CD13在胃癌中的表达与临床病理参数的关系及其对远期预后的预测价值

张朝阳; 杨子; 李洪涛; 张文静; 赵萌; 王娟; 左芦根; 张小凤

doi:10.16766/j.cnki.issn.1674-4152.003280

CD13在胃癌中的表达与临床病理参数的关系及其对远期预后的预测价值

doi: 10.16766/j.cnki.issn.1674-4152.003280

张朝阳¹,
杨子²,
李洪涛³,
张文静⁴,
赵萌²,
王娟⁵,
左芦根²,
张小凤^6, ,

1.
蚌埠医学院第一附属医院临床试验研究中心，安徽蚌埠 233004
2.
蚌埠医学院第一附属医院胃肠外科
3.
蚌埠医学院第一附属医院肿瘤外科
4.
蚌埠医学院第一附属医院检验科
5.
蚌埠医学院第一附属医院肿瘤内科
6.
蚌埠医学院第一附属医院中心实验室

基金项目:

国家自然科学基金项目 81700476

蚌埠医学院省级重点科研平台开放课题基金项目 KFDX202202

详细信息

通讯作者:
张小凤，E-mail：byfyzxf@163.com

中图分类号: R735.2 R730.43
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- 被引次数: 0
出版历程
- 收稿日期: 2023-06-28
- 网络出版日期: 2024-01-29

The relationship between CD13 expression and clinicopathological parameters in gastric cancer and its predictive value for long term prognosis

1.
Clinical Trials Center, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的分析丙氨酰(膜)氨肽酶(CD13)在胃癌组织中的表达情况及与临床病理参数间的关系，并评估其对患者远期预后的预判价值。方法纳入2015年1月—2018年1月于蚌埠医学院第一附属医院接受胃癌根治术的患者117例，利用免疫组化法分析CD13在胃癌组织中的表达情况，并评估其与临床病理参数间的关系及对患者术后5年生存率的预测价值。结果胃癌组织中CD13表达量显著高于癌旁组织(P＜0.001)。以CD13相对表达量中位数(4.25)为界，将患者分为CD13高表达组(59例)和低表达组(58例)。CD13高表达组CEA≥5 μg/L、存在脉管浸润、T分期3~4期、N分期2~3期及病理分级3~4级的患者比例显著高于低表达组(均P＜0.05)；KM生存曲线分析显示，CD13高表达组术后5年生存率显著低于低表达组(P＜0.001)；KM分析及Cox多因素分析显示，CD13高表达(HR=2.125，95% CI：1.256~3.595)是胃癌患者术后5年生存率的独立危险因素。ROC曲线分析显示，以CD13相对表达量4.22为截点值，预测胃癌患者术后5年死亡的灵敏度为75.71%，特异度为93.62%，准确度为0.881(P＜0.001)。结论 CD13在胃癌组织中高表达与临床病理参数有关，是患者术后5年生存率的独立危险因素，并对预后评估有一定的预测价值。
- 胃癌 /
- CD13 /
- 临床病理参数 /
- 危险因素分析 /
- 生存分析
Abstract: Objective To analyze the expression of alanyl (membrane) aminopeptidase (CD13) in gastric cancer tissues and its relationship with clinicopathological parameters, and to evaluate its value in predicting the long-term prognosis of patients with gastric cancer. Methods A total of 117 patients who underwent radical gastrectomy in the First Affiliated Hospital of Bengbu Medical College from January 2015 to January 2018 were included. Immunohistochemistry was used to analyze the expression of CD13 in gastric cancer tissues and evaluate the relationship between CD13 and clinicopathological parameters, as well as the predictive value of CD13 on the 5-year postoperative survival rate of patients. Results The expression of CD13 in gastric cancer tissues was significantly higher than that in adjacent tissues (P < 0.001). Patients were divided into a high CD13 expression group (n=59) and a low CD13 expression group (n=58) based on the median relative expression of CD13 (4.25). The proportion of patients with CEA≥5 μg/L, vascular infiltration, T stages 3-4, N stages 2-3, and pathological grade 3-4 in the CD13 high expression group was significantly higher than that in the low expression group (all P < 0.05). KM survival curve analysis showed that the 5-year survival rate of patients with high CD13 expression was significantly lower than that of patients with low CD13 expression (P < 0.001). KM analysis and Cox multivariate analysis showed that high expression of CD13 (HR=2.125, 95% CI: 1.256-3.595) was an independent risk factor for the 5-year survival rate of gastric cancer patients after surgery. ROC curve analysis showed that with the relative expression level of CD13 4.22 as the cut-off value, the sensitivity, specificity and accuracy of predicting death 5 years after surgery in gastric cancer patients were 75.71%, 93.62% and 0.881 (P < 0.001). Conclusion CD13 is highly expressed in gastric cancer tissues and is closely related to clinicopathological parameters. It is an independent risk factor for the 5-year postoperative survival rate of gastric cancer patients and has certain predictive value for prognosis assessment.
- Gastric cancer /
- CD13 /
- Clinical histopathology /
- Risk factor analysis /
- Survival analysis

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图 1 CD13在胃癌组织及癌旁组织中的表达和定位(免疫组化法，×1 000)

注：A示CD13在胃癌组织中的表达情况；B示CD13在癌旁组织中的表达情况。

Figure 1. Immunohistochemical staining (SP, × 1000) for detecting the expression and localization of CD13 in gastric cancer and adjacent tissues(SP, ×1 000)

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图 2 胃癌组织中CD13表达量对患者术后5年生存率的影响

Figure 2. Effect of CD13 expression on the 5-year survival rate after surgery in gastric cancer

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图 3 CD13表达量对胃癌患者根治术后5年生存率的预测价值

Figure 3. Predictive value of CD13 expression in determining the 5-year survival rate after radical surgery in patients with gastric cancer

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表 1 胃癌组织中CD13相对表达量与患者临床病理参数间的关系[例(%)]

Table 1. Relationship between the relative expression of CD13 in gastric cancer tissues and clinicopathological parameters of patients[cases(%)]

项目	例数	CD13		χ²值	P值
项目	例数	高表达组(n=59)	低表达组(n=58)	χ²值	P值
性别				1.038	0.308
男性	70	38(54.3)	32(45.7)
女性	47	21(44.7)	26(55.3)
年龄(岁)				1.216	0.270
＜60	40	23(57.5)	17(42.5)
≥60	77	36(46.8)	41(53.2)
CEA(μg/L)				3.879	0.049
＜5	66	28(42.4)	38(57.6)
≥5	51	31(60.8)	20(39.2)
CA19-9(kU/L)				0.255	0.614
＜37	74	36(48.6)	38(51.4)
≥37	43	23(53.5)	20(46.5)
脉管浸润				3.986	0.046
有	75	43(57.3)	32(42.7)
无	42	16(38.1)	26(61.9)
病理类型				0.587	0.444
腺癌	96	50(52.1)	46(47.9)
其他	21	9(42.9)	12(57.1)
病理分级				4.155	0.042
G1~G2	38	14(36.8)	24(63.2)
G3~G4	79	45(57.0)	34(43.0)
N分期				4.514	0.034
0~1期	55	22(40.0)	33(60.0)
2~3期	62	37(59.7)	25(40.3)
T分期				4.922	0.027
0~1期	73	31(42.5)	42(57.5)
2~3期	44	28(63.6)	16(36.4)

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表 2 影响胃癌患者术后5年生存率因素分析

Table 2. Analysis of factors influencing the 5-year survival rate of postoperative gastric cancer patients

项目	KM分析		多因素分析
项目	log-rank χ²	P值	B	SE	HR值	P值	Wald χ²	95% CI
性别(女性vs.男性)	0.336	0.562
年龄(≥60岁vs.＜60岁)	0.155	0.694
CD13表达(高表达vs.低表达)	14.479	< 0.001	0.754	0.268	2.125	0.005	7.892	1.256~3.595
CEA水平(≥5 μg/L vs.＜5 μg/L)	13.304	< 0.001	0.873	0.272	2.309	0.002	9.475	1.355~3.933
CA19-9(≥37 kU/L vs.＜37 kU/L)	5.454	0.020	0.391	0.258	1.478	0.129	2.300	0.892~2.450
脉管浸润(有vs.无)	9.905	0.002	0.727	0.290	2.069	0.012	6.281	1.172~3.655
病理类型(腺癌vs.其他)	0.412	0.521
病理分级(G3~G4 vs. G1~G2)	2.040	0.153
T分期(T3~T4 vs. T1~T2)	19.238	< 0.001	1.106	0.268	23.023	< 0.001	17.081	1.789~5.109
N分期(N2~N3 vs. N0~N1)	19.313	< 0.001	0.631	0.277	1.879	0.023	5.183	1.092~3.235

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参考文献(20)

[1]	THRIFT A P, EL-SERAG H B. Burden of gastric cancer[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542. doi: 10.1016/j.cgh.2019.07.045
[2]	SMYTH E C, NILSSON M, GRABSCH H I, et al. Gastric cancer[J]. Lancet, 2020, 396(10251): 635-648. doi: 10.1016/S0140-6736(20)31288-5
[3]	SHAH D, BENTREM D. Environmental and genetic risk factors for gastric cancer[J]. J Surg Oncol, 2022, 125(7): 1096-1103. doi: 10.1002/jso.26869
[4]	PEREZ C, BOTTA C, ZABALETA A, et al. Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma[J]. Blood, 2020, 136(2): 199-209. doi: 10.1182/blood.2019004537
[5]	HE X, FENG Z, MA J, et al. Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia[J]. Blood, 2020, 135(10): 713-723. doi: 10.1182/blood.2019002779
[6]	ZHU H H, QIN Y Z, ZHANG Z L, et al. A global study for acute myeloid leukemia with RARG rearrangement[J]. Blood Adv, 2023, 7(13): 2972-2982. doi: 10.1182/bloodadvances.2022008364
[7]	李丹丹, 夏海龙, 孙小梅, 等. CD33和CD13表达与多发性骨髓瘤患者预后的关系[J]. 中国实验血液学杂志, 2022, 30(1): 146-151. LI D D, XIA H L, SUN X M, et al. The relationship between the expressions of CD33 and CD13 and the prognosis of patients with multiple myeloma[J]. Journal of Experimental Hematology, 2022, 30(1): 146-151.
[8]	GUO Q, LI X, CUI M N, et al. CD13: A key player in multidrug resistance in cancer chemotherapy[J]. Oncol Res, 2020, 28(5): 533-540. doi: 10.3727/096504020X15919605976853
[9]	LU C, AMIN M A, FOX D A. CD13/Aminopeptidase N is a potential therapeutic target for inflammatory disorders[J]. J Immunol, 2020, 204(1): 3-11. doi: 10.4049/jimmunol.1900868
[10]	NI J, WANG X, SHANG Y, et al. CD13 inhibition augments DR4-induced tumor cell death in a p-ERK1/2-independent manner[J]. Cancer Biol Med, 2021, 18(2): 569-586. doi: 10.20892/j.issn.2095-3941.2020.0196
[11]	DECOURTYE-ESPIARD L, GUILFORD P. Hereditary diffuse gastric cancer[J]. Gastroenterology, 2023, 164(5): 719-735. doi: 10.1053/j.gastro.2023.01.038
[12]	STRONG V E. Progress in gastric cancer[J]. Updates Surg, 2018, 70(2): 157-159. doi: 10.1007/s13304-018-0543-3
[13]	XIA X, ZHANG Z, ZHU C, et al. Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications[J]. Nat Commun, 2022, 13(1): 1017. doi: 10.1038/s41467-022-28492-5
[14]	ZHOU C M, WANG Y, YANG J J, et al. Predicting postoperative gastric cancer prognosis based on inflammatory factors and machine learning technology[J]. BMC Med Inform Decis Mak, 2023, 23(1): 53. doi: 10.1186/s12911-023-02150-2
[15]	何旭旭, 赵萌, 杨一群, 等. UGT8在胃癌组织中的表达及对胃癌细胞转移的调控作用[J]. 中华全科医学, 2023, 21(4): 544-548. doi: 10.16766/j.cnki.issn.1674-4152.002927 HE X X, ZHAO M, YANG Y Q, et al. UGT8 expression in gastric cancer tissues and its regulatory effect on gastric cancer metastasis[J]. Chinese Journal of General Practice, 2023, 21(4): 544-548. doi: 10.16766/j.cnki.issn.1674-4152.002927
[16]	SUN L, ZHANG L, CHEN J, et al. Activation of tyrosine metabolism in CD13⁺ cancer stem cells drives relapse in hepatocellular carcinoma[J]. Cancer Res Treat, 2020, 52(2): 604-621. doi: 10.4143/crt.2019.444
[17]	THRIFT A P, WENKER T N, EL-SERAG H B. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention[J]. Nat Rev Clin Oncol, 2023, 20(5): 338-349. doi: 10.1038/s41571-023-00747-0
[18]	LIAO H, LAI H, CHEN J, et al. Prognostic value of cross-lineage expression of the myeloid-associated antigens CD13 and CD33 in adult B-lymphoblastic leukemia: a large real-world study of 1005 patients[J]. Cancer Med, 2023, 12(8): 9615-9626. doi: 10.1002/cam4.5739
[19]	ROY-CHOWDHURI S. Molecular pathology of lung cancer[J]. Surg Pathol Clin, 2021, 14(3): 369-377. doi: 10.1016/j.path.2021.05.002
[20]	HA Y J, SHIN Y J, TAK K H, et al. Reduced expression of alanyl aminopeptidase is a robust biomarker of non-familial adenomatous polyposis and non-hereditary nonpolyposis colorectal cancer syndrome early-onset colorectal cancer[J]. Cancer Med, 2023, 12(8): 10091-10104. doi: 10.1002/cam4.5675