOI: 10.12182/20230160111

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

  • 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.

     

  • 胃癌是消化道常见恶性肿瘤,发病率与病死率均较高,严重危害人们身体健康。研究表明,幽门螺杆菌(Helicobacter pylori, Hp)感染是胃癌发病的重要因素,在我国胃癌高发地区,Hp感染率可达60%以上[1]。早发现、早诊断以及早治疗是临床防治胃癌的重要内容。胃蛋白酶原(pepsinogen, PG)包括PGⅠ与PGⅡ,是反映胃黏膜形态及功能的重要指标,已有研究[2]显示PGⅠ、PGⅠ/PGⅡ在胃癌早期筛查中具有一定的应用价值,且与Hp感染有一定关系。但因血清PGⅠ、PGⅡ水平亦受慢性萎缩性胃炎等疾病的影响,PGⅠ/PGⅡ检测胃癌的特异度较低,其对Hp阳性早期胃癌的诊断价值有待进一步提高。血清肿瘤标志物是临床筛查及早期辅助诊断肿瘤的常用方法之一,其中癌胚抗原(carcinoembryonic antigen, CEA)、糖类抗原199(carbohydrate antigen 199, CA199)及糖类抗原724(carbohydrate antigen 724, CA724)已被广泛应用于胃癌的早期辅助诊断中[3]。另有研究[4]显示,Hp感染与CA724表达有关。基于此,本研究特分析血清PGⅠ/PGⅡ联合CEA、CA199、CA724评估Hp阳性早期胃癌的价值,为临床提供参考。

    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。纳入标准:胃癌组均符合胃癌诊断标准[5],经活检或内镜/术后标本病理学检查证实,且癌组织局限于胃黏膜层与黏膜下层,首次诊断为胃癌,既往未接受过放化疗等相关治疗;良性组为慢性萎缩性胃炎[6]患者,经胃镜下取胃黏膜做病理检查明确诊断;低级别组、高级别组均经内镜下胃黏膜组织病理检查证实;健康组为体检健康人群,无胃、十二指肠相关病史;均行PGⅠ、PGⅡ、CEA、CA199、CA724水平及Hp检测,且临床资料保留完整。排除标准:伴有其他部位恶性肿瘤;有胃部手术史;近期服用过质子泵抑制剂、胶体铋剂、抗生素及H2受体拮抗剂等;心肝肾功能异常;上消化道急性出血。

    各组在性别、年龄、体质量指数(BMI)、吸烟史、饮酒史方面比较无差异(P>0.05),见表1。本研究符合《世界医学协会赫尔辛基宣言》的相关要求,并经新乡市中心医院伦理委员会审查批准(2022-142),所有纳入本研究患者均知情同意。

    表  1  各组一般资料比较
    Table  1.  Comparison of general data of each group
    GroupnSex/caseAge/yr.Body mass index/
    (kg/m2)
    Clinical stage/caseType/caseSmoking
    history/case
    Drinking
    history/case
    MaleFemale0ProtuberantFlatSunken
    Gastric cancer 109 61 48 54.08±
    10.35
    23.46±
    3.17
    5 65 39 31 56 22 33 36
    Benign 115 60 55 51.95±
    9.42
    22.96±
    3.24
    30 32
    Low grade 112 59 53 53.08±
    10.46
    23.15±
    3.21
    32 35
    High grade 109 58 51 53.69±
    10.27
    23.26±
    3.11
    29 33
    Healthy 104 56 48 52.97±
    10.16
    22.59±
    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
    下载: 导出CSV 
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    抽取研究对象空腹静脉血4 mL,离心并分离血清。血清PGⅠ、PGⅡ水平采取酶联免疫吸附实验检测,计算PGⅠ/PGⅡ;血清CEA、CA199、CA724水平采取电化学发光法检测,相关试剂盒均购自上海江莱生物科技有限公司。正常值范围:67 μg/L<PGⅠ<200 μg/L,PGⅡ<15 μg/L,CEA<5 ng/mL,CA199<37 U/mL,CA724<6.9 U/mL。

    采用13C尿素呼气试验法,要求研究对象禁食6 h以上,检查时让其先吹气1次,然后口服1粒尿素13C胶囊,于静坐20 min、30 min后各吹气1次(嘱用力适度),呼气完毕后立即旋紧试管盖并送检,测定结果超基准值DOB>4.4判定为Hp阳性,试剂盒购自北京勃然制药有限公司。此外,对受试者进行粪便Hp抗原、血清Hp抗体检测,另对胃癌组、良性组患者的胃黏膜组织进行病理检查,进一步明确是否为Hp感染。

    多样本计量资料采用单因素方差分析与SNK-q检验;计数资料采用χ2检验;绘制受试者工作特征(ROC)曲线,确定最佳截断点(cut-off值)、灵敏度及特异度,并计算曲线下面积(AUC)与95%可信区间(95%CI),分析血清PGⅠ/PGⅡ联合CEA、CA199、CA724对Hp阳性早期胃癌的诊断价值。P<0.05为差异有统计学意义。

    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),低级别组、高级别组和胃癌组依次增加(P<0.05)。见表2

    表  2  各组血清指标对比
    Table  2.  Comparison of serum indicators in each group
    GroupnPGⅠ/(μg/L)PGⅡ/(μg/L)PGⅠ/PGⅡCEA/(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.
    下载: 导出CSV 
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    胃癌组、高级别组、低级别组、良性组和健康组的Hp阳性率分别为74.31%(81/109)、76.15%(83/109)、76.79%(86/115)、78.26%(90/115)和25.00%(26/104)。胃癌组、高级别组、低级别组和良性组均高于健康组(P<0.01)。

    五组Hp阳性者的血清PGⅠ、PGⅡ、CEA、CA199、CA724水平均高于Hp阴性者(P<0.05),血清PGⅠ/PGⅡ均低于Hp阴性者(P<0.05)。见表3

    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
    GroupHpnPGⅠ/(μg/L)PGⅡ/(μg/L)PGⅠ/PGⅡCEA/(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.
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    根据ROC曲线,血清PGⅠ/PGⅡ、CEA、CA199、CA724联合诊断Hp阳性早期胃癌的特异度与AUC均大于各项单项诊断(P<0.05)。见图1表4

    图  1  血清PGⅠ/PGⅡ联合肿瘤标志物诊断Hp阳性早期胃癌的ROC曲线图
    Figure  1.  ROC curve of serum PG Ⅰ/PG Ⅱ combined with tumor markers in the diagnosis of Hp-positive early-stage gastric cancer
    表  4  ROC曲线结果分析
    Table  4.  ROC curve result analysis
    Predictive factorCut-offSensitivitySpecificityAUC95% CI
    PGⅠ/PGⅡ2.3280.25%75.00%0.8280.743-0.893
    CEA66.99 ng/mL77.78%75.00%0.7950.707-0.867
    CA199110.35 U/mL81.48%71.43%0.6850.589-0.770
    CA72444.20 U/mL79.01%78.57%0.7590.667-0.836
    Combination75.31%96.43%0.9240.857-0.966
    下载: 导出CSV 
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    根据上述cut-off值,胃癌组Hp阳性者中PGⅠ/PGⅡ>2.32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占比高于Hp阴性者(P<0.05)。见表5

    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 [%])
    GroupHpnPGⅠ/PGⅡCEA/(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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    胃癌是胃黏膜上皮恶性病变,其发生多与饮食生活、Hp感染等因素有关[7]。早期诊断及治疗是降低胃癌病死率的重要举措,寻求准确的检测方法以提高胃癌早期诊断率极为重要。研究[8]报道,PGⅠ、PGⅡ、PGⅠ/PGⅡ可为胃癌的早期诊断提供可靠依据,但特异度不高,且PGⅠ/PGⅡ在胃癌的筛选上较PGⅠ、PGⅡ更为敏感。有研究[9]指出,血清PGⅠ、PGⅡ、PGⅠ/PGⅡ诊断胃癌的ROC曲线AUC别为0.8317、0.6813、0.9432,表明血清PGⅠ/PGⅡ对胃癌的诊断效能更佳。另因肿瘤标志物具有检测方便快捷、安全等优点,已在胃癌的早期诊断中得以广泛应用。因此,本研究对血清PGⅠ/PGⅡ联合肿瘤标志物在Hp阳性早期胃癌的诊断价值展开探讨与分析。

    本研究中,胃癌组血清PGⅠ、PGⅠ/PGⅡ最低,血清PGⅡ、CEA、CA199、CA724最高。PGⅠ主要由胃底腺主细胞以及颈黏液细胞分泌,当胃黏膜萎缩病变时,主细胞及颈黏液细胞数量减少,则PGⅠ分泌量降低,但因PGⅡ亦可由胃窦、十二指肠近端和十二指肠腺分泌,则其水平变化与胃黏膜萎缩并不一致,因此,慢性萎缩性胃炎患者血清PGⅠ、PGⅠ/PGⅡ降低,而PGⅡ变化不明显[10]。胃黏膜恶性病变后,则胃底主细胞、颈黏液细胞分泌PGⅠ的能力降低,加上癌细胞对胃黏膜结构的改变,促使PGⅠ水平持续下降,但因PGⅡ主要由成熟腺细胞产生,肠上皮化生腺体能够刺激PGⅡ分泌增多,造成PGⅠ/PGⅡ降低[11]。有研究[12]表明,胃癌患者血清PGⅠ/PGⅡ低于健康者及胃癌前疾病者(如慢性萎缩性胃炎、胃溃疡等),本研究与此相符。CEA存在于多种上皮性肿瘤中,与胃癌的发生发展密切相关[13]。CA199亦叫作胃肠癌相关抗原,在消化道恶性肿瘤中明显升高[14]。CA724可见于各种胃肠道肿瘤中,是临床胃癌诊断的首选肿瘤标志物。研究[15]表明,胃癌组血清CEA、CA199水平较胃部良性疾病组、健康对照组明显升高,本研究结果与之相符。但有研究[16]报道,健康对照组、萎缩性胃炎组、上皮内瘤变组与胃癌组间的血清PGⅠ水平无差异,上皮内瘤变组、健康对照组、萎缩性胃炎组间的PGⅡ水平无差异,本研究结果与此不符,可能与纳入研究对象年龄、病程等个体间的差异有关。

    另本研究中,胃癌组、高级别组、低级别组、良性组的Hp阳性率均较健康组高,且各组Hp阳性者的血清PGⅠ、PGⅡ、CEA、CA199、CA724水平均较Hp阴性者高,而血清PGⅠ/PGⅡ较Hp阴性者低,表明胃癌、胃上皮内瘤变、慢性萎缩性胃炎的发生均与Hp感染有关,且血清PGⅠ、PGⅡ、PGⅠ/PGⅡ、CEA、CA199、CA724水平均与Hp感染具有一定的关系。Hp感染是慢性萎缩性胃炎及胃癌前病变、胃癌发病的高危因素已得到公认。Hp感染可产生脂多糖、尿素酶,刺激主细胞分泌PG,且Hp感染后能够刺激胃酸及胃泌素分泌增多,促使合成PG增加,尤其是PGⅡ增多,另Hp感染可减少生长激素分泌,从而减弱其对PG的反馈性抑制,进而增加PG水平[17]。有研究[18]表明,Hp感染的慢性萎缩性胃炎、非萎缩性胃炎、消化性溃疡及胃癌患者血清PGⅡ水平均显著升高,而血清PGⅠ/PGⅡ比率降低,本研究结果与此一致。另Hp感染后可对胃黏膜上皮产生一系列炎性刺激,导致胃上皮细胞过度增殖,继而发生瘤变甚或癌变,则血清CEA、CA199及CA724水平升高[19]

    本研究结果发现,血清PGⅠ/PGⅡ联合肿瘤标志物诊断Hp阳性早期胃癌的特异度与AUC均大于各指标单项诊断。因CEA、CA199、CA724在多种肿瘤中呈现高表达,而PGⅠ/PGⅡ在胃炎、胃溃疡等疾病中亦有所改变,故采用单项肿瘤标志物或PGⅠ/PGⅡ对Hp阳性早期胃癌进行诊断,价值受限。联合检测PGⅠ/PGⅡ与CEA、CA199、CA724,虽灵敏度稍微降低,但特异度明显提升,有利于对Hp阳性早期胃癌进行正确评估。进一步利用ROC曲线获得的cut-off值筛选阳性人群,发现胃癌组Hp阳性者中PGⅠ/PGⅡ>2.32占比低于Hp阴性者,而CEA>66.99 ng/mL、CA199>110.35 U/mL、CA724>44.20 U/mL占比高于Hp阴性者,表明PGⅠ/PGⅡ、CEA、CA199、CA724可作为筛选Hp阳性早期胃癌的重要参考指标。

    本研究不足之处:本研究样本量相对较小,受样本量的限制,未分析在不同Hp状态下,联合诊断模型对各亚组的诊断价值,未能筛选出最适合该诊断模型的早癌人群,研究结果存在一定的局限性。

    综上,联合检测PGⅠ/PGⅡ与CEA、CA199、CA724可提高对Hp阳性早期胃癌的诊断价值,有利于临床早发现及早治疗。后续需扩充样本量进一步深入探索,以筛选出联合检测最适合的早癌人群。

    *    *    *

    利益冲突 所有作者均声明不存在利益冲突

  • 图  1   血清PGⅠ/PGⅡ联合肿瘤标志物诊断Hp阳性早期胃癌的ROC曲线图

    Figure  1.   ROC curve of serum PG Ⅰ/PG Ⅱ combined with tumor markers in the diagnosis of Hp-positive early-stage gastric cancer

    表  1   各组一般资料比较

    Table  1   Comparison of general data of each group

    GroupnSex/caseAge/yr.Body mass index/
    (kg/m2)
    Clinical stage/caseType/caseSmoking
    history/case
    Drinking
    history/case
    MaleFemale0ProtuberantFlatSunken
    Gastric cancer 109 61 48 54.08±
    10.35
    23.46±
    3.17
    5 65 39 31 56 22 33 36
    Benign 115 60 55 51.95±
    9.42
    22.96±
    3.24
    30 32
    Low grade 112 59 53 53.08±
    10.46
    23.15±
    3.21
    32 35
    High grade 109 58 51 53.69±
    10.27
    23.26±
    3.11
    29 33
    Healthy 104 56 48 52.97±
    10.16
    22.59±
    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
    下载: 导出CSV

    表  2   各组血清指标对比

    Table  2   Comparison of serum indicators in each group

    GroupnPGⅠ/(μg/L)PGⅡ/(μg/L)PGⅠ/PGⅡCEA/(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.
    下载: 导出CSV

    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

    GroupHpnPGⅠ/(μg/L)PGⅡ/(μg/L)PGⅠ/PGⅡCEA/(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.
    下载: 导出CSV

    表  4   ROC曲线结果分析

    Table  4   ROC curve result analysis

    Predictive factorCut-offSensitivitySpecificityAUC95% CI
    PGⅠ/PGⅡ2.3280.25%75.00%0.8280.743-0.893
    CEA66.99 ng/mL77.78%75.00%0.7950.707-0.867
    CA199110.35 U/mL81.48%71.43%0.6850.589-0.770
    CA72444.20 U/mL79.01%78.57%0.7590.667-0.836
    Combination75.31%96.43%0.9240.857-0.966
    下载: 导出CSV

    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 [%])

    GroupHpnPGⅠ/PGⅡCEA/(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.
    下载: 导出CSV
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出版历程
  • 收稿日期:  2022-10-09
  • 修回日期:  2023-01-05
  • 网络出版日期:  2023-01-16
  • 发布日期:  2023-01-19

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