循环肿瘤细胞检测在食管胃交界腺癌患者中的临床价值

马国军; 李阳; 付建华; 杨大伟

doi:10.16766/j.cnki.issn.1674-4152.003417

循环肿瘤细胞检测在食管胃交界腺癌患者中的临床价值

doi: 10.16766/j.cnki.issn.1674-4152.003417

1.
聊城市人民医院胸外科，山东聊城 252000
2.
聊城市人民医院中原生物医学研究院

基金项目:

山东省自然科学基金项目 ZR2021MH215

聊城市重点研发计划 2022YDSF37

详细信息

通讯作者:
杨大伟，E-mail：yangdawei775@163.com

中图分类号: R735.1 R735.2 R730.43
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- 被引次数: 0
出版历程
- 收稿日期: 2023-07-26
- 网络出版日期: 2024-05-27

Clinical value of count of circulating tumor cells detection in patients with adenocarcinoma of esophagogastric junction

1.
Department of thoracic Surgery, Liaocheng people ' s Hospital, Liaocheng, Shandong 252000, China

摘要

摘要: 目的研究外周血循环肿瘤细胞(CTCs)计数与食管胃交界腺癌(AEG)患者临床特征和总生存期(OS)的关系，探讨CTCs检测在AEG患者中的临床应用价值。方法回顾性分析聊城市人民医院2016年7月—2020年6月收治的154例AEG患者的临床资料，患者治疗前1周均采用阴性富集-荧光原位杂交技术行CTCs检测，分析CTCs计数与患者临床特征及OS的关系。结果在早期(Ⅰ~Ⅱ期)AEG患者中，CTCs阳性率为57.1%(32/56)，癌胚抗原(CEA)、糖类抗原(CA)19-9、CA72-4的阳性率分别为19.6%(11/56)、1.8%(1/56)、12.5%(7/56)。不同CTCs计数AEG患者脉管内瘤栓(χ²=45.262，P < 0.001)、TNM分期(χ²=14.304，P < 0.001)、淋巴结转移(χ²=5.158，P=0.023)差异均有统计学意义。Log-rank单因素分析提示，CTCs≥2(χ²=12.486，P < 0.001)以及CTCs≥3(χ²=45.344，P < 0.001)与AEG患者OS相关。Cox多因素分析显示，CTCs≥3(HR=2.459，95% CI：1.472~4.107，P=0.001)是AEG患者OS的独立危险因素。结论阴性富集-荧光原位杂交技术检测CTCs可作为早期AEG患者的辅助诊断指标，与AEG患者的病理分期以及肿瘤复发转移相关，CTCs≥3可作为AEG患者预后不良的独立危险因素，具有一定的临床应用价值。
- 食管胃交界腺癌 /
- 循环肿瘤细胞 /
- 总生存期
Abstract: Objective To investigate the relationship between the count of circulating tumor cells (CTCs) in peripheral blood and the clinical characteristics and overall survival (OS) of patients with adenocarcinoma of esophagogastric junction (AEG), and to explore the clinical application value of CTCs detection in AEG patients. Methods A total of 154 patients with AEG were eligible for enrollment in Liaocheng People ' s Hospital from July 2016 to June 2020 in the retrospective study. Negative enrichment techniques and fluorescence in situ hybridization (NE-FISH) were used to detect CTCs one week before treatment and the relationship between CTCs count and clinical characteristics of AEG patients was then investigated. Moreover, relationship between CTCs count and OS in prognosis were also explored. Results The positive rate of CTCs was 57.1% (32/56) and the positive rates of CEA, CA19-9 and CA72-4 were 19.6% (11/56), 1.8% (1/56) and 12.5% (7/56) respectively in the early AEG patients. The presence of CTCs was significantly correlated with AEG patients, CTCs were positive (≥2) in patients with AEG was significantly correlated with intravascular tumor thrombus (χ²=45.262, P < 0.001), TNM stage (χ²=14.304, P < 0.001)and lymph node metastasis (χ²=5.158, P=0.023). Log-rank univariate analysis showed that CTCs ≥ 2 (χ²=12.486, P < 0.001) and CTCs ≥ 3 (χ²=45.344, P < 0.001) were closely related to OS in AEG patients(P < 0.001). Cox multivariate analysis showed that CTCs ≥ 3 (HR=2.459, 95% CI: 1.472-4.107, P=0.001) was an independent risk factor for the prognosis of OS in AEG patients. Conclusion The detection of CTCs by negative enrichment fluorescence in situ hybridization can be used as an auxiliary diagnostic indicator for early AEG patients, which is closely related to the pathological stage of AEG patients and tumor recurrence and metastasis. CTCs ≥ 3 can be used as an independent risk factor for poor prognosis of AEG patients and have a certain clinical application value.
- Adenocarcinoma of esophagogastric junction /
- Circulating tumor cells /
- Overall survival

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图 1 阴性富集-荧光原位杂交技术检测AEG患者外周血CTCs

Figure 1. Detection of CTCs in the peripheral blood of patients with AEG using negative enrichment-fluorescence in situ hybridization technology

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图 2 CTCs≥2与CTCs < 2的AEG患者OS生存曲线

Figure 2. OS survival curves of AEG patients with CTCs≥2 and CTCs < 2

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图 3 CTCs≥3与CTCs < 3的AEG患者OS生存曲线

Figure 3. OS survival curves of AEG patients with CTCs≥3 and CTCs < 3

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表 1 不同CTCs计数AEG患者临床特征比较[例(%)]

Table 1. Comparison of clinical features in AEG patients with different CTCs counts [cases (%)]

项目	例数	CTCs计数		χ²值	P值
项目	例数	< 2	≥2	χ²值	P值
性别				2.156	0.142
男性	131	36(27.5)	95 (72.5)
女性	23	3 (13.0)	20 (87.0)
年龄(岁)				1.257	0.262
< 65	59	12 (20.3)	47 (79.7)
≥65	95	27 (28.4)	68 (71.6)
肿瘤分化程度				4.958	0.026
高分化	14	7 (50.0)	7 (50.0)
中低分化	140	32 (22.9)	108(77.1)
脉管内癌栓				45.262	< 0.001
无	54	31 (57.4)	23 (42.6)
有	100	8 (8.0)	92 (92.0)
T分期				9.082	0.003
T1+T2	36	16 (44.4)	20 (55.6)
T3+T4	118	23 (19.5)	95 (80.5)
淋巴结转移				5.158	0.023
无	35	14 (40.0)	21 (60.0)
有	119	25 (21.0)	94 (79.0)
TNM分期				14.304	< 0.001
Ⅰ~Ⅱ期	56	24 (42.9)	32 (57.1)
Ⅲ~Ⅳ期	98	15 (15.3)	83 (84.7)
CEA(ng/mL)				1.781	0.182
< 5	101	29 (28.7)	72 (71.3)
≥5	53	10 (18.9)	43 (81.1)
CA19-9(U/mL)				2.177	0.140
< 39	136	37 (27.2)	99 (72.8)
≥39	18	2 (11.1)	16 (88.9)
CA72-4(U/mL)				0.464	0.540
< 6.9	112	30 (26.8)	82 (73.2)
≥6.9	42	9 (21.4)	33 (78.6)

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表 2 不同临床特征AEG患者中位OS比较

Table 2. Comparison of median OS in AEG patients with different clinical characteristics

项目	例数	中位OS(95% CI，月)	χ²值	P值
性别			0.502	0.479
男性	131	27.00(21.11~32.89)
女性	23	29.00(16.57~41.43)
年龄(岁)			0.987	0.321
< 65	59	30.00(19.26~40.74)
≥65	95	24.00(18.66~29.34)
肿瘤分化程度			0.310	0.578
高分化	14	36.00(23.30~48.70)
中低分化	140	24.00(18.23~29.77)
CTCs			12.486	< 0.001
< 2	39	50.00(40.39~59.61)
≥2	115	20.00(15.40~24.59)
CTCs			45.344	< 0.001
< 3	67	50.00(38.97~61.03)
≥3	87	15.00(11.95~18.05)
脉管内癌栓			29.318	< 0.001
有	100	17.00(12.11~21.89)
无	54	49.00(41.80~56.20)
T分期			1.285	0.257
T1+T2	36	36.00(22.79~49.21)
T3+T4	118	21.00(16.09~25.91)
淋巴结转移			12.299	< 0.001
有	35	21.00(16.51~25.49)
无	119	52.00(45.48~58.52)
TNM分期			17.627	< 0.001
Ⅰ~Ⅱ	56	49.00(40.62~57.38)
Ⅲ~Ⅳ	98	17.00(12.15~21.85)
CEA(ng/mL)			10.837	0.001
< 5	101	33.00(27.26~38.75)
≥5	53	13.00(9.94~16.06)
CA19-9(U/mL)			27.934	< 0.001
< 39	136	30.00(25.48~34.52)
≥39	18	10.00(7.93~12.07)
CA72-4(U/mL)			14.371	< 0.001
< 6.9	112	31.00(25.88~36.12)
≥6.9	42	13.00(9.49~16.51)

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表 3 AEG患者OS影响因素的Cox多因素回归分析

Table 3. Cox multivariate regression analysis of factors influencing OS in AEG patients

变量	B	SE	Waldχ²	P值	HR值(95%CI)
性别(男性vs. 女性)	0.173	0.263	0.434	0.510	1.189(0.711~1.989)
年龄(< 65岁vs. ≥65岁)	0.108	0.192	0.315	0.575	1.114(0.764~1.623)
CTCs(< 2 vs. ≥2)	0.123	0.281	0.190	0.663	1.130(0.651~1.962)
CTCs(< 3 vs. ≥3)	0.900	0.262	11.806	0.001	2.459(1.472~4.107)
分化程度(高vs. 中低)	-0.198	0.365	0.294	0.588	0.820(0.401~1.678)
T分期(T1+T2 vs. T3+T4)	-0.513	0.322	2.535	0.111	0.599(0.318~1.126)
淋巴结转移(有vs. 无)	-0.015	0.324	0.002	0.964	0.986(0.522~1.861)
TNM分期(Ⅰ~Ⅱ vs. Ⅲ~Ⅳ)	0.511	0.386	1.758	0.185	1.668(0.783~3.552)
脉管内瘤栓(无vs. 有)	0.229	0.255	0.807	0.369	1.257(0.763~2.071)
CEA(< 5 ng/mL vs. ≥5 ng/mL)	-0.084	0.212	0.155	0.694	0.920(0.607~1.395)
CA19-9(< 39 U/mL vs. ≥39 U/mL)	0.704	0.290	5.882	0.015	2.022(1.145~3.572)
CA72-4(< 6.9 U/mL vs. ≥6.9 U/mL)	0.458	0.234	3.830	0.050	1.580(0.999~2.499)
注：变量赋值方法如下，性别(男性=0，女性=1)，年龄(< 65岁=0，≥65岁=1)，CTCs(< 2=0，≥2=1)，CTCs(< 3=0，≥3=1)，分化程度(高=0，中低=1)，T分期(T1+T2=0，T3+T4=1)，淋巴结转移(有=1，无=0)，TNM分期(Ⅰ+Ⅱ=0，Ⅲ+Ⅳ=1)，脉管内瘤栓(无=0，有=1)，CEA(< 5 ng/mL=0，≥5 ng/mL=1)，CA19-9(< 39 U/mL=0，≥39 U/mL=1)，CA72-4(< 6.9 U/mL=0，≥6.9 U/mL=1)。

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参考文献(18)

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. Ca Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	WANG H L, ZHAO X K, ZHOU F Y, et al. Characterization of e-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis[J]. World J Gastrointest Oncol, 2022, 14(1): 265-277. doi: 10.4251/wjgo.v14.i1.265
[3]	LI Y, MA G, ZHAO P, et al. Improvement of sensitive and specific detection of circulating tumor cells using negative enrichment and immunostaining-fish[J]. Clin Chim Acta, 2018, 485(1): 95-102.
[4]	MA G, YANG D, LI Y, et al. Combined measurement of circulating tumor cell counts and serum tumor marker levels enhances the screening efficiency for malignant versus benign pulmonary nodules[J]. Thorac Cancer, 2022, 13(23): 3393-3401. doi: 10.1111/1759-7714.14702
[5]	LI Y, WANG Z, FU R, et al. Clinical utility of circulating tumor cells in patients with esophageal cancer[J]. Front Oncol, 2022, 12(2): 60-68.
[6]	JELSKI W, MROCZKO B. Molecular and circulating biomarkers of gastric cancer[J]. Int J Mol Sci, 2022, 23(14): 75-88.
[7]	MA S, ZHOU M, XU Y, et al. Clinical application and detection techniques of liquid biopsy in gastric cancer[J]. Mol Cancer, 2023, 22(1): 7. doi: 10.1186/s12943-023-01715-z
[8]	XU J, LIAO K, YANG X, et al. Using single-cell sequencing technology to detect circulating tumor cells in solid tumors[J]. Mol Cancer, 2021, 20(1): 96-104. doi: 10.1186/s12943-021-01388-6
[9]	GALVIS M M, ROMERO C S, BUENO T O, et al. Toward a new era for the management of circulating tumor cells[J]. Adv Exp Med Biol, 2021, 1286(3): 125-134.
[10]	MA X, OU K, LIU X, et al. Application progress of liquid biopsy in gastric cancer[J]. Front Oncol, 2022, 12(10): 54-66.
[11]	GKOUNTELA S, CASTRO-GINER F, SZCZERBA B M, et al. Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding[J]. Cell, 2019, 176(2): 98-112.
[12]	CHENG B, TONG G, WU X, et al. Enumeration and characterization of circulating tumor cells and its application in advanced gastric cancer[J]. Onco Targets Ther, 2019, 12(6): 7887-7896.
[13]	JHI J H, KIM G H, PARK S J, et al. Circulating tumor cells and twist expression in patients with metastatic gastric cancer: a preliminary study[J]. J Clin Med, 2021, 10(19): 70-81.
[14]	YANG Y, ZHENG J, LI Y. Comparison of 4 lymph node staging systems for the prognostic prediction of esophagogastric junction adenocarcinoma with ≤ 15 retrieved lymph nodes[J]. Eur J Surg Oncol, 2022, 48(5): 1017-1024. doi: 10.1016/j.ejso.2021.11.133
[15]	ZENG C D D, JIN C C, GAO C, et al. Preoperative folate receptor-positive circulating tumor cells are associated with occult peritoneal metastasis and early recurrence in gastric cancer patients: a prospective cohort study[J]. Front Oncol, 2022, 29(12): 191-203.
[16]	赵天豪, 杨一群, 李岳彤, 等. 泛素结合酶2S在胃癌中的表达及临床意义[J]. 中华全科医学, 2023, 21(4): 555-559. doi: 10.16766/j.cnki.issn.1674-4152.002929 ZHAO T H, YANG Y Q, LI Y T, et al. Expression and clinical significance of UBE2S in gastric cancer[J]. Chinese Journal of General Practice, 2023, 21(4): 555-559. doi: 10.16766/j.cnki.issn.1674-4152.002929
[17]	SONG X H, LIU K, YANG S J, et al. Prognostic value of changes in preoperative and postoperative serum CA19-9 levels in gastric cancer[J]. Front Oncol, 2020, 10(2): 22-32.
[18]	WANG Y W, LI L L, LU M, et al. Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer[J]. Arch Med Sci, 2022, 18(5): 1297-1307.