Musashi2在不同分子分型乳腺浸润性导管癌中的表达及临床意义

doi:10.11958/20220121

天津医药 ›› 2022, Vol. 50 ›› Issue (9): 907-911.doi: 10.11958/20220121

Musashi2在不同分子分型乳腺浸润性导管癌中的表达及临床意义

平静¹(), 周东华¹, 朱大江², 田杰¹, 陈莹¹, 范菊花¹

1 佛山市妇幼保健院病理科（邮编528000）
2 乳腺疾病防治中心

收稿日期:2022-01-21 修回日期:2022-05-11 出版日期:2022-09-15 发布日期:2022-09-05
作者简介:平静（1981）,男,副主任医师,主要从事乳腺及妇科肿瘤方面研究。E-mail： pingjingyx@qq.com
基金资助:
广东省医学科研基金资助项目(A2019172)

Expression and its clinical significance of Musashi2 in different molecular subtypes of breast invasive ductal carcinoma

PING Jing¹(), ZHOU Donghua¹, ZHU Dajiang², TIAN Jie¹, CHEN Ying¹, FAN Juhua¹

1 Department of Pathology, Foshan Women and Children Hospital, Foshan 528000, China
2 Breast Disease Prevention and Control Center, Foshan Women and Children Hospital, Foshan 528000, China

Received:2022-01-21 Revised:2022-05-11 Published:2022-09-15 Online:2022-09-05

平静, 周东华, 朱大江, 田杰, 陈莹, 范菊花. Musashi2在不同分子分型乳腺浸润性导管癌中的表达及临床意义[J]. 天津医药, 2022, 50(9): 907-911.

PING Jing, ZHOU Donghua, ZHU Dajiang, TIAN Jie, CHEN Ying, FAN Juhua. Expression and its clinical significance of Musashi2 in different molecular subtypes of breast invasive ductal carcinoma[J]. Tianjin Medical Journal, 2022, 50(9): 907-911.

摘要/Abstract

摘要：

目的探讨Musashi2在不同分子分型乳腺浸润性导管癌中的表达及其与临床和分子病理特征及预后的相关性。方法收集125例乳腺浸润性导管癌患者的临床病理资料,采用免疫组织化学法检测肿瘤组织Musashi2、雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体-2（HER2）和Ki67表达,对HER2检测结果为“++”的病例进一步做荧光原位杂交（FISH）检测,依据检测结果进行分子分型,分析Musashi2表达与不同分子分型乳腺浸润性导管癌临床和分子病理特征及预后的关系。结果 Musashi2在乳腺浸润性导管癌和导管原位癌中的阳性率明显高于正常乳腺组织（P<0.01）。在Luminal A型和Luminal B型中的阳性率明显高于HER2过表达型和三阴型（P<0.01）。在TNM分期的早期（Ⅰ+Ⅱ期）患者的阳性率明显高于晚期（Ⅲ+Ⅳ期）患者（P<0.05）,但在不同年龄、肿瘤直径、组织学分级,脉管是否受累和淋巴结有无转移的乳腺润性导管癌,Musashi2的表达差异无统计学意义（P>0.05）。Musashi2表达水平与ER、PR呈显著正相关（r分别为0.408和0.405,P<0.05）,与HER2和Ki67无关（P>0.05）。Kaplan-Meier生存分析表明Musashi2阳性组和阴性组术后无病生存时间差异无统计学意义[（67±12）个月vs. （63±15）个月,Log-rank χ²=0.752,P>0.05]。结论 Musashi2蛋白在乳腺浸润性导管癌组织中的表达与其分子分型和TNM分期有关,Musashi2高表达提示肿瘤恶性程度较低。

关键词: 乳腺肿瘤, 癌,导管,乳腺, 病理学,临床, Musashi2

Abstract:

Objective To investigate the expression of Musashi2 in different molecular subtypes of breast invasive ductal carcinoma and its correlation with clinical and molecular pathological features and prognosis. Methods The clinicopathological data of 125 patients with breast invasive ductal carcinoma were collected. The expression of Musashi2, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2) and Ki67 expression in tumor tissues were detected by immunohistochemistry. Fluorescence in situ hybridization (FISH) was further detected in patients with a "++" HER2 immunohistochemistry results. According to the test results, molecular subtyping was performed. The relationship between Musashi2 expression and its clinical and molecular pathological characteristics and prognosis was analyzed in breast invasive ductal carcinoma with different molecular subtypes. Results The positive rates of Musashi2 in invasive ductal carcinoma and ductal carcinoma in situ were significantly higher than those in normal breast tissues (P<0.01). The positive rates in the Luminal A and the Luminal B groups were significantly higher than that in the HER2+ and triple-negative type groups (P<0.05). The positive rates of Musashi2 in early stage (Ⅰand Ⅱ) were significantly higher than those in the late stage (Ⅲ and Ⅳ, P<0.05). However, there were no significant differences in Musashi2 expression levels between different ages, tumor diameters, histological grades, vascular involvement and lymph node metastasis of invasive ductal carcinoma of breast (P>0.05). The expression level of Musashi2 was positively correlated with ER and PR (r = 0.408, r = 0.405), but no relationship with HER2 and Ki67 (P>0.05). Kaplan-Meier survival analysis showed that there was no significant difference in disease-free survival between the Musashi2 positive group and the Musashi2 negtive group (67 months±12 months vs. 63 months±15 months, Log-rank χ²=0.752, P>0.05). Conclusion The expression of Musashi2 protein in breast invasive ductal carcinoma is related to its molecular subtype and TNM stage. The higher expression of musashi2 indicates a lower degree of malignant.

Key words: breast neoplasms, carcinoma,ductal,breast, pathology,clinical, Musashi2

中图分类号:

R737.9

图/表 4

图1 乳腺癌不同组织免疫组织化学染色及荧光原位杂交 A：Musashi2在乳腺浸润性导管癌组织中阳性表达（×100）;B：Musashi2在乳腺导管原位癌组织中阳性表达（×100）;C：Musashi2在正常乳腺组织中阴性表达（×100）;D：乳腺浸润性导管癌HER-2基因成簇扩增（FISH,×1 000）。

Fig.1 Immunohistochemistry staining and fluorescence in situ hybridization of different tissues in breast cancer

表1 不同临床病理特征的乳腺浸润性导管癌患者Musashi2表达阳性率比较 [例（%）]

Tab.1 Comparison of positive expression rate of Musashi2 in invasive ductal carcinoma of breast between patients with different clinicopathological features

临床病理特征		n	Musashi2阳性	χ²
年龄（岁）	≤50	77	43（55.84）	0.075
	>50	48	28（58.33）	0.075
肿瘤直径（cm）	<2	50	32（64.00）	1.858
	2~5	66	34（51.52）
	>5	9	5（55.56）
脉管受累	否	84	46（54.76）	0.434
	是	41	25（60.98）	0.434
淋巴结转移	阴性	53	33（62.26）	1.120
	阳性	72	38（52.78）	1.120
TNM分期	早期	85	54（63.53）	4.902^＊
	晚期	40	17（42.50）	4.902^＊
组织学分级	Ⅰ+Ⅱ	101	61（60.40）	2.772
	Ⅲ	24	10（41.67）	2.772

表2 Musashi2表达与乳腺浸润性导管癌分子病理特征的关系 [例（%）]

Tab.2 The relationship between Musashi2 expression and molecular pathological features of breast invasive ductal carcinoma

项目		n	Musashi2阳性	χ²	r
HER-2	阴性	78	46（58.97）	0.400	-0.057
	阳性	47	25（53.19）	0.400	-0.057
ER	阴性	36	9（25.00）	20.837^＊＊	0.408^＊
	阳性	89	62（69.66）	20.837^＊＊	0.408^＊
PR	阴性	42	12（28.57）	20.541^＊＊	0.405^＊
	阳性	83	59（71.08）	20.541^＊＊	0.405^＊
Ki67	≤14%	29	20（68.97）	2.278	-0.135
	>14%	96	51（53.13）	2.278	-0.135

图2 Musashi2蛋白阴性和阳性乳腺浸润性导管癌患者生存曲线

Fig.2 Survival curves of Musashi2 protein negative and positive expressions in patients with breast invasive ductal carcinoma

参考文献 23

[1]	OKANO H, IMAI T, OKABE M. Musashi:a translational regulator of cell fate[J]. J Cell Sci, 2002, 115(Pt7):1355-1359. doi: 10.1242/jcs.115.7.1355.
[2]	李宇, 王鹏, 贾垚, 等. Msi2在上皮细胞肿瘤中的作用及临床价值[J]. 现代医学, 2017, 45(8):1167-1170.
	LI Y, WANG P, JIA Y, et al. Clinical value and role of Msi2 in epithelial tumor[J]. Modern Medical Journal, 2017, 4(8):1167-1170. doi: 10.3969/j.issn.1671-7562.2017.08.026.
[3]	李捷, 刘紫蒙, 郑一琼, 等. 乳腺浸润性导管癌组织IRS1、PRSS3蛋白表达与磷酸化蛋白激酶B表达和预后的关系研究[J]. 现代生物医学进展, 2021, 21(24):4617-4622.
	LI J, LIU Z M, ZHENG Y Q, et al. Relationship research between the IRS1,PRSS3 protein expression and phosphorylated protein kinase B expression and prognosis in breast invasive ductal carcinoma[J]. Progress in Modern Biomedicine, 2021, 21(24):4617-4622. doi: 10.13241/j.cnki.pmb.2021.24.003.
[4]	马建萍, 马芬兰. 不同分子分型乳腺癌的临床病理特征及预后的关系[J]. 实用癌症杂志, 2017, 32(12):2041-2044.
	MA J P, MA F L. Clinicopathological features and prognosis of different molecular types of breast cancer[J]. The Practical Journal of Cancer, 2017, 32(12):2041-2044. doi: 10.3969/j.issn.1001-5930.2017.12.039.
[5]	LAKHANI S R, ELLIS I O, SCHNITT S J, et al. WHO classification of tumours of the breast[M]. 4th ed. Lyon: International Agency for Research on Cancer (IARC) press, 2012:34-38.
[6]	GIULIANO A E, EDGE S B, HORTOBAGYI G N. Eighth edition of the AJCC cancer staging manual:breast cancer[J]. Ann Surg Oncol, 2018, 25(7):1783-1785. doi: 10.1245/s10434-018-6486-6.
[7]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2015版)[J]. 中国癌症杂志, 2015, 25(9):692-754.
	Chinese Anti-Cancer Association, Committee of Breast Cancer Society. Guidelines and norms for diagnosis and treatment of breast cancer of Chinese Anti-cancer Association (2015 edition)[J]. China Oncol, 2015, 25(9):692-754. doi: 10.3969/j.issn.1007-3969.2015.09.010.
[8]	《乳腺癌HER2检测指南2014版》编写组. 乳腺癌HER2检测指南(2014版)[J]. 中华病理学杂志, 2014, 43(4):262-267.
	“Breast cancer HER2 detection gudelines (2014 edition)” Compilling Group. Breast cancer HER2 detection guidelines (2014 edition)[J]. Chin J Pathol, 2014, 43(4):262-267. doi: 10.3760/cma.j.issn.0529-5807.2014.04.012.
[9]	KUDINOV A E, KARANICOLAS J, GOLEMIS E A, et al. Musashi RNA-binding proteins as cancer drivers and novel therapeutic targets[J]. Clin Cancer Res, 2017, 23(9):2143-2153. doi: 10.1158/1078-0432.CCR-16-2728.
[10]	王小刚, 刘静, 郭庚, 等. MSI2生物学特性的研究进展[J]. 国际遗传学杂志, 2017, 40(4):228-232.
	WANG X G, LIU J, GUO G, et al. Research progress of the biological characteristics of MSI2[J]. International Journal of Genetics, 2017, 40(4):228-232.doi: 10.3760/cma.j.issn.1673-4386.2017.04.008.
[11]	DAS CHAGAS P F, BARONI M, BRASSESCO M S, et al. Interplay between the RNA binding-protein Musashi and developmental signaling pathways[J]. J Gene Med, 2020, 22(1):e3136. doi: 10.1002/jgm.3136.
[12]	LIU Y, FAN Y, WANG X, et al. Musashi-2 is a prognostic marker for the survival of patients with cervical cancer[J]. Oncol Lett, 2018, 15(4):5425-5432. doi: 10.3892/ol.2018.8077.
[13]	ZHAO J, ZHANG Y, LIU X S, et al. RNA-binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression[J]. Cancer Sci, 2020, 111(2):369-382. doi: 10.1111/cas.14280.
[14]	YANG Z, LI J, SHI Y, et al. Increased musashi 2 expression indicates a poor prognosis and promotes malignant phenotypes in gastric cancer[J]. Oncol Lett, 2019, 17(3):2599-2606. doi: 10.3892/ol.2019.9889.
[15]	SHENG W, DONG M, CHEN C, et al. Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein[J]. Oncotarget, 2017, 8(9):14359-14373. doi: 10.18632/oncotarget.8736.
[16]	张苏杰, 殷华奇, 叶雄俊, 等. Musashi-2在恶性肿瘤发生发展及诊疗靶点中的作用[J]. 协和医学杂志, 2017, 8(4):289-293.
	ZHANG S J, YIN H Q, YE X J, et al. Role of Musashi-2 in the occurrence and development and as the diagnostic and therapeutic target of malignant tumours[J]. Medical Journal of Peking Union Medical College Hospital, 2017, 8(4):289-293. doi: 10.3969/j.issn.1674-9081.2017.05.018.
[17]	EMADI-BAYGI M, NIKPOUR P, MOHAMMAD-HASHEM F, et al. MSI2 expression is decreased in grade II of gastric carcinoma[J]. Pathol Res Pract, 2013, 209(11):689-691. doi: 10.1016/j.prp.2013.07.008.
[18]	王琳, 沈佳丽, 熊世双, 等. JAG1和Notch3在乳腺癌组织中的表达及预后价值[J]. 临床肿瘤学杂志, 2020, 25(1):13-19.
	WANG L, SHEN J L, XIONG S S, et al. Expression of JAG1 and Notch3 in breast cancer tissues and their prognostic value[J]. Chinese Clinical Oncology, 2020, 25(1):13-19. doi: 10.3969/j.issn.1009-0460.2020.01.003.
[19]	SORLIE T, TIBSHIRANI R, PARKER J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets[J]. Proc Natl Acad Sci U S A, 2003, 100(14):8418-8423. doi: 10.1073/pnas.0932692100.
[20]	KATZ Y, LI F, LAMBERT N J, et al. Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state[J]. Elife, 2014, 3:e03915. doi: 10.7554/eLife.03915.
[21]	李菲菲. Musashi在乳腺发育和肿瘤发生中的功能与分子作用机制[D]. 北京: 中国农业大学, 2016.
	LI F F. The function and molecular mechanism of Musashi on mammary gland development and tumorigenesis[D]. Beijing: China Agricultural University, 2016.
[22]	张莹, 任占平, 张芫. Ki-67表达与乳腺癌分子分型及临床病理特征的关系[J]. 临床与实验病理学杂志, 2014, 30(11):1220-1223.
	ZHANG Y, REN Z P, ZHANG Y. Relationship between the expression of Ki-67 and molecular classification and clinical pathological features in breast cancerr[J]. J Clin Exp Pathol, 2014, 30(11):1220-1223. doi: 10.13315/j.cnki.cjcep.2014.11.005.
[23]	KANG M H, JEONG K J, KIM W Y, et al. Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer[J]. Oncogene, 2017, 36(12):1745-1752. doi: 10.1038/onc.2016.327.

Musashi2在不同分子分型乳腺浸润性导管癌中的表达及临床意义

Expression and its clinical significance of Musashi2 in different molecular subtypes of breast invasive ductal carcinoma

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 4

参考文献 23

相关文章 15

编辑推荐

Metrics

本文评价

[1]	朱刚明, 董永德, 朱瑞婷, 谭源满, 陶娟, 刘晓, 陈德成, 杨概. 磁共振弛豫时间定量成像预测乳腺浸润性导管癌分子亚型的价值[J]. 天津医药, 2024, 52(7): 770-774.
[2]	陈芷彦, 伍秋苑, 邓裕华, 周丹. 类器官技术在乳腺癌研究中的现状及应用[J]. 天津医药, 2024, 52(6): 668-672.
[3]	刘丹阳, 李永涛, 张海燕, 李林, 刘洋, 沈雷. 乳腺癌细胞条件培养基对骨髓间充质干细胞生物学行为的影响[J]. 天津医药, 2024, 52(5): 454-458.
[4]	谢皓冉, 李一浩, 刘成, 夏瑜婷, 裘圣蕾, 熊斌, 冯其贞. 医保DIP支付背景下乳腺癌腋窝淋巴结转移的预测因素探讨[J]. 天津医药, 2024, 52(11): 1193-1196.
[5]	吴海啸, 马文娟, 李之珺, 张超. 基于放射组学评估胸肌指数与乳腺癌骨转移患者预后关系的研究[J]. 天津医药, 2023, 51(9): 1007-1010.
[6]	杨娉娉, 张景, 陈红宇, 张淼, 周定安, 方文. 抑癌基因SASH1在乳腺癌中结合Vimentin并负性调节Vimentin的表达[J]. 天津医药, 2023, 51(9): 904-908.
[7]	赵津津, 王振宇, 马贞秀. circRASSF2靶向miR-1343-3p对乳腺癌MDA-MB-231细胞增殖和凋亡的影响[J]. 天津医药, 2023, 51(7): 713-717.
[8]	刘丹阳, 王璐璐, 何军, 姜杨, 李永涛, 张晓东, 李鹏辉, 沈雷. 乳腺癌细胞培养上清液促进人脂肪间充质干细胞迁移和增殖的机制探讨[J]. 天津医药, 2023, 51(11): 1153-1157.
[9]	张宇, 刘梁生, 马文娟, 韩敏, 朱鹰, 路红. 早期肿块型乳腺浸润性导管癌超声征象与分子分型的相关性研究[J]. 天津医药, 2022, 50(8): 853-858.
[10]	伊万萍, 马德寿. 高强度聚焦超声通过TRIF介导的ERK通路增强乳腺癌的顺铂化疗敏感性[J]. 天津医药, 2022, 50(7): 698-706.
[11]	杜伟娇张家丽于文文沈梦曹水. 乳腺癌髓系来源抑制细胞与外周血单核细胞的相关性及对预后的影响[J]. 天津医药, 2022, 50(7): 734-738.
[12]	陈佩贤, 陈凯, 周丹, 潘瑞琳, 叶国麟△, 陈小松, 苏逢锡. 前哨淋巴结阳性及全乳切除的乳腺癌患者非前哨淋巴结转移的术中预测模型[J]. 天津医药, 2022, 50(5): 533-538.
[13]	马小开, 郭飞, 朱金海, 朱林, 陈春春, 黄建康, 马宜传. CT三维重建在评估乳腺癌前哨淋巴结状态及其引流通路中的应用研究[J]. 天津医药, 2022, 50(3): 291-295.
[14]	陆旭阳, 刘奕, 李晓辉, 黄欣, 黄翠霞, 马书祥, 窦伟瑜, 谢彬彬, 曾麒燕. miR-1307-3p通过靶向ISM1促进乳腺癌细胞的增殖和迁移[J]. 天津医药, 2022, 50(2): 113-119.
[15]	苏亚静, 吴焕良, 敬波, 吴灿章. circMTO1调控Wnt/β-catenin抑制乳腺癌细胞增殖和转移能力的机制研究[J]. 天津医药, 2022, 50(11): 1134-1138.