血清双调蛋白、间皮素对乳腺癌辅助诊断的价值

doi:10.3969/j.issn.1673-8640.2024.01.005

摘要/Abstract

摘要：

目的探讨血清双调蛋白（AREG）和间皮素（MSLN）水平在乳腺癌辅助诊断中的价值。方法选取2018年12月—2019年5月就诊于复旦大学附属肿瘤医院的女性乳腺癌患者54例（乳腺癌组）、乳腺良性病变患者38例（良性病变组）和表观健康者35名（健康对照组）。采用酶联免疫吸附试验检测血清AREG和MSLN水平。分析乳腺癌患者血清AREG和MSLN水平与临床病理特征的关系。采用受试者工作特征（ROC）曲线评估AREG、MSLN单独和联合癌胚抗原（CEA）、糖类抗原（CA）15-3检测辅助诊断乳腺癌的效能。结果与健康对照组比较，乳腺癌组血清AREG、MSLN水平均显著升高（P<0.05）。AREG、MSLN检测诊断乳腺癌的曲线下面积（AUC）分别为0.582、0.637，而血清AREG、MSLN联合CEA、CA15-3检测的AUC为0.757。乳腺癌组血清AREG、MSLN水平与病理类型和淋巴转移有关（P<0.05）。结论血清AREG、MSLN联合CEA和CA15-3检测可在乳腺癌辅助诊断中具有一定作用。

关键词: 双调蛋白, 间皮素, 乳腺癌

Abstract:

Objective To investigate the roles of serum amphiregulin（AREG） and mesothelin（MSLN） levels in the auxiliary diagnosis of breast cancer. Methods A total of 54 female patients with breast cancer（breast cancer group），38 patients with benign breast lesions（benign lesion group） and 35 apparently healthy subjects（healthy control group） were enrolled from the Cancer Hospital of Fudan University from December 2018 to May 2019. Serum AREG and MSLN levels were determined by enzyme-linked immunosorbent assay. The relationship between serum AREG and MSLN levels and clinicopathological characteristics of breast cancer patients was analyzed. The efficacy of AREG and MSLN alone and in combination with carcinoembryonic antigen（CEA） and carbohydrate antigen（CA）15-3 in the auxiliary diagnosis of breast cancer was evaluated by receiver operating characteristic（ROC） curve. Results Compared with healthy control group，serum AREG and MSLN levels in breast cancer group were increased（P<0.05）. The areas under curves（AUC） of AREG and MSLN in the diagnosis of breast cancer were 0.582 and 0.637，respectively，while the AUC of serum AREG and MSLN combined with CEA and CA15-3 was 0.757. Serum AREG and MSLN levels in breast cancer group were related with pathological types and lymphatic metastasis（P<0.05）. Conclusions Serum AREG，MSLN combined with CEA and CA15-3 can play a role in the auxiliary diagnosis of breast cancer.

Key words: Amphiregulin, Mesothelin, Breast cancer

中图分类号:

R446.1

刘泊含, 刘鷖雯, 何怡青, 卢仁泉, 杜艳, 张国良, 郭倩, 高锋, 杨翠霞. 血清双调蛋白、间皮素对乳腺癌辅助诊断的价值[J]. 检验医学, 2024, 39(1): 26-30.

LIU Bohan, LIU Yiwen, HE Yiqing, LU Renquan, DU Yan, ZHANG Guoliang, GUO Qian, GAO Feng, YANG Cuixia. Serum amphiregulin and mesothelin in auxiliary diagnosis of breast cancer[J]. Laboratory Medicine, 2024, 39(1): 26-30.

图/表 6

参考文献 19

[1]	BURSTEIN H J, CURIGLIANO G, THÜRLIMANN B, et al. Customizing local and systemic therapies for women with early breast cancer:the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021[J]. Ann Oncol, 2021, 32(10):1216-1235. DOI URL
[2]	JIA L, LI G, MA N, et al. Soluble POSTN is a novel biomarker complementing CA153 and CEA for breast cancer diagnosis and metastasis prediction[J]. BMC Cancer, 2022, 22(1):760. DOI PMID
[3]	SINGH S S, CHAUHAN S B, KUMAR A, et al. Amphiregulin in cellular physiology,health,and disease:potential use as a biomarker and therapeutic target[J]. J Cell Physiol, 2022, 237(2):1143-1156. DOI URL
[4]	NAGATHIHALLI N S, CASTELLANOS J A, LAMICHHANE P, et al. Inverse correlation of STAT3 and MEK signaling mediates resistance to RAS pathway inhibition in pancreatic cancer[J]. Cancer Res, 2018, 78(21):6235-6246. DOI PMID
[5]	XIANG G, LIU F, LIU J, et al. Prognostic role of amphiregulin and the correlation with androgen receptor in invasive breast cancer[J]. Pathol Res Pract, 2019, 215(6):152414. DOI URL
[6]	BOLITHO C, MOSCOVA M, BAXTER R C, et al. Amphiregulin increases migration and proliferation of epithelial ovarian cancer cells by inducing its own expression via PI3-kinase signaling[J]. Mol Cell Endocrinol, 2021, 533:111338. DOI URL
[7]	WANG Y, TZENG Y T, CHANG G, et al. Amphiregulin retains ERα expression in acquired aromatase inhibitor resistant breast cancer cells[J]. Endocr Relat Cancer, 2020, 27(12):671-683. DOI URL
[8]	WANG S F, CHANG Y L, TZENG Y D, et al. Mitochondrial stress adaptation promotes resistance to aromatase inhibitor in human breast cancer cells via ROS/calcium up-regulated amphiregulin-estrogen receptor loop signaling[J]. Cancer Lett, 2021, 523:82-99. DOI URL
[9]	XU Q, LONG Q, ZHU D, et al. Targeting amphiregulin(AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand(PD-L1)-mediated immunosuppression[J]. Aging Cell, 2019, 18(6):e13027. DOI URL
[10]	SCHMUCKER H, BLANDING W M, MOOK J M, et al. Amphiregulin regulates proliferation and migration of HER2-positive breast cancer cells[J]. Cell Oncol(Dordr), 2018, 41(2):159-168.
[11]	CHANG K, PASTAN I. Molecular cloning of mesothelin,a differentiation antigen present on mesothelium,mesotheliomas,and ovarian cancers[J]. Proc Natl Acad Sci U S A, 1996, 93(1):136-140. DOI URL
[12]	ATAY S. Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues[J]. PeerJ, 2020, 8:e10141. DOI URL
[13]	汪莉, 吴焕文, 梁智勇. 双向调节蛋白与肿瘤的相关性研究进展[J]. 临床与病理杂志, 2016, 1:71-75.
[14]	HE X, WANG L, RIEDEL H, et al. Mesothelin promotes epithelial-to-mesenchymal transition and tumorigenicity of human lung cancer and mesothelioma cells[J]. Mol Cancer, 2017, 16(1):63. DOI PMID
[15]	BERASAIN C, AVILA M A. Amphiregulin[J]. Semin Cell Dev Biol, 2014, 28:31-41. DOI PMID
[16]	MADEIRA K, DONDOSSOLA E R, FARIAS B F, et al. Mesothelin as a biomarker for ovarian carcinoma:a meta-analysis[J]. An Acad Bras Cienc, 2016, 88(2):923-932. DOI URL
[17]	TAKIHATA Y, EINAMA T, KOBAYASHI K, et al. Different role of MSLN and CA125 co-expression as a prognostic predictor between perihilar and distal bile duct carcinoma[J]. Oncol Lett, 2021, 21(5):414. DOI PMID
[18]	CHAYANGSU C, KHUNSRI S, SRIURANPONG V, et al. The correlations between serum amphiregulin and other clinicopathological factors in colorectal cancer[J]. J Gastrointest Oncol, 2017, 8(6):980-984. DOI PMID
[19]	MELDERIS S, WARKOTSCH M T, DANG J, et al. The amphiregulin/EGFR axis protects from lupus nephritis via downregulation of pathogenic CD4+ T helper cell responses[J]. J Autoimmun, 2022, 129:102829. DOI URL

组别	例数	AREG/（ng·mL^-1）	MSLN/（ng·mL^-1）
健康对照组	35	219.8±81.2	0.425 1±0.234 0
良性病变组	38	274.6±93.8	0.481 4±0.244 5
乳腺癌组	54	318.6±106.4^*	0.561 9±0.313 6^*#

组别	例数	AREG/（ng·mL^-1）	MSLN/（ng·mL^-1）
健康对照组	35	219.8±81.2	0.425 1±0.234 0
良性病变组	38	274.6±93.8	0.481 4±0.244 5
乳腺癌组	54	318.6±106.4^*	0.561 9±0.313 6^*#

项目	敏感性/%	特异性/%	AUC（95%可信区间）
AREG	72	56	0.582（0.453~0.710）
MSLN	51	66	0.637（0.513~0.760）
CEA	76	68	0.657（0.541~0.773）
CA15-3	57	71	0.571（0.459~0.704）
联合检测	66	81	0.757（0.649~0.865）

项目	敏感性/%	特异性/%	AUC（95%可信区间）
AREG	72	56	0.582（0.453~0.710）
MSLN	51	66	0.637（0.513~0.760）
CEA	76	68	0.657（0.541~0.773）
CA15-3	57	71	0.571（0.459~0.704）
联合检测	66	81	0.757（0.649~0.865）

临床病理特征	例数	AREG/ （ng·mL^-1）	MSLN/ （ng·mL^-1）	临床病理特征	例数	AREG/ （ng·mL^-1）	MSLN/ （ng·mL^-1）
年龄				淋巴转移
<50岁	24	121.0±80.6	0.38（0.29，0.50）	有	16	321.7±114.1	0.50（0.34，0.89）
≥50岁	30	295.0±256.8	0.39（0.28，0.39）	无	38	256.0±95.9	0.33（0.27，0.43）
P值		0.060 0	0.644 0	P值		0.037 8	0.022 4
病理类型				雌激素受体
原位癌	17	269.5±70.2	0.32（0.29，0.48）	阳性	32	278.6±94.2	0.37（0.30，0.55）
浸润性癌	37	352.2±102.8	0.67（0.40，0.93）	阴性	22	283.9±147.2	0.39（0.26，0.62）
P值		0.006 1	0.006 0	P值		0.886 4	0.764 1
脉管侵犯				孕激素受体
无	35	272.3±91.3	0.38（0.28，0.62）	阳性	29	285.5±92.9	0.39（0.32，0.62）
有	19	287.1±125.6	0.43（0.32，0.67）	阴性	25	261.7±141.6	0.36（0.28，0.59）
P值		0.591 8	0.497 4	P值		0.592 1	0.512 4
TNM分期				人表皮生长因子受体2
Ⅰ~Ⅱ期	30	272.3±91.3	0.39（0.25，0.50）	0	8	275.2±50.3	0.38（0.26，0.62）
Ⅲ~Ⅳ期	24	287.1±125.6	0.39（0.30，0.70）	+	26	279.3±89.9	0.39（0.29，0.51）
P值		0.633 3	0.399 4	++	9	289.5±90.1	0.48（0.31，0.73）
				+++	11	282.2±72.7	0.38（0.25，0.86）
				P值		0.409 8	0.928 4