血清SBEM、hMAM和CEACAM19水平在乳腺癌早期诊断中的临床意义

doi:10.13481/j.1671-587X.20210623

Abstract

Abstract: Objective

To detect the levels of small breast epithelial mucin （SBEM），human mammaglobin（hMAM），and carcinoembryonic antigen-related cell adhesion molecule 19（CEACAM19） in serum of the patients with breast cancer， and to clarify the significances of these indicators in the early diagnosis of breast cancer and their relationships with the clinicopathological parameters of the patients.

Methods

A total of 80 patients with breast cancer were selected as breast cancer group， 58 patients with benign breast disease were selected as benign breast disease group， and 54 healthy women were selected as healthy control group. The serum levels of SBEM， hMAM，and CEACAM19 of the subjects in three groups were measured by ELISA method.The receiver operating characteristic curve（ROC） was used to analyze the area under curve （AUC），cut-off value， sensitivity and specificity of these indexes in diagnosis of breast cancer.

Results

The levels of serum SBEM， hMAM，and CEACAM19 of the patients in breast cancer group were significantly higher than those in benign breast lesion group and healthy control group （P<0.05）. Compared with TNM Ⅰ-Ⅱ stages， the levels of serum SBEM， hMAM，and CEACAM19 in the patients with TNM Ⅲ-Ⅳ stages breast cancer were significantly increased （P<0.05）.Compared with negative lymph node metastasis group， the serum levels of SBEM， hMAM，and CEACAM19 in the breast cancer patients with positive lymphnode metastasis were significantly increased （P<0.05）.The AUC， sensitivities，and specificities of SBEM， hMAM， CEACAM19 and SBEM+hMAM+CEACAM19 in diagnosis of the breast cancer were 0.868， 80.0% and 88.4%； 0.809， 70.0% and 80.4%； 0.756， 97.5% and 50.9%； 0.913， 82.5% and 90.2%.The combined detection had the best diagnotic efficiency.

Conclusion

The combined detection of serum SBEM， hMAM and CEACAM19 has high sensitivity and specificity in diagnosis of the breast cancer， which can improve the early diagnotic efficiency of the breast cancer patients.

Key words: breast neoplasms, small breast epithelial mucin, human mammaglobin, carcinoembryonic antigen-related cell adhesion molecule 19

CLC Number:

R737.9

Xiuyan YU,Chunying TIAN,Xiaowei ZHANG,Xuefeng WU. Clinical significances of serum levels of SBEM, hMAM and CEACAM19 in early diagnosis of breast cancer[J].Journal of Jilin University(Medicine Edition), 2021, 47(6): 1518-1525.

Figures/Tables 4

Tab.1

Fig.1

Tab. 2

Tab. 3

Relationships between levels of SBEM, hMAM,and CEACAM19 in serum and clinicopathological parameters of breast cancer patients"

Clinicopathological feature	n	SBEM［ρ_B/(μg·L^-1)］	Z/P	hMAM［ρ_B/(ng·L^－1)］	Z/P	CEACAM19［ρ_B/(ng·L^－1)］	Z/P
Age(year)
≤50	35	7.58(4.14,14.33)	0.524/0.600	200.86(117.83,282.30)	0.301/0.764	97.70(71.70,150.60)	0.698/0.485
>50	45	7.54(4.82,10.82)	0.524/0.600	198.45(147.29,273.34)	0.301/0.764	82.80(63.29,149.83)	0.698/0.485
Maximum tumor size (l/cm)
≤2	43	6.79(3.33,10.75)	1.882/0.060	179.85(119.86,263.00)	1.501/0.133	78.40(59.50,112.20)	2.186/0.029
>2	37	10.41(4.97,13.81)	1.882/0.060	206.62(147.29,288.56)	1.501/0.133	99.80(73.26,159.50)	2.186/0.029
TNM stage
Ⅰ-Ⅱ	80	6.42(3.21,10.63)	5.420/<0.001	168.99(116.50,249.93)	3.621/<0.001	76.69(60.23,98.11)	4.903/<0.001
Ⅲ-Ⅳ	22	15.35(10.57,22.67)	5.420/<0.001	262.36(200.26,294.90)	3.621/<0.001	155.33(113.18,183.98)	4.903/<0.001
Lymphnode metastasis
Yes	45	5.59(2.27,10.69)	3.283/0.001	175.83(118.84,267.18)	1.989/0.048	82.50(68.47,100.90)	1.999/0.045
No	35	10.68(6.86,17.01)	3.283/0.001	238.63(168.99,284.03)	1.989/0.048	142.20(67.20,164.50)	1.999/0.045
ER
Negtive	16	9.15(6.86,10.57)	0.217/0.829	161.24(107.36,194.19)	0.210/0.833	78.28(68.71,146.91)	0.932/0.351
Positive	64	11.41(5.85,14.40)	0.217/0.829	192.58(119.35,225.65)	0.210/0.833	79.64(63.29,163.77)	0.932/0.351
PR
Negtive	20	7.88(6.75,10.52)	0.372/0.710	187.60(114.73,193.80)	0.622/0.534	72.24(61.68,126.05)	0.022/0.982
Positive	60	12.40(5.28,14.58)	0.372/0.710	197.55(118.84,245.11)	0.622/0.534	82.80(65.25,164.01)	0.022/0.982
Her-2
Negtive	64	10.52(6.45,14.12)	0.427/0.669	179.07(118.34,206.08)	0.872/0.383	83.57(67.93,164.26)	0.577/0.564
Positive	16	8.70(6.99,10.41)	0.427/0.669	191.09(187.60,194.57)	0.872/0.383	61.68(55.83,67.53)	0.577/0.564
Ki-67
Negtive	14	10.32(6.42,14.23)	1.488/0.137	83.66(49.50,117.83)	1.557/0.119	65.25(63.29,67.20)	0.798/0.425
Positive	66	10.41(6.64,13.46)	1.488/0.137	193.80(123.77,206.08)	1.557/0.119	83.57(68.18,164.26)	0.798/0.425
AR
Negtive	6	7.20(6.52,7.88)	0.845/0.398	114.73(100.00,129.46)	0.804/0.422	78.28(72.24,84.33)	0.124/0.902
Positive	31	10.52(6.56,14.12)	0.845/0.398	193.80(120.36,206.08)	0.804/0.422	79.64(64.27,164.26)	0.124/0.902
P53
Negtive	20	10.41(3.73,13.31)	1.102/0.270	193.02(115.17,201.65)	1.365/0.172	67.53(63.29,120.49)	2.520/0.012
Positive	14	10.41(7.44,14.36)	1.102/0.270	187.60(124.66,314.81)	1.365/0.172	89.00(77.52,166.71)	2.520/0.012
EGFR
Negtive	21	10.52(6.87,14.40)	1.606/0.108	190.31(119.35,205.86)	0.887/0.375	80.40(66.47,163.77)	0.571/0.568
Positive	10	7.45(1.67,11.44)	1.606/0.108	160.16(67.59,345.41)	0.887/0.375	75.00(64.27,229.64)	0.571/0.568
P63
Negtive	28	7.71(4.73,11.27)	0.913/0.361	163.81(113.85,203.70)	0.723/0.470	77.41(63.29,127.13)	1.104/0.270
Positive	8	11.69(4.74,16.08)	0.913/0.361	234.91(97.09,280.53)	0.723/0.470	96.61(70.37,178.54)	1.104/0.270

Tab. 3

References 30

1	ZISI Z， ADAMOPOULOS P G， KONTOS C K， et al. Identification and expression analysis of novel splice variants of the human carcinoembryonic antigen-related cell adhesion molecule 19 （CEACAM19） gene using a high-throughput sequencing approach［J］. Genomics， 2020， 112（6）： 4268-4276.
2	MICHAELIDOU K， TZOVARAS A， MISSITZIS I， et al. The expression of the CEACAM19 gene， a novel member of the CEA family， is associated with breast cancer progression［J］.Int J Oncol， 2013，42（5）：1770-1777.
3	ESTIAR M A， ESMAEILI R， ZARE A A， et al. High expression of CEACAM19， a new member of carcinoembryonic antigen gene family， in patients with breast cancer［J］. Clin Exp Med， 2017， 17（4）： 547-553.
4	MIKSICEK R J， MYAL Y， WATSON P H， et al. Identification of a novel breast-and salivary gland-specific， mucin-like gene strongly expressed in normal and tumor human mammary epithelium［J］. Cancer Res， 2002， 62（10）： 2736-2740.
5	LI Q H， LIU Z Z， GE Y A， et al. Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial‑to‑mesenchymal transition［J］. Oncol Rep， 2020， 44（2）： 509-518.
6	ZHANG Y Q， LUN X Q， GUO W L. Expression of TRPC₁ and SBEM protein in breast cancer tissue and its relationship with clinicopathological features and prognosis of patients［J］. Oncol Lett， 2020， 20（6）： 392.
7	KIM S W， GOEDEGEBUURE P， GILLANDERS W E.Mammaglobin-A is a target for breast cancer vaccination［J］.Oncoimmunology，2016，5（2）：e1069940.
8	OLOOMI M， MOAZZEZY N， BOUZARI S. Modulation of molecular biomarker expression in response to chemotherapy in invasive ductal carcinoma［J］. Biomed Res Int， 2018， 2018： 7154708.
9	NGUYEN H M， DAO M Q. Detection of human mammaglobin mRNA in breast cancer cells among Vietnamese women［J］. Breast Cancer （Dove Med Press）， 2019， 11： 143-150.
10	BAKER L， HALL L， WILSON D， et al. Plasma levels of mammaglobin-A， VEGF and PlGF in human breast cancer pathology and survival［J］. Eur J Surg Oncol， 2019， 45（2）： e40.
11	GHASEMI-DEHKORDI P， DOOSTI A， JAMI M S. The functions of azurin of Pseudomonas aeruginosa and human mammaglobin-A on proapoptotic and cell cycle regulatory genes expression in the MCF-7 breast cancer cell line［J］. Saudi J Biol Sci， 2020， 27（9）： 2308-2317.
12	崔云会，陈楠，王云龙，等. 人乳腺珠蛋白荧光免疫层析检测方法的建立［J］.中国免疫学杂志，2021，37（8）： 975-978.
13	于秀艳，张晓伟，野丽莉，等. hMAM联合MMP-9和C-erbB2 mRNA表达检测在乳腺癌外周血微转移诊断中的应用［J］.吉林大学学报（医学版），2017，43（5）：1009-1014.
14	于秀艳，张晓伟，丛占杰，等. 乳腺癌患者血清中hMAM和CD147水平检测及其临床意义［J］. 吉林大学学报（医学版）， 2018， 44（6）： 1269-1274.
15	乳腺癌雌、孕激素受体免疫组织化学检测指南编写组. 乳腺癌雌、孕激素受体免疫组织化学检测指南［J］．中华病理学杂志，2015，44（4）： 237-239.
16	《乳腺癌HER检测指南》编写组，霍临明. 乳腺癌HER2检测指南［J］. 中华病理学杂志，2006，35（10）： 631-633.
17	许良中，杨文涛. 免疫组织化学反应结果的判断标准［J］. 中国癌症杂志， 1996， 6（4）：229-231.
18	CASTELLANO I， ALLIA E， ACCORTANZO V，et al.Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers［J］. Breast Cancer Res Treat， 2010， 124（3）： 607-617.
19	NIELL B L， FREER P E， WEINFURTNER R J，et al. Screening for breast cancer［J］. Radiol Clin North Am， 2017， 55（6）： 1145-1162.
20	BRITT K L， CUZICK J， PHILLIPS K A. Key steps for effective breast cancer prevention［J］. Nat Rev Cancer， 2020， 20（8）： 417-436.
21	CHEN I X， CHAUHAN V P， POSADA J， et al. Blocking CXR4 alleviates desmoplasia，increases T-lymphocyte infltration，and improves immunotherapy in meta-static breast cancer［J］.Proc Natl Acad Sci U S A，2019，116（10）：4558-4566.
22	BAKER E， WHITEOAK N， HALL L， et al. Mammaglobin-A， VEGFR3， and Ki67 in human breast cancer pathology and five year survival［J］. Breast Cancer， 2019， 13： 1178223419858957.
23	MILOSEVIC M， JANKOVIC D， MILENKOVIC A， et al. Early diagnosis and detection of breast cancer［J］. Technol Heal Care， 2018， 26（4）： 729-759.
24	KELLEHER M， SINGH R， O'DRISCOLL C M，et al. Carcinoembryonic antigen （CEACAM） family members and Inflammatory Bowel Disease［J］. Cytokine Growth Factor Rev， 2019， 47： 21-31.
25	JOUDI F SAL. Human mammaglobin in breast cancer： a brief review of its clinical utility［J］. Indian J Med Res， 2014， 139（5）： 675-685.
26	SKLIRIS G P， HUBÉ F， GHEORGHIU I， et al. Expression of small breast epithelial mucin （SBEM） protein in tissue microarrays （TMAs） of primary invasive breast cancers［J］.Histopathology，2008，52（3）：355-369.
27	于洪涛，唐大海. 癌胚抗原相关细胞粘附因子19与乳腺癌相关基因关系［J］. 中国公共卫生， 2016， 32（1）： 105-107.
28	LI J， XU W W， ZHU Y X. Mammaglobin B may be a prognostic biomarker of uterine corpus endometrial cancer［J］. Oncol Lett， 2020， 20（5）： 255.
29	卢达新，高艳霞，于丽凤，等.微小RNA hsa-mir-301b对乳腺癌细胞增殖能力的影响研究［J］.中国实用内科杂志，2021，41（2）：141-145.
30	ZHAO H， XU J， WANG Y， et al. Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of PI3K/Akt and NF-κB［J］. Surg Oncol， 2018， 27（3）： 495-502.

Group	n	SBEM［(ρ_B/(μg·L^－1)］	hMAM［(ρ_B/(ng·L^－1)］	CEACAM19［(ρ_B/(ng·L^－1)］
Healthy control	54	0.63(0.32,1.43)	106.20(67.45,138.57)	36.84(21.64,95.88)
Benign breast disease	58	2.91(1.58,3.78)	103.10(70.73,158.98)	49.18(31.59,83.33)
Breast cancer	80	7.56(4.51,11.30)^*△	200.63(136.05,275.95)^*△	86.50(67.28,148.83)^*△

[1]	Xiuyan YU,Ting LI,Zhanjie CONG,Wenlong WANG,Xiaowei ZHANG,Xuefeng WU. Combined detection of hMAM, SBEM and CEACAM19 mRNA in peripheral blood of breast cancer patients and its clinical significance [J]. Journal of Jilin University(Medicine Edition), 2022, 48(1): 195-202.
[2]	Yang YU,Sainan LIU,Yunkai LIU,Yong LI,Yichun QIAO,Yi CHENG. Bioinformatic analysis on expression characteristics of PRPS2 and its relationship with prognosis of breast cancer [J]. Journal of Jilin University(Medicine Edition), 2021, 47(5): 1229-1236.
[3]	Qing WANG,Siqi XIE,Kai ZHENG,Yiyin TANG,Hongwan LI,Hengyu ZHANG,Mingjian TAN,Lei PENG,Dequan LIU,Shicong TANG. Detection of serum vitamin-B levels in breast cancer patients receiving different chemotherapy regimens and its clinical significance [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 724-730.
[4]	Haoxuan TANG,Nanfeng MENG,Meiling DU,Wei WANG,Tao HE. Inhibitory effect of new VEGF monoclonal antibody combined with all-trans retinoic acid on proliferation of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 344-351.
[5]	KONG Wencong, HE Wubin, SU Rongjian, JIA Daqi, GU Yanjiao, WANG Yue, DU Xiaoyuan. Inhibitory effect and apoptosisinduction of MST1R inhibitor BMS-777607 on proliferation of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2020, 46(03): 451-457.
[6]	CHEN Zhouhua, GONG Hui, FENG Lei, XIAO Yujie, HUANG Lizhong. Induction of LPS on epithelial mesenchymal transition in breast cancer MDA-MB-231 cells and its effect on β-catenin expression [J]. Journal of Jilin University(Medicine Edition), 2020, 46(02): 309-315.
[7]	ZHOU Chun, WANG Guanghua, ZHANG Bangzhu. Effects of miR-367 on proliferation, invasion and migration of human breast cancer MCF-7 cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1353-1360.
[8]	YANG Zhuangqing, LU Mei, YANG Xiaojuan, WANG Chang'an, ZOU Jieya. Inhibitory effect of inhibiting TRIM24 gene expression on proliferation, apopotosis,invasion and migration of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1379-1383.
[9]	YUE Yuan, XU Yinglian, WANG Jingjing, SUN Minying, ZHANG Zenan, ZHAO Xinyue, LI Zongpu, TAI Guixiang. Inhibitory effects of down-regulation of JNK enzymatic activity on growth of human prostate cancer cells, hepatocellular carcinoma cells and breast cancer cells [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1046-1051.
[10]	YU Xiuyan, WAN Guangcai, SUN Hongshuai, ZHU Hua, GAO Haiyan, WU Xuefeng. Relationship between fibrinogen and prognosis of breast cancer patients:A Meta-analysis [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1092-1097.
[11]	TAN Qi, REN Liqun, ZHANG Yibing, WANG Yadi, GU Zehui, HUANG Peng, CHEN Suxian. Application of bioinformatics in screening of miRNA biomarkers in triple-negative breast cancer [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1098-1105.
[12]	WANG Shuang, KANG Lihua, GUAN Meng, WANG Lei, LI Beibei, ZHAO Yue, SONG Yanqiu, YANG Tingting. Clinical application of apatinib mesylate combined with chemotherapy in treatment of patients with advanced breast cancer [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1152-1158.
[13]	XIN Rui, LI Dong, XU Huiying, WANG Chunyu, QU Danhua, SUN Haifeng. Influence of miRNA-21 in radiosensitivity of breast cancer cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2019, 45(04): 772-778.
[14]	ZHOU Hongxu, DU Ye, YU Yunhe, HAN Bing, LI Sijie, GUO Guoqiang, FAN Zhimin. Discordance for hormone receptors and Her-2 expressions in primary lesion and ipsilateral axillary lymph node metastasis of breast cancer and its influence in prognosis [J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 376-382.
[15]	SHANG Yanhong, PAN Yuchen, JIA Zhifang, WANG Yueqi, YANG Na, ZHAO Dan, JIANG Jing. Detection of expression levels of miR200 family in plasma of breast cancer patients and its significance [J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 383-388.

Clinical significances of serum levels of SBEM, hMAM and CEACAM19 in early diagnosis of breast cancer

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 30

Related Articles 15

Metrics

Comments

Recommended 10

Item	AUC	Sensitivity(η/%)	Specificity(η/%)	Cut-off value	AUC
SBEM	0.868	80.0	88.4	4.05 μg·L^－1	0.809－0.926
hMAM	0.809	70.0	80.4	158.87 μg·L^－1	0.747－0.871
CEACAM19	0.756	97.5	50.9	48.23 μg·L^－1	0.689－0.823
SBEM+hMAM+CEACAM19	0.913	82.5	90.2	－	0.869－0.958